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Information on EC 5.6.2.1 - DNA topoisomerase
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5.6.2.1 DNA topoisomeraseIUBMB Comments
These enzymes bring about the conversion of one topological isomer of DNA into another, e.g., the relaxation of superhelical turns in DNA, the interconversion of simple and knotted rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences, cf. EC 5.6.2.2 DNA topoisomerase (ATP-hydrolysing).
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Word Map
- 5.6.2.1
- camptothecins
-
supercoiled
- strand
- etoposide
-
poison
- topotecan
- irinotecan
- leukemia
- chromatin
-
cleavable
- doxorubicin
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single-stranded
- fluoroquinolones
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quinolone
- ovarian
- duplex
- colorectal
- ciprofloxacin
-
ii-mediated
- fork
- helicase
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schedule
- cisplatin
-
decatenation
-
antiproliferative
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checkpoint
-
superhelical
- novobiocin
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intercalation
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breakage
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dna-damaging
-
unwind
- neutropenia
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dose-limiting
-
s-phase
- anthracyclines
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cross-resistance
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myelosuppression
- kinetoplast
-
taxanes
- levofloxacin
-
nalidixic
- mitoxantrone
- scleroderma
-
rejoin
- analysis
- chk1
- medicine
- drug development
- aphidicolin
-
etoposide-induced
- pharmacology
-
holliday
- diagnostics
- norfloxacin
The enzyme appears in viruses and cellular organisms
Reaction Schemes
ATP-independent breakage of single-stranded DNA, followed by passage and rejoining
Synonyms
topoisomerase, topoisomerase i, topo i, dna topoisomerase i, topoisomerase iv, dna topoisomerase, topoisomerase 1, human topoisomerase i, reverse gyrase, topoisomerase-i, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ATP-independent type I topoisomerase
bcTopo IIIbeta
Dam DNA topoisomerase III
Deoxiribonucleate topoisomerase
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-
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Deoxiribonucleic topoisomerase
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DNA topoisomerase
DNA topoisomerase 1
DNA topoisomerase I
DNA topoisomerase IB
DNA topoisomerase III
belongs to the type IA family of DNA topoisomerases
DNA topoisomerase IIIalpha
EC 5.99.1.2
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formerly
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hTop1p
hTopoI
Isomerase, deoxiribonucleate topo-
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Late protein H6
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LdTopIIIbeta
MttopoI
Nicking-closing enzyme
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omega-Protein
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Relaxing enzyme
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Reverse gyrase
SiRe_1176
Swivelase
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Top1
TOP1alpha
TOP1mt
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Top1p
TopA
TopIB
Topo I
topoI
Topoisomerase
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topoisomerase 1
Topoisomerase I
topoisomerase IB
topoisomerase III
topoisomerase IIIbeta
TopR1
TpI
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Type I DNA topoisomerase
type IA DNA topoisomerase
type IA topoisomerase
Untwisting enzyme
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vTopo
DNA topoisomerase I
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hTopoI
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htopoI readily and very efficiently forms double cleavage complexes after the relaxation of negatively supercoiled plasmid DNA both with recombinant enzyme and with purified htopoI. When topo I is isolated from HeLa S3 cells, a considerable fraction migrates to the same gel electrophoretic position as topo I bearing a covalently bound 13-mer oligonucleotide. This may suggest that double cleavage complexes also form under intracellular conditions
Reverse gyrase
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Reverse gyrase
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is a DNA topoisomerase, specific to microorganisms living at high temperatures, which comprises a type IA topoisomerase fused to an SF2 helicase-like module and catalyzes ATP hydrolysis-dependent DNA positive supercoiling
Reverse gyrase
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is a DNA topoisomerase, specific to microorganisms living at high temperatures, which comprises a type IA topoisomerase fused to an SF2 helicase-like module and catalyzes ATP hydrolysis-dependent DNA positive supercoiling
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Top1
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Topo I
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Topo I
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Topoisomerase I
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Topoisomerase I
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Topoisomerase I
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677937, 678603, 679159, 681292, 681403, 681408, 681674, 682092, 682169, 682212, 691137, 691221, 691264, 691321, 691568, 691582, 691608, 692246, 692660, 693067, 693113, 693543, 702579, 702598, 702602, 702689, 702885, 703153, 705047, 705827, 705842, 705973, 714448, 714463, 714474, 714643, 714760, 714814, 714900, 714903, 715867, 716007, 716380, 726976, 727170, 727204, 727417, 728098, 728293, 728558, 728579, 728639, 728804
Topoisomerase I
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topoisomerase IIIbeta
subfamily of prokaryotic type IA topoisomerases that are different from the prototypical ecTopo I and ecTopo III-like enzymes
topoisomerase IIIbeta
subfamily of prokaryotic type IA topoisomerases that are different from the prototypical ecTopo I and ecTopo III-like enzymes
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Type I DNA topoisomerase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP-independent breakage of single-stranded DNA, followed by passage and rejoining
mechanism
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ATP-independent breakage of single-stranded DNA, followed by passage and rejoining
acts by directing a nucleophilic attack from the hydroxyl group of an internal Tyr into a phosphodiester bond in the DNA backbone, resulting in nicking of one strand of the DNA double helix and formation of a covalent linkage between the 3'-phosphate and the Tyr hydroxyl group
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ATP-independent breakage of single-stranded DNA, followed by passage and rejoining
alters the linking number in steps of one
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ATP-independent breakage of single-stranded DNA, followed by passage and rejoining
alters the linking number in steps of one
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ATP-independent breakage of single-stranded DNA, followed by passage and rejoining
enzyme closes its substrate DNA molecule after the removal of each superhelical turn, dissociation of the enzyme substrate complex may but does not necessarily occur after each cycle of the reaction
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ATP-independent breakage of single-stranded DNA, followed by passage and rejoining
bcTopo IIIbeta does not act on partially relaxed DNA. In contrast to ecTopo III Escherichia coli topoisomerase bcTopo IIIbeta can not further relax this substrate. bcTopo IIIbeta and ecTopo III exhibit comparable single stranded DNA binding activities and cleavage site specificities. bcTopo IIIbeta does not possess decatenation activity. Unlike ecTopo III, bcTopo III beta is not capable of decatenating replication intermediates
ATP-independent breakage of single-stranded DNA, followed by passage and rejoining
cleaves single-stranded DNA (ssDNA) via a 5' phosphotyrosine intermediate
ATP-independent breakage of single-stranded DNA, followed by passage and rejoining
demonstrated that human Topo I specifically stimulates the origin binding activity of PV E1, apparently through a protein-protein interaction. Topo I stimulates the origin binding activity of papillomavirus protein E1. Topo I stimulation of E1 binding is highly specific, verified by enzyme-linked immunosorbent assays using a nonorigin DNA fragment, Topo I stimulation of E1 DNA binding activity is origin specific. E1 does not affect the DNA binding activity of Topo I. DNA modulates the interaction between E1 and Topo I (ELISA-based protein interaction assays). Topo I and E2 stimulate the origin binding of E1 independently(enzyme-linked immunosorbent assay)
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ATP-independent breakage of single-stranded DNA, followed by passage and rejoining
Human topoisomerase I-mediated DNA relaxation reaction studied following modification of the enzyme at the active site tyrosine (position 723)
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ATP-independent breakage of single-stranded DNA, followed by passage and rejoining
Identification of proteins that bind nicked DNA intermediates formed in the course of base excision repair (BER) in cell free extracts of Saccharomyces cerevisiae. Using a photocrosslinking technique with photoactivable dNTP analogues to trap proteins that interact with damaged DNA. Top1 has the potential to interfere with base excision repair in vivo
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ATP-independent breakage of single-stranded DNA, followed by passage and rejoining
Vaccinia DNA topoisomerase (vTopo) catalyzes highly specific nucleophilic substitution at a single phosphodiester linkage in the pentapyrimidine recognition sequence 5'-(C/T)+5C4+C3+T+2T+1pN-1 using an active-site tyrosine nucleophile, thereby expelling a 5'hydroxyl leaving group of the DNA. Equilibrium binding and cleavage measurements. Cleavage reactions and modified substrates for vTopo, kinetic and thermodynamic parameters for variable length vTopo substrates with guanine base substitutions and deletions are shown
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ATP-independent breakage of single-stranded DNA, followed by passage and rejoining
catalytic mechanism of DNA cleavage/religation and molecular basis for selectivity of a cytosine base at the -4 position. E9 acts as a general base in DNA cleavage, assisted by charge relay through D111 and H365
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ATP-independent breakage of single-stranded DNA, followed by passage and rejoining
deprotonation of the 5' DNA end might be the limiting step in the topoisomerase religation mechanism
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ATP-independent breakage of single-stranded DNA, followed by passage and rejoining
mechanism of DNA relaxation for type IA topoisomerases, overview
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ATP-independent breakage of single-stranded DNA, followed by passage and rejoining
bcTopo IIIbeta does not act on partially relaxed DNA. In contrast to ecTopo III Escherichia coli topoisomerase bcTopo IIIbeta can not further relax this substrate. bcTopo IIIbeta and ecTopo III exhibit comparable single stranded DNA binding activities and cleavage site specificities. bcTopo IIIbeta does not possess decatenation activity. Unlike ecTopo III, bcTopo III beta is not capable of decatenating replication intermediates
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ATP-independent breakage of single-stranded DNA, followed by passage and rejoining
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
isomerization
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transesterification
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typ IB topoisomerases generate a tyrosyl-3'-phosphodiester. Recombinant MimiTopIB relaxes supercoiled DNA
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SYSTEMATIC NAME
IUBMB Comments
DNA topoisomerase
These enzymes bring about the conversion of one topological isomer of DNA into another, e.g., the relaxation of superhelical turns in DNA, the interconversion of simple and knotted rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences, cf. EC 5.6.2.2 DNA topoisomerase (ATP-hydrolysing).
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CAS REGISTRY NUMBER
COMMENTARY
80449-01-0
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(TTA)35
?
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trinucleotide repeat (TTA)35 lying in the intergenic region of chromosome XIII of Saccharomyces cerevisiae, between the RPM2 (RNase P mitochondrial 2) and PRE8 genes. This sequence contains the structural elements suitable to be susceptible to DNA topoisomerase I site-specific activity and to assemble nucleosomes. DNA topoisomerase I strongly recognizes the TTA repeats. The (TTA)35 repeat is engaged in a positioned nucleosome in vivo. DNA topoisomerase I efficiently reacts with the TTA repeat, the (TTA)35 sequence, the longest and most stable among the simple repeated sequences in Saccharomyces cerevisiae, is organized in a positioned nucleosome and this can possibly account for its high stability, in fact each nucleosome stores one negative supercoil, thus preventing DNA denaturation and induction of conformational alterations responsible for genetic instability. DNA topoisomerase I in vivo cleaves the (TTA)35 sequence after nucleosome removal, the positioned nucleosome on the (TTA)35 sequence represents a hindrance to the DNA topoisomerase I activity. This last conclusion, based on the glucose/galactose experiments, represents the first formal evidence that DNA topoisomerase I cannot react with nucleosomal DNA
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-
?
DNA
DNA
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so-called suicide substrate, contains a htopoI preferential binding sequence and is designed to trap the liberated 5'-OH end
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-
?
Holliday Junction Substrate H1-4
?
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close relationship between tyrosine recombinases and type IB topoisomerases, investigation of ability of human topoisomerase I to resolve the typical intermediate of recombinase catalysis, the Holliday junction, results consolidate the relationship between type IB topoisomerases and tyrosine recombinases
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?
negatively supercoiled pBlueScript KSII(+) DNA
relaxed pBlueScript KSII(+) DNA
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?
negatively supercoiled PUC18 DNA
?
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unable to relax positively supercoiled DNA
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?
supercoiled pBAD/Thio plasmid DNA
relaxced pBAD/Thio plasmid DNA
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?
DNA
?
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specific for single-stranded DNA, the enzyme drives extensive unwinding of closed circular DNA at high temperature. At 60-80°C it relaxes negatively but not positively supercoiled DNA. At 95°C, the enzyme unwinds both positively and negatively supercoiled substrates and produces extensively unwound form I* and I** DNA
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?
DNA
?
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specific for single-stranded DNA, the enzyme drives extensive unwinding of closed circular DNA at high temperature. At 60-80°C it relaxes negatively but not positively supercoiled DNA. At 95°C, the enzyme unwinds both positively and negatively supercoiled substrates and produces extensively unwound form I* and I** DNA
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?
DNA
?
the enzyme exhibits a very high DNA relaxing activity. Strong preference for a cytosine at position -4 of the cleavage
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?
DNA
?
the enzyme exhibits a very high DNA relaxing activity. Strong preference for a cytosine at position -4 of the cleavage
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?
negatively supercoiled DNA
?
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the activity of the protein in supercoil removal is limited and biphasic: in the first phase it progressively changes the linking-number of hypernegatively supercoiled DNA, but only to the superhelicity of a regular negative supercoil, in the second phase the enzyme relaxes the DNA further, but only slightly and slowly. The C-terminal 334 amino acids are unnecessary for activity, suggesting that this region, and perhaps the entire protein is involved in a function other than supercoil removal
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?
negatively supercoiled DNA
?
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the enzyme relaxes negatively supercoiled DNA in a distributive manner, leading to the total disappearance of the initial substrate and the appearance of intermediate topoisomers. The enzyme is able to cleave a single stranded oligonucleotide to bind covalently to the 5-end of cleaved DNA. The consensus sequence for DNA cleavage is CANNN-/-
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?
negatively supercoiled DNA
?
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ATP-independent relaxation of negatively supercoiled DNA. The lack of stimulation by ssDNA binding protein SSB suggests that ssDNA regions required for SsTop3 binding are stably exposed in the negatively supercoiled substrate at the high reaction temperature, even in the absence of ssDNA binding protein SSB
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?
negatively supercoiled DNA
relaxed DNA
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TopR1 can relax negative supercoils without ATP, while the extent of positive supercoiling catalyzed by TopR1 is dependent on the stoichiometry, the ATP concentration, the NaCl concentration and the assay temperature
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?
Nicked circular DNA
Large catenated DNA networks
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enzyme catalyzes: 1. linking or intertwining of covalently closed single-stranded DNA rings containing complementary base sequences, 2. formation of topological knots in single-stranded DNA rings, 3. catenation and decatenation of double-stranded DNA circles, if one of the reacting DNA molecules has a nick
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?
Nicked circular DNA
Large catenated DNA networks
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ColE1 DNA
which appear to rearrange to multimeric linear structures upon long incubation time
?
Nicked circular DNA
Large catenated DNA networks
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catenation reaction
which appear to rearrange to multimeric linear structures upon long incubation time
?
supercoiled DNA
?
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the enzyme relaxes supercoiled DNA starting from a certain point in the DNA molecules and proceeds in one direction towards one of the edges of the DNA molecule. The relaxation of the supercoiled DNA is subsequently followed by a knotting event
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?
supercoiled DNA
?
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reverse gyrase induces unwinding of synthetic four-way junctions as well as forked DNA substrates, following a mechanism independent of both the ATPase and the strand cutting activity of the enzyme. Reverse gyrase works like an ATP-independent helix-destabilizing protein specific for branched DNA structures
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?
supercoiled DNA
?
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reverse gyrase induces unwinding of synthetic four-way junctions as well as forked DNA substrates, following a mechanism independent of both the ATPase and the strand cutting activity of the enzyme. Reverse gyrase works like an ATP-independent helix-destabilizing protein specific for branched DNA structures
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?
supercoiled DNA
relaxed closed circular DNA
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removes superhelical turns from a negatively twisted DNA, no effect on positive superhelical turns
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?
supercoiled DNA
relaxed closed circular DNA
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positive and negative supercoiled DNA
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?
supercoiled DNA
relaxed closed circular DNA
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specific for negatively supercoiled DNA, no activity with positively supercoiled DNA
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?
supercoiled DNA
relaxed closed circular DNA
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specific for negatively supercoiled DNA, no activity with positively supercoiled DNA
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?
supercoiled DNA
relaxed closed circular DNA
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specific for negatively supercoiled DNA, no activity with positively supercoiled DNA
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?
supercoiled DNA
relaxed closed circular DNA
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relaxation
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?
supercoiled DNA
relaxed closed circular DNA
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specific for negatively supercoiled DNA, no activity with positively supercoiled DNA
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?
supercoiled DNA
relaxed closed circular DNA
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positive and negative supercoiled DNA
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?
supercoiled DNA
relaxed closed circular DNA
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positive and negative supercoiled DNA
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?
supercoiled DNA
relaxed closed circular DNA
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removes both positive and negative supercoils in steps of one
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?
supercoiled DNA
relaxed closed circular DNA
Drosophila sp. (in: flies)
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positive and negative supercoiled DNA
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?
supercoiled DNA
relaxed closed circular DNA
Drosophila sp. (in: flies)
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positive and negative supercoiled DNA
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?
supercoiled DNA
relaxed closed circular DNA
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specific for negatively supercoiled DNA, no activity with positively supercoiled DNA
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?
supercoiled DNA
relaxed closed circular DNA
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specific for negatively supercoiled DNA, no activity with positively supercoiled DNA
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?
supercoiled DNA
relaxed closed circular DNA
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specific for negatively supercoiled DNA, no activity with positively supercoiled DNA
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?
supercoiled DNA
relaxed closed circular DNA
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rather weak sequence specificity
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?
supercoiled DNA
relaxed closed circular DNA
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single-strand of DNA double helix
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?
supercoiled DNA
relaxed closed circular DNA
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relaxation of both negatively and positively supercoiled DNA circles
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?
supercoiled DNA
relaxed closed circular DNA
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positive and negative supercoiled DNA
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?
supercoiled DNA
relaxed closed circular DNA
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relaxation
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?
supercoiled DNA
relaxed closed circular DNA
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specific for negatively supercoiled DNA, no activity with positively supercoiled DNA
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?
supercoiled DNA
relaxed closed circular DNA
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cleavage sites on pNSI DNA
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?
supercoiled DNA
relaxed closed circular DNA
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rather weak sequence specificity
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?
supercoiled DNA
relaxed closed circular DNA
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negatively supercoiled plasmid pBR322 DNA
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?
supercoiled DNA
relaxed closed circular DNA
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positive and negative supercoiled DNA
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?
supercoiled DNA
relaxed closed circular DNA
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positive and negative supercoiled DNA
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?
supercoiled DNA
relaxed closed circular DNA
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positive and negative supercoiled DNA
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?
supercoiled DNA
relaxed closed circular DNA
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positive and negative supercoiled DNA
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?
supercoiled DNA
relaxed closed circular DNA
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negatively supercoiled plasmid pUC9 DNA
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?
supercoiled DNA
relaxed closed circular DNA
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relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
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negatively supercoiled plasmid pUC9 DNA
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?
supercoiled DNA
relaxed closed circular DNA
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positive and negative supercoiled DNA
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?
supercoiled DNA
relaxed closed circular DNA
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negatively supercoiled DNA
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?
supercoiled DNA
relaxed closed circular DNA
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relaxation
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?
supercoiled DNA
relaxed closed circular DNA
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negatively supercoiled DNA
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?
supercoiled DNA
relaxed closed circular DNA
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positive and negative supercoiled DNA
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?
supercoiled DNA
relaxed closed circular DNA
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negatively supercoiled plasmid DNA
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?
supercoiled DNA
relaxed closed circular DNA
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rather weak sequence specificity
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?
supercoiled DNA
relaxed closed circular DNA
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single-strand of DNA double helix
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?
supercoiled DNA
relaxed closed circular DNA
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positive and negative supercoiled DNA
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?
supercoiled DNA
relaxed closed circular DNA
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enzyme links to the 3' ends of the broken DNA strands
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?
supercoiled DNA
relaxed closed circular DNA
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relaxation
enzyme cannot rewind relaxed closed circular DNA
?
supercoiled DNA
relaxed closed circular DNA
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positive and negative supercoiled DNA
enzyme cannot rewind relaxed closed circular DNA
?
supercoiled DNA
relaxed closed circular DNA
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ColE1 DNA
enzyme cannot rewind relaxed closed circular DNA
?
supercoiled DNA
relaxed closed circular DNA
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relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
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relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
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positive and negative supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
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rather weak sequence specificity
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?
supercoiled DNA
relaxed closed circular DNA
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when oligonucleotide DNA duplexes are used as substrates, the generated cleavage complex contains an active enzyme, which is able to ligate the cleaved DNA to a variety of DNA fragments containing a free 5'-OH end
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?
supercoiled DNA
relaxed closed circular DNA
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single-strand of DNA double helix
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?
supercoiled DNA
relaxed closed circular DNA
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positive and negative supercoiled DNA
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?
supercoiled DNA
relaxed closed circular DNA
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positive and negative supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
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positive and negative supercoiled DNA
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?
supercoiled DNA
relaxed DNA
the enzyme relaxes the negative DNA supercoiling generated by RNA polymerase during transcription elongation
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-
?
additional information
?
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enzyme controls the topological state of DNA
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?
additional information
?
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role in control of DNA topology including regulation of supercoiling and maintenance of genetic stability
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?
additional information
?
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topoisomerase I works in concert with topoisomerase II to modulate the level of DNA supercoiling
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?
additional information
?
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DNA relaxation using supercoiled plasmid DNA pBR322 or pRYG
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?
additional information
?
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when enzyme expression is interfered with by a cognate double-stranded RNA injection, pleiotropic phenotypes with abnormalities in germ cell proliferation, oogenesis and embryogenesis appeare
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?
additional information
?
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when enzyme expression is interfered with by a cognate double-stranded RNA injection, pleiotropic phenotypes with abnormalities in germ cell proliferation, oogenesis and embryogenesis appeare
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?
additional information
?
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substrate is supercoiled pUC19 plasmid DNA. The enzyme contains a secondary DNA binding site located on the surface of the C-terminal domain, site architecture, overview. DNA binding mechanism and implications for TopIB-mediated DNA synapsis, modelling, detailed overview
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-
?
additional information
?
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Drosophila sp. (in: flies)
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enzyme controls the topological state of DNA
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-
?
additional information
?
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catalyzes the conversion of a paranemic to aplectonemic joint
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-
?
additional information
?
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enzyme catalyzes: 1. linking or intertwining of covalently closed single-stranded DNA rings containing complementary base sequences, 2. formation of topological knots in single-stranded DNA rings
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-
?
additional information
?
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phosphoryltosyl linkage between DNA and enzyme
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-
?
additional information
?
-
-
site-specific binding to DNA substrate, enzyme linkage to 5'-ends of DNA
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-
?
additional information
?
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enzyme changes conformation dramatically during the reaction cycle in order to accomplish these transformations. A 30000 Da fragment moves away from the rest of the protein to create an entrance into the central whole in the protein. This fragment can change conformation significantly. The fragment is composed of two domains, and while the domains themselves remain largely unchanged, their relative arrangement can change dramatically
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?
additional information
?
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-
enzyme changes conformation dramatically during the reaction cycle in order to accomplish these transformations. A 30000 Da fragment moves away from the rest of the protein to create an entrance into the central whole in the protein. This fragment can change conformation significantly. The fragment is composed of two domains, and while the domains themselves remain largely unchanged, their relative arrangement can change dramatically
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?
additional information
?
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enzyme controls the topological state of DNA
-
-
?
additional information
?
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the enzyme structure with bound DNA shows distinct conformational changes from the structure of the enzyme without bound DNA, overview. The portion of cleaved DNA 5' to the site of cleavage is anchored tightly with extensive noncovalent protein-DNA interactions. The portion of the oligonucleotide 5' to the cleavage site binds in a deep groove formed at the interface of domains I and III as well as within domain IV, in a similar orientation. Residues R195 and R321 are required for DNA cleavage
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-
?
additional information
?
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-
the strictly conserved arginine residue proximal to the active site tyrosine of type IA topoisomerases is required for the relaxation of supercoiled DNA. DNA cleavage can still take place in the absence of Arg231 function if Mg2+ is present to enhance the interaction of the enzyme with the scissile phosphate, but DNA rejoining is inhibited in the absence of this conserved arginine, resulting in accumulation of the cleaved covalent intermediate and loss of relaxation activity. In addition to the divalent metal ions, the side chain of this arginine residue is required for the precise positioning of the phosphotyrosine linkage for nucleophilic attack by the 3'-OH end to result in DNA rejoining
-
-
?
additional information
?
-
-
cleavage of 556 base single-stranded DNA substrate supercoiled pBAD/thio plasmid, and cleavage and religation of 59 base hairpin oligonucleotide substrates
-
-
?
additional information
?
-
-
relaxation and cleavage of pBR322 DNA, differences in the mechanism of these two related type IA topoisomerases, Topo I and Topo III, overview
-
-
?
additional information
?
-
-
single-molecule DNA relaxation assay, the pauses of the enzyme are short and the relaxation runs are slow
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-
?
additional information
?
-
-
topoisomerase I cleaves and rejoins one strand of double-stranded DNA to relax the negatively supercoiled DNA
-
-
?
additional information
?
-
-
a novel type of reaction is detected in the course of which an enzyme-attached single-stranded fragment is transferred and covalently ligated to the 5'-end of a separate double-stranded DNA molecule
-
-
?
additional information
?
-
-
enzyme promotes intertwining of complementary single-stranded DNA circles by forming relaxed duplex circles covalently closed in both strands. If denatured supercoiled PM2-DNA is used as a substrate, relaxed duplex circles as well as highly knotted molecules are seen among the products
-
-
?
additional information
?
-
-
enzyme becomes covalently linked to the 3'-phosphoryl group, when it cleaves DNA
-
-
?
additional information
?
-
-
controls the DNA topology by cleaving and rejoining DNA strands and passing other DNA strands through the transient gaps, plays a crucial role in the regulation of the physiological function of the genome
-
-
?
additional information
?
-
-
plays a crucial role in controlling the physiological functions of DNA
-
-
?
additional information
?
-
-
plays a direct role in the regulation of transcriptional initiation by acting as a repressor of the basal-level transcription
-
-
?
additional information
?
-
-
role of topoisomerase I in DNA replication, transcription and recombination
-
-
?
additional information
?
-
-
enzyme is unable to resolve topologically knotted circular duplex DNA
-
-
?
additional information
?
-
-
covalently binds double-stranded and single-stranded DNA forming an enzyme linked to the 3'-phosphoryl end and after binding to single-stranded DNA it can transfer the single-stranded donor DNA to an acceptor DNA possessing 5'-OH end groups
-
-
?
additional information
?
-
-
enzyme breaks down single-stranded DNA to smaller fragments. Each cleavage generates a free 5'-OH end and an enzyme-linked 3'-phosphoryl end
-
-
?
additional information
?
-
-
DNA structural alterations induced by UV lesions can be sufficient stimulus to induce cross-linking of topoisomerase I to cellular DNA
-
-
?
additional information
?
-
-
Topo I is the first endogenous interaction partner for c-Jun in the regulation of cancer cell proliferation. Topo I and JNK-c Jun pathway cooperate in the regulation of eGFR gene expression and in the proliferation of HT-1080 cells
-
-
?
additional information
?
-
-
only enzyme forms containing amino acids 203-765 can accurately control all steps of catalysis, particularly the DNA strand cleavage and the proposed controlled rotation relaxation of DNA supercoils
-
-
?
additional information
?
-
structure-activity relationship, overview
-
-
?
additional information
?
-
-
Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue factor, TF, via phosphorylation of serine/arginine-rich proteins. Selective inhibition of Cdc2-like kinases and DNA topoisomerase I elicite distinct changes in TF biosynthesis in TNF-alpha-stimulated endothelial cells, which impact endothelial procoagulant activity, overview
-
-
?
additional information
?
-
-
DNA topoisomerase IB catalyzes the relaxation of supercoiled DNA through the transient cleavage of one strand of a DNA duplex, molecular dynamics simulation of wild-type and mutant K681A enzymes, the N-terminal and C-terminal regions of the core domain show a slightly larger and a slightly smaller displacements, respectively, in the wild type than in the mutant enzyme, overview
-
-
?
additional information
?
-
-
human cells can rapidly activate and deactivate DNA topoisomerase I in response to a signal molecule, the activity of DNA topoisomerase I is highly regulated in HuT 78 cells upon treatment with interleukin-2, overview
-
-
?
additional information
?
-
-
reversible reaction. TopI produces a single strand break in DNA, allowing relaxation of DNA during its replication. The single strand break is then religated, thus restoring the DNA double strands. The enzymatic mechanism involves two sequential transesterification reactions. The cleavage reaction involves the active site Tyr723 acting as a nucleophile. A phenolic oxygen attacks a DNA phosphodiester bond, forming an intermediate in which the 3' end of the broken strand is covalently attached by an O4-phosphodiester bond to TopI tyrosine. The religation step consists of transesterification involving a nucleophilic attack by the hydroxyl oxygen at the 5' end of the broken strand. The equilibrium constant of the breakage and closure reactions is close to unity
-
-
?
additional information
?
-
-
Top1 functionally interacts with splicing factor ASF/SF2, alternative splicing factor/splicing factor 2 modulating its the function to prevent genomic instability in S phase
-
-
?
additional information
?
-
-
cleavage of oligonucleotide substrates 5'-GAAAAAAGACTTAG-3' and 5'-TAAAAATTTTTCTAAGTCTTTTTTC-3'. Crucial role for the linker domain and occurrence of a long range communication between the linker and the active site region, overview
-
-
?
additional information
?
-
-
substrate is pBR322 DNA, structure-activity relationship study, overview
-
-
?
additional information
?
-
-
substrate is pBR322 or pHC624 supercoiled DNA
-
-
?
additional information
?
-
-
substrate is supercoiled plasmid pSP73KB DNA, a multiple metallation of the short nucleotide sequences on the scissile strand, immediately downstream of the cleavage site impedes the cleavage by top1. Top1-mediated cleavage of a 30-bp oligonucleotide duplex
-
-
?
additional information
?
-
-
substrate is superhelical DNA in plasmid supercoiled pBR322, with deoxy-nucleotides, relaxation
-
-
?
additional information
?
-
-
Top1 relaxes supercoiled structures in DNA, thus creating a nick. Top1 cleaves a phosphodiester bond near the 3' end of the nick and forms a covalent bond with the 3' end of the newly formed break. This process involves the catalytic tyrosine residue necessary for nucleophilic attack and disruption of a phosphodiester bond in DNA. and it involves poly(ADP-ribose) polymerase 1, that phosphoribosylates the enzyme and affect binding to DNA, overview. Interaction of human recombinant DNA topoisomerase 1 with linear and circular DNA structures containing a nick or short gap but lacking a specific Top1 recognition site, using circular M13mp19 phage DNA and the 34mer DNA duplex containing uracil in position 16 of one of the duplex strands (U-G) as substrate. Partial inhibition of the Top1-DNAadduct formation upon addition of poly(ADP ribose) polymerase 1 in the absence of NAD+ is shown, whereas in the presence of NAD+ formation of a high molecular weight product, most likely corresponding to poly(ADP) ribosylated Top1-DNA adduct, is observed. Top1 covalent adducts with DNA containing a singlestranded break or a short gap in the absence of a recognition site are also formed with involvement of the catalytic tyrosine residue in the enzyme active center
-
-
?
additional information
?
-
-
TopI catalyzes supercoiled plasmid DNA relaxation
-
-
?
additional information
?
-
Topo I catalyses two distinct reactions, the DNA relaxation and the phosphorylation of serine/arginine motifs which are present in essential splicing factors in a mutually exclusive manner, structure-function relationship, molecular dynamics modelling, overview
-
-
?
additional information
?
-
-
Topo I catalyses two distinct reactions, the DNA relaxation and the phosphorylation of serine/arginine motifs which are present in essential splicing factors in a mutually exclusive manner, structure-function relationship, molecular dynamics modelling, overview
-
-
?
additional information
?
-
-
cleavage of supercoiled DNA by topoisomerase I
-
-
?
additional information
?
-
-
substrate for DNA topo I is pBR322 plasmid DNA
-
-
?
additional information
?
-
-
substrate for DNA topo I is supercoiled pBR322 plasmid DNA
-
-
?
additional information
?
-
-
substrate is negatively and positively supercoiled pBR322 DNA. Topoisomerase I removes positive superhelical twists about 10fold faster than it does negative superhelical twists
-
-
?
additional information
?
-
-
substrate is negatively supercoiled pBR322 plasmid DNA
-
-
?
additional information
?
-
-
usage of a 3'-end radiolabeled DNA substrate, a 117-bp DNA oligonucleotide
-
-
?
additional information
?
-
-
human topoisomerase I is a dual-activity enzyme. First, it transiently nicks double-stranded DNA. Next, topo I is a kinase that phosphorylates SR proteins, essential splicing factors, and regulators of splicing composed of one or two RNA recognition motifs (RRMs) followed by the RS domain (RS) and containing numerous serine-arginine repeats. Topo I is one of several protein kinases that phosphorylate SR proteins, enzymes of both families, SRPK1 and CLK1
-
-
?
additional information
?
-
-
the enzyme catalyzes the relaxation of supercoiled DNA during DNA replication and transcription
-
-
?
additional information
?
-
-
enzyme substrates are S(hTopI)Id16, S(PosC)Id33, and fluorescently labeled detection oligonucleotides ID16-TAMRA and ID33-6FAM
-
-
?
additional information
?
-
-
substrate is supercoiled plasmid DNA, and oligonucleotide substrate CL14 , 5'-GAAAAAAGACTTAG-3', annealed with CP25 complementary strand (5'-TAAAAATTTTTCTAAGTCTTTTTTC-3)', that is 5'-phosphorylated with unlabelled ATP
-
-
?
additional information
?
-
-
DNA binding and subunit interaction analysis of wild-type and mutant enzymes, overview
-
-
?
additional information
?
-
TopIIIbeta possesses a weak, ATP-independent relaxation activity towards negatively supercoiled DNA only
-
-
?
additional information
?
-
-
TopIIIbeta possesses a weak, ATP-independent relaxation activity towards negatively supercoiled DNA only
-
-
?
additional information
?
-
the active site tyrosine is located at the 327 position within a highly conserved GYISYPRTES sequence
-
-
?
additional information
?
-
-
the active site tyrosine is located at the 327 position within a highly conserved GYISYPRTES sequence
-
-
?
additional information
?
-
TopIIIbeta possesses a weak, ATP-independent relaxation activity towards negatively supercoiled DNA only
-
-
?
additional information
?
-
the active site tyrosine is located at the 327 position within a highly conserved GYISYPRTES sequence
-
-
?
additional information
?
-
-
the enzyme has at least two different active centers capable of processing apurinic/apyrimidinic site DNA
-
?
additional information
?
-
-
the topoisomerase and DNA repair activities reside in different parts of the protein and the DNA repair activity is dispensable for the topoisomerase catalytic activity
-
?
additional information
?
-
-
topo V contains a signature motif of leucine-responsive regulatory proteins and therefore might also act as a transcriptional regulator, in addition to being a topoisomerase and an apurinic/apyrimidinic lyase
-
?
additional information
?
-
-
enzyme controls the topological state of DNA
-
-
?
additional information
?
-
-
mapping cleavage sites on single-stranded DNA substrate Mtop with length of 216 bases amplified from topA gene of Mycobacterium tuberculosis, substrate is negatively supercoiled DNA
-
-
?
additional information
?
-
the mycobacterial topoisomerase I physically interacts with its ribokinase both in vitro and in vivo with opposite effects on their respective function, overview. Interaction analysis, overview
-
-
?
additional information
?
-
-
the mycobacterial topoisomerase I physically interacts with its ribokinase both in vitro and in vivo with opposite effects on their respective function, overview. Interaction analysis, overview
-
-
?
additional information
?
-
-
topoisomerase I shows a negative interplay between MazF protein Rv1495. Through its C-terminal domain, MtbTopA physically interacts with and inhibits the mRNA cleavage activity of Rv1495, overview. Rv1495, in turn, inhibits the DNA cleavage activity of MtbTopA as well as its function of relaxation of supercoiled DNA
-
-
?
additional information
?
-
-
structure-function analysis of MtTOP1, overview
-
-
?
additional information
?
-
substrate is supercoiled plasmid DNA
-
-
?
additional information
?
-
-
substrate is supercoiled plasmid DNA
-
-
?
additional information
?
-
enzyme activity on relaxation of supercoiled pUC18 DNA or on 5' end labeled oligonucleotides having the strong topoisomerase I site, the enzyme cleaves DNA at preferred sites in a pattern similar to its ortholog from Mycobacterium smegmatis
-
-
?
additional information
?
-
-
enzyme activity on relaxation of supercoiled pUC18 DNA or on 5' end labeled oligonucleotides having the strong topoisomerase I site, the enzyme cleaves DNA at preferred sites in a pattern similar to its ortholog from Mycobacterium smegmatis
-
-
?
additional information
?
-
Mycobacterium tuberculosis H37Ra / ATCC 25177
enzyme activity on relaxation of supercoiled pUC18 DNA or on 5' end labeled oligonucleotides having the strong topoisomerase I site, the enzyme cleaves DNA at preferred sites in a pattern similar to its ortholog from Mycobacterium smegmatis
-
-
?
additional information
?
-
the mycobacterial topoisomerase I physically interacts with its ribokinase both in vitro and in vivo with opposite effects on their respective function, overview. Interaction analysis, overview
-
-
?
additional information
?
-
substrate is supercoiled plasmid DNA
-
-
?
additional information
?
-
-
MsTopA stimulates the phosphorylating activity of Ms3759 on D-ribose, and physically interacts with its ribokinase both in vitro and in vivo with opposite effects on their respective function, overview. Interaction analysis, overview
-
-
?
additional information
?
-
-
topoisomerase I shows a negative interplay between MazF protein Rv1495. Through its C-terminal domain, MsTopA physically interacts with and inhibits the mRNA cleavage activity of Rv1495. Rv1495, in turn, inhibits the DNA cleavage activity of MsTopA as well as its function of relaxation of supercoiled DNA
-
-
?
additional information
?
-
-
substrate is supercoiled plasmid DNA
-
-
?
additional information
?
-
-
MstopoI carries out the DNA relaxation reaction in a processive fashion
-
-
?
additional information
?
-
-
DNA cleavage assay using a 32-mer oligonucleotide harboring strong topoI sites to yield a 5'-end-labeled 19-mer cleavage product. For intramolecular religation, 32-mer oligonucleotide harboring strong topoI sites is incubated with wild-type or deletants to yield a noncovalenty held 19-mer and 13-mer covalent protein-DNA adduct
-
-
?
additional information
?
-
-
enzyme controls the topological state of DNA
-
-
?
additional information
?
-
-
enzyme controls the topological state of DNA
-
-
?
additional information
?
-
-
catalyzes catenene formation, a reaction specific for type II topoisomerase
-
-
?
additional information
?
-
-
enzyme controls the topological state of DNA
-
-
?
additional information
?
-
-
topoisomerase I forms in vivo complexes with DNA substrates, the complexes are stabilized by irinotecan, which has DNA strand breaking ability, it leads to topisomerase poisoning and DNA damage, overview
-
-
?
additional information
?
-
-
wild-type enzyme and mutant enzyme N726H exhibit a distinctively processive mode of plasmid relaxation, mutant enzyme N726D exhibits a distributive mode of plasmid DNA relaxation
-
?
additional information
?
-
-
FOB1 affects DNA topoisomerase I in vivo cleavages in the enhancer region of the Saccharomyces cerevisiae ribosomal DNA locus. Binding to DNA of Fob1p itself may be the cause of the DNA topoisomerase I activity in the rDNA enhancer
-
-
?
additional information
?
-
-
H2O2 induces topoisomerase I-mediated DNA damage and cell death. H2O2 promotes the trapping of topoisomerase I on oxidative DNA lesions to form TOP1-DNA cleavage complexes that contribute to H2O2 toxicity
-
-
?
additional information
?
-
-
the enzyme recruits Sir2p to the rDNA
-
-
?
additional information
?
-
-
the enzyme recruits Sir2p to the rDNA
-
-
?
additional information
?
-
Sau-TopoI enzyme converts negatively supercoiled form I DNA to relaxed form II DNA in ATP-independent and Mg2+-dependent manners. Cleavage site mapping shows that the enzyme preferentially binds to and cleaves the sequence GGNN-/-CAT, with N and -/- representing any nucleotide and cleavage site, respectively
-
-
?
additional information
?
-
-
Sau-TopoI enzyme converts negatively supercoiled form I DNA to relaxed form II DNA in ATP-independent and Mg2+-dependent manners. Cleavage site mapping shows that the enzyme preferentially binds to and cleaves the sequence GGNN-/-CAT, with N and -/- representing any nucleotide and cleavage site, respectively
-
-
?
additional information
?
-
Sau-TopoI enzyme converts negatively supercoiled form I DNA to relaxed form II DNA in ATP-independent and Mg2+-dependent manners. Cleavage site mapping shows that the enzyme preferentially binds to and cleaves the sequence GGNN-/-CAT, with N and -/- representing any nucleotide and cleavage site, respectively
-
-
?
additional information
?
-
-
enzyme exhibits highly efficient reverse transcriptase activity in addition to their predicted functions
-
-
?
additional information
?
-
-
substrate is pUC19 plasmid DNA, and for supercoiling assay substrate pWHM3 plasmid DNA
-
-
?
additional information
?
-
-
enzyme exhibits highly efficient reverse transcriptase activity in addition to their predicted functions
-
-
?
additional information
?
-
-
catalyzes the conversion of a paranemic to aplectonemic joint
-
-
?
additional information
?
-
-
enzyme makes a single strand break and forms a covalent bond through the 3'-end of the broken strand
-
-
?
additional information
?
-
-
Arg130 forms electrostatic interactions with both nonbridging oxygen and the 5'-leaving group
-
-
?
additional information
?
-
-
remote phosphate contacts trigger assembly of the active site of DNA topoisomerase IB
-
-
?
additional information
?
-
-
the vaccinia type I DNA topoisomerase exhibits a strong site-specific ribonuclease activity when provided a DNA substrate that contains a single uridine ribonucleotide within a duplex DNA containing the sequence 5'CCCTU3'. The reaction involves two steps: attack of the active site tyrosine nucleophile followed by nucleophilic attack of the uridine 2'-hydroxyl to release the covalently tethered enzyme
-
-
?
additional information
?
-
-
when Vaccinia topoisomerase I is present with relaxed DNA in the presence of enrofloxacin (inhibitor of relaxation activity), it executes the reverse reaction, supercoiling the DNA
-
-
?
additional information
?
-
-
type I DNA topoisomerase from vaccinia virus, vTopo, forms a reversible covalent 3'-phosphotyrosyl linkage with a single strand of duplex DNA at the preferred sequence 5'-(C/T) CCTTp-/-N-1N-2N-3-3'. Site-specific DNA cleavage and ligation chemistry. Oscillation between an open and closed state of the covalently bound enzyme is likely important for regulating the number of DNA superhelical turns that are removed during the lifetime of the covalent complex with supercoiled substrates
-
-
?
additional information
?
-
-
the strictly conserved arginine residue proximal to the active site tyrosine of type IA topoisomerases is required for the relaxation of supercoiled DNA. DNA cleavage can still take place in the absence of Arg237 function if Mg2+ is present to enhance the interaction of the enzyme with the scissile phosphate, but DNA rejoining is inhibited in the absence of this conserved arginine, resulting in accumulation of the cleaved covalent intermediate and loss of relaxation activity. In addition to the divalent metal ions, the side chain of this arginine residue is required for the precise positioning of the phosphotyrosine linkage for nucleophilic attack by the 3'-OH end to result in DNA rejoining
-
-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
negatively supercoiled DNA
relaxed DNA
-
TopR1 can relax negative supercoils without ATP, while the extent of positive supercoiling catalyzed by TopR1 is dependent on the stoichiometry, the ATP concentration, the NaCl concentration and the assay temperature
-
-
?
supercoiled DNA
?
-
reverse gyrase induces unwinding of synthetic four-way junctions as well as forked DNA substrates, following a mechanism independent of both the ATPase and the strand cutting activity of the enzyme. Reverse gyrase works like an ATP-independent helix-destabilizing protein specific for branched DNA structures
-
-
?
supercoiled DNA
?
-
reverse gyrase induces unwinding of synthetic four-way junctions as well as forked DNA substrates, following a mechanism independent of both the ATPase and the strand cutting activity of the enzyme. Reverse gyrase works like an ATP-independent helix-destabilizing protein specific for branched DNA structures
-
-
?
supercoiled DNA
relaxed DNA
the enzyme relaxes the negative DNA supercoiling generated by RNA polymerase during transcription elongation
-
-
?
additional information
?
-
-
enzyme controls the topological state of DNA
-
-
?
additional information
?
-
-
role in control of DNA topology including regulation of supercoiling and maintenance of genetic stability
-
-
?
additional information
?
-
-
topoisomerase I works in concert with topoisomerase II to modulate the level of DNA supercoiling
-
-
?
additional information
?
-
when enzyme expression is interfered with by a cognate double-stranded RNA injection, pleiotropic phenotypes with abnormalities in germ cell proliferation, oogenesis and embryogenesis appeare
-
?
additional information
?
-
-
when enzyme expression is interfered with by a cognate double-stranded RNA injection, pleiotropic phenotypes with abnormalities in germ cell proliferation, oogenesis and embryogenesis appeare
-
?
additional information
?
-
Drosophila sp. (in: flies)
-
enzyme controls the topological state of DNA
-
-
?
additional information
?
-
-
enzyme controls the topological state of DNA
-
-
?
additional information
?
-
-
controls the DNA topology by cleaving and rejoining DNA strands and passing other DNA strands through the transient gaps, plays a crucial role in the regulation of the physiological function of the genome
-
-
?
additional information
?
-
-
plays a crucial role in controlling the physiological functions of DNA
-
-
?
additional information
?
-
-
plays a direct role in the regulation of transcriptional initiation by acting as a repressor of the basal-level transcription
-
-
?
additional information
?
-
-
role of topoisomerase I in DNA replication, transcription and recombination
-
-
?
additional information
?
-
-
DNA structural alterations induced by UV lesions can be sufficient stimulus to induce cross-linking of topoisomerase I to cellular DNA
-
-
?
additional information
?
-
-
Topo I is the first endogenous interaction partner for c-Jun in the regulation of cancer cell proliferation. Topo I and JNK-c Jun pathway cooperate in the regulation of eGFR gene expression and in the proliferation of HT-1080 cells
-
-
?
additional information
?
-
-
Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue factor, TF, via phosphorylation of serine/arginine-rich proteins. Selective inhibition of Cdc2-like kinases and DNA topoisomerase I elicite distinct changes in TF biosynthesis in TNF-alpha-stimulated endothelial cells, which impact endothelial procoagulant activity, overview
-
-
?
additional information
?
-
-
DNA topoisomerase IB catalyzes the relaxation of supercoiled DNA through the transient cleavage of one strand of a DNA duplex, molecular dynamics simulation of wild-type and mutant K681A enzymes, the N-terminal and C-terminal regions of the core domain show a slightly larger and a slightly smaller displacements, respectively, in the wild type than in the mutant enzyme, overview
-
-
?
additional information
?
-
-
human cells can rapidly activate and deactivate DNA topoisomerase I in response to a signal molecule, the activity of DNA topoisomerase I is highly regulated in HuT 78 cells upon treatment with interleukin-2, overview
-
-
?
additional information
?
-
-
reversible reaction. TopI produces a single strand break in DNA, allowing relaxation of DNA during its replication. The single strand break is then religated, thus restoring the DNA double strands. The enzymatic mechanism involves two sequential transesterification reactions. The cleavage reaction involves the active site Tyr723 acting as a nucleophile. A phenolic oxygen attacks a DNA phosphodiester bond, forming an intermediate in which the 3' end of the broken strand is covalently attached by an O4-phosphodiester bond to TopI tyrosine. The religation step consists of transesterification involving a nucleophilic attack by the hydroxyl oxygen at the 5' end of the broken strand. The equilibrium constant of the breakage and closure reactions is close to unity
-
-
?
additional information
?
-
-
Top1 functionally interacts with splicing factor ASF/SF2, alternative splicing factor/splicing factor 2 modulating its the function to prevent genomic instability in S phase
-
-
?
additional information
?
-
-
human topoisomerase I is a dual-activity enzyme. First, it transiently nicks double-stranded DNA. Next, topo I is a kinase that phosphorylates SR proteins, essential splicing factors, and regulators of splicing composed of one or two RNA recognition motifs (RRMs) followed by the RS domain (RS) and containing numerous serine-arginine repeats. Topo I is one of several protein kinases that phosphorylate SR proteins, enzymes of both families, SRPK1 and CLK1
-
-
?
additional information
?
-
-
the enzyme catalyzes the relaxation of supercoiled DNA during DNA replication and transcription
-
-
?
additional information
?
-
TopIIIbeta possesses a weak, ATP-independent relaxation activity towards negatively supercoiled DNA only
-
-
?
additional information
?
-
-
TopIIIbeta possesses a weak, ATP-independent relaxation activity towards negatively supercoiled DNA only
-
-
?
additional information
?
-
TopIIIbeta possesses a weak, ATP-independent relaxation activity towards negatively supercoiled DNA only
-
-
?
additional information
?
-
-
the topoisomerase and DNA repair activities reside in different parts of the protein and the DNA repair activity is dispensable for the topoisomerase catalytic activity
-
?
additional information
?
-
-
topo V contains a signature motif of leucine-responsive regulatory proteins and therefore might also act as a transcriptional regulator, in addition to being a topoisomerase and an apurinic/apyrimidinic lyase
-
?
additional information
?
-
-
enzyme controls the topological state of DNA
-
-
?
additional information
?
-
the mycobacterial topoisomerase I physically interacts with its ribokinase both in vitro and in vivo with opposite effects on their respective function, overview. Interaction analysis, overview
-
-
?
additional information
?
-
-
the mycobacterial topoisomerase I physically interacts with its ribokinase both in vitro and in vivo with opposite effects on their respective function, overview. Interaction analysis, overview
-
-
?
additional information
?
-
-
topoisomerase I shows a negative interplay between MazF protein Rv1495. Through its C-terminal domain, MtbTopA physically interacts with and inhibits the mRNA cleavage activity of Rv1495, overview. Rv1495, in turn, inhibits the DNA cleavage activity of MtbTopA as well as its function of relaxation of supercoiled DNA
-
-
?
additional information
?
-
the mycobacterial topoisomerase I physically interacts with its ribokinase both in vitro and in vivo with opposite effects on their respective function, overview. Interaction analysis, overview
-
-
?
additional information
?
-
-
MsTopA stimulates the phosphorylating activity of Ms3759 on D-ribose, and physically interacts with its ribokinase both in vitro and in vivo with opposite effects on their respective function, overview. Interaction analysis, overview
-
-
?
additional information
?
-
-
topoisomerase I shows a negative interplay between MazF protein Rv1495. Through its C-terminal domain, MsTopA physically interacts with and inhibits the mRNA cleavage activity of Rv1495. Rv1495, in turn, inhibits the DNA cleavage activity of MsTopA as well as its function of relaxation of supercoiled DNA
-
-
?
additional information
?
-
-
MstopoI carries out the DNA relaxation reaction in a processive fashion
-
-
?
additional information
?
-
-
enzyme controls the topological state of DNA
-
-
?
additional information
?
-
-
enzyme controls the topological state of DNA
-
-
?
additional information
?
-
-
enzyme controls the topological state of DNA
-
-
?
additional information
?
-
-
topoisomerase I forms in vivo complexes with DNA substrates, the complexes are stabilized by irinotecan, which has DNA strand breaking ability, it leads to topisomerase poisoning and DNA damage, overview
-
-
?
additional information
?
-
-
FOB1 affects DNA topoisomerase I in vivo cleavages in the enhancer region of the Saccharomyces cerevisiae ribosomal DNA locus. Binding to DNA of Fob1p itself may be the cause of the DNA topoisomerase I activity in the rDNA enhancer
-
-
?
additional information
?
-
-
H2O2 induces topoisomerase I-mediated DNA damage and cell death. H2O2 promotes the trapping of topoisomerase I on oxidative DNA lesions to form TOP1-DNA cleavage complexes that contribute to H2O2 toxicity
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additional information
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type I DNA topoisomerase from vaccinia virus, vTopo, forms a reversible covalent 3'-phosphotyrosyl linkage with a single strand of duplex DNA at the preferred sequence 5'-(C/T) CCTTp-/-N-1N-2N-3-3'. Site-specific DNA cleavage and ligation chemistry. Oscillation between an open and closed state of the covalently bound enzyme is likely important for regulating the number of DNA superhelical turns that are removed during the lifetime of the covalent complex with supercoiled substrates
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Co2+
K+
KCl
-
maximal activity of wild-type enzyme at 150 mM, maximal activity of mutant enzyme N726D at 75-100 mM
Mg2+
Mn2+
Na+
NaCl
Zn2+
additional information
Ca2+
-
CaCl2 slightly increases activity of enzyme forms MW 100000 and MW 110000 in presence of 150 mM NaCl. Activates enzyme form MW 150000 to the same extent as MgCl2
Ca2+
-
optimal concentration is 4-8 mM, can replace the effect of Mg2+
Ca2+
-
divalent cation is not required. 7-10 mM Ca2+ stimulates 10fold to 20fold
K+
-
stimulates, optimal concentration: 175-200 mM. K+ stimulates 10-15% more effectively than Na+
Mg2+
-
no requirement for a divalent cation, stimulation in presence of 10 mM MgCl2
Mg2+
-
no absolute requirement for divalent cation. 10 mM Mg2+ stimulates 5fold to 10fold
Mg2+
-
no requirement for divalent cation but 10fold to 20fold stimulation by the presence of MgCl2
Mg2+
-
wild-type EcTOP1 does not require Mg2+ for DNA cleavage, but R321 mutants do
Mg2+
-
enzyme forms MW 100000 and MW 110000: addition of both 5 mM Mg2+ and 5 mM NaCl markedly increases activity. Little activity in presence of 2.5-7.5 mM MgCl2 alone. Enzyme form MW 150000: only MgCl2 is required for full activity, maximal activation at 5 mM
Mg2+
-
dependent on, low concentrations of MgCl2 are sufficient to obtain efficient catalysis
Mg2+
-
required for DNA substrate relaxation, optimal at 5-12.5 mM
Mg2+
-
the DNA cleavage activity of MtTOP1-G116 S is Mg2+-dependent
Mg2+
required, acidic residues D111 and E115 are involved in Mg2+ coordination
Mg2+
-
divalent cation is not required. 7-10 mM Mg2+ stimulates 10fold to 20fold
Mg2+
dependent on, most favorable divalent cation for the relaxation activity of the enzyme
Mg2+
-
wild-type YpTOP1 does not require Mg2+ for DNA cleavage, but R327 mutants do
Mn2+
-
slightly increases activity of enzyme forms MW 100000 and MW 110000 in presence of 150 mM NaCl
Mn2+
-
optimal concentration is 2-8 mM, can replace the effect of Mg2+
Na+
-
optimal activity at 150-200 mM Na+ or other monovalent cations. Below a concentration of 100 mM Na+, the enzyme acts in a processive fashion, and above 150 mM in a nonprocessive fashion
Na+
-
enzyme forms MW 100000 and MW 110000: addition of both 5 mM Mg2+ and 5 mM NaCl markedly increases activity, optimal NaCl concentration is 150-200 mM, inhibition above 300 mM
Na+
-
no activity in absence of NaCl or at NaCl concentrations greater than 0.3 M, maximal activity at 0.15 M NaCl
Na+
-
monovalent cation required, in presence of EDTA optimal activity between 100 and 250 mM NaCl
NaCl
-
when the NaCl concentration increases from 10 mM to 200 mM, positive supercoiling activity of TopR1 decreases. At 300 mM NaCl, TopR1 is no longer able to positively supercoil DNA, but it only relaxes negatively supercoiled DNA. Higher NaCl concentrations clearly inhibits the DNA relaxation catalyzed by TopR1 (400 mM). The increase of the DNA linking number catalyzed by TopR1 is inhibited with increasing salt concentration
Zn2+
-
required. The zinc-bound YrdD has a strong binding affinity for single-stranded DNA and protects ssDNA from the DNase I digestion in vitro. Zinc-bound YrdD can protect ssDNA from the DNase I digestion
Zn2+
-
TopA is an iron and zinc binding protein, it contains a C-terminal zinc-binding region that is required for relaxation of the negatively supercoiled DNA. Whereas the zinc-bound TopA is fully active to relax the negatively supercoiled DNA, the iron-bound TopA has little or no enzyme activity
additional information
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topoisomerase I is able to bind both iron and zinc in the C-terminal region in vivo, unlike the zinc-bound topoisomerase I, the iron-bound enzyme fails to relax the negatively supercoiled DNA. YrdD, the homologue of the topoisomerase I C-terminal region, can also bind both iron and zinc in vivo
additional information
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synthesis of 2,4-diaryl chromenopyridines and evaluation of their topoisomerase I inhibitory activity, cytotoxicity, and structure-activity relationship, overview. 2-Furyl or 2-thienyl at 2- or 4-position of central pyridine is crucial in displaying topo I or II inhibitory activity and cytotoxicity
additional information
the enzyme shows no relaxation activity on supercoiled DNA in the absence of divalent cations, no or poor stimulation by Ca2+ and Mn2+
additional information
-
the enzyme shows no relaxation activity on supercoiled DNA in the absence of divalent cations, no or poor stimulation by Ca2+ and Mn2+
additional information
zinc binding is not required for DNA relaxation activity
additional information
-
zinc binding is not required for DNA relaxation activity
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(-)-epigallocatechin
i.e. (2R,3R)-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-1-benzopyran-3,5,7-triol
(-)-gallocatechin
i.e. (2R,3R)-3,5,7-trihydroxy-2-(3,4,5-trihydroxyphenyl)-2,3-dihydro-4H-1-benzopyran-4-one
(1,1',1'',1'''-[(1,4-dihydroporphyrin-5,10,15,20-tetrayl-k4N21,N22,N23,N24)tetrakis(benzene-4,1-diylmethanediyl)]tetrakis[1-methylpiperidiniumato(2-)])nickel(4+) tetraiodide
-
-
(1,1',1'',1'''-[(1,4-dihydroporphyrin-5,10,15,20-tetrayl-k4N21,N22,N23,N24)tetrakis(benzene-4,1-diylmethanediyl)]tetrakis[1-methylpiperidiniumato(2-)])zinc(4+) tetraiodide
-
-
(1-phenyl-ethylideneamino)-acetic acid
-
0.05 mM, 53% vTopo RNase activity remaining, 10% cTopo relaxation activity remaining
(1S,12aR,12bR)-1,4,9,12a-tetrahydroxy-1,2,11,12,12a,12b-hexahydroperylene-3,10-dione
i.e. altertoxin I
(1S,12S,12aR,12bR)-1,4,9,12,12a-pentahydroxy-1,2,11,12,12a,12b-hexahydroperylene-3,10-dione
i.e. 6-epi-stemphytriol
(2,2',2'',2''',2'''',2''''',2'''''',2'''''''-[(5,28-dihydro-29H,31H-tetrabenzoporphine-2,3,9,10,16,17,23,24-octayl-k4N29,N30,N31,N32)octasulfanediyl]octakis(N,N-diethyl-N-methylethanaminiumato)(2-))zinc(8+) octaiodide
-
-
(2-hydroxy-naphthalen-1-yl)-acetic acid
-
0.05 mM, 48% vTopo RNase activity remaining
(2E)-3-[(6R,7S)-7-[(2,4-dihydroxy-6-methylbenzoyl)oxy]-6-hydroxy-7-methyl-8-oxo-6,7,8,8a-tetrahydro-1H-2-benzopyran-3-yl]prop-2-enoic acid
i.e. pinophilin F
(2E)-3-[(7R)-7-[(2,4-dihydroxy-6-methylbenzoyl)oxy]-7-methyl-6,8-dioxo-6,7,8,8a-tetrahydro-1H-2-benzopyran-3-yl]prop-2-enoic acid
i.e. (-)-mitorubrinic acid
(2R)-2-[(2S,3S)-3-acetamido-5-oxooxolan-2-yl]-2-hydroxy-N-[(S)-[(3S)-8-hydroxy-1-oxo-3,4-dihydro-1H-2-benzopyran-3-yl][(propan-2-yl)amino]methyl]acetamide (non-preferred name)
i.e. AI-77-C
(2S,3R)-5-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-3-(hydroxymethyl)-8-phenyl-2,3,8,9-tetrahydro-10H-[1,4]dioxino[2,3-f]chromen-10-one
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(2S,3R,4S,6R)-4-amino-2-methyl-6-((3-(2-phenyl-1-tosyl-1H-indol-3-yl)prop-2-yn-1-yl)oxy)tetrahydro-2H-pyran-3-ol
-
92.8% inhibition at 0.1 mM
(2S,3R,4S,6R)-4-amino-2-methyl-6-((3-(2-phenylbenzofuran-3-yl)prop-2-yn-1-yl)oxy)tetrahydro-2H-pyran-3-ol
-
25.5% inhibition at 0.1 mM
(2S,3R,4S,6R)-4-amino-2-methyl-6-((3-(2-phenylbenzo[b]thiophen-3-yl)prop-2-yn-1-yl)oxy)tetrahydro-2H-pyran-3-ol
-
32.2% inhibition at 0.1 mM
(2S,3R,4S,6R)-4-amino-2-methyl-6-(3-(2-phenyl-1H-indol-3-yl)prop-2-ynyloxy)tetrahydro-2H-pyran-3-ol
-
20.2% inhibition at 0.1 mM; 8.2% inhibition at 0.1 mM
(2S,3S,6R)-2-methyl-6-(3-(2-phenyl-1-tosyl-1H-indol-3-yl)prop-2-ynyloxy)tetrahydro-2H-pyran-3-amine
-
43.2% inhibition at 0.1 mM
(2S,3S,6R)-2-methyl-6-(3-(2-phenyl-1H-indol-3-yl)prop-2-ynyloxy)tetrahydro-2H-pyran-3-amine
-
4.0% inhibition at 0.1 mM
(2S,3S,6R)-2-methyl-6-(3-(2-phenylbenzo[b]thiophen-3-yl)prop-2-ynyloxy)tetrahydro-2H-pyran-3-amine
-
7.9% inhibition at 0.1 mM
(3-hydroxy-4-thiocyanato-benzylsulfanyl)-acetic acid
-
0.05 mM, 45% vTopo RNase activity remaining
(3beta,5alpha,6beta,17alpha,22E)-6-methoxyergost-22-ene-3,5-diol
i.e. 3beta,5alpha-dihydroxy-6beta-methoxy-ergosta-7,22-diene
(3beta,5alpha,6beta,17alpha,22E)-ergost-22-ene-3,5,6-triol
i.e. ergosta-7,22-diene-3beta,5alpha,6beta-triol
(3S,8aR)-3-[[(3S)-7,7-dimethyl-3-(2-methylbut-3-en-2-yl)-2-oxo-1,2,3,7-tetrahydropyrano[2,3-g]indol-3-yl]methyl]-8a-methoxyhexahydropyrrolo[1,2-a]pyrazine-1,4-dione
i.e. notoamide Q
(5aR,7R,9aR)-7',7',8,8-tetramethyl-1',2,3,7',8a,9-hexahydro-1H,2'H,5H,6H,8H,10H-spiro[5a,9a-(epiminomethano)cyclopenta[f]indolizine-7,3'-pyrano[2,3-g]indole]-2',5,10-trione
i.e. (-)-versicolamide B
(5aS,13bS)-1,5a,9,13-tetrahydroxy-3,7-dimethyl-5,5a-dihydro-4H,10H,12H,14H,16H-pyrano[3''',4''',5''':4'',5'']naphtho[2'',1'':4',5']furo[2',3':7,8]naphtho[1,8-cd]pyran-4,10,16-trione (non-preferred name)
i.e. bacillosporin C
(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]-isoquinolin-3-yl)carbamic acid
-
-
(6bR,7aS,12aS,14aS)-6b-hydroxy-3,3-dimethyl-14a-(2-methylbut-3-en-2-yl)-3,6b,7,7a,10,11,12,12a,14a,15-decahydro-8H,13H-pyrano[2,3-g]pyrrolo[1'',2'':4',5']pyrazino[1',2':1,5]pyrrolo[2,3-b]indole-8,13-dione
i.e. notoamide D
(7aR,12aS)-5-methylidene-12-[(4-methylphenyl)sulfonyl]-7,7a,12,12a-tetrahydrobenzo[6,7]chromeno[4,3-b]indol-13(5H)-one
(7aS,12aS)-10-methoxy-5-methylidene-5,7,7a,12a-tetrahydro-13H-[1]benzofuro[3,2-c]benzo[g]chromen-13-one
(7aS,12aS)-11-methoxy-5-methylidene-13-oxo-5,7a,12a,13-tetrahydro-7H-[1]benzofuro[3,2-c]benzo[g]chromene-9-carbaldehyde
(7aS,12aS)-5-methylidene-5,7,7a,12a-tetrahydro-13H-[1]benzofuro[3,2-c]benzo[g]chromen-13-one
(7aS,12aS,13aR)-3,3,14,14-tetramethyl-3,7,11,12,13,13a,14,15-octahydro-8H,10H-7a,12a-(epiminomethano)indolizino[6,7-h]pyrano[3,2-a]carbazole-8,16-dione
i.e. 6-epi-stephacidin A
(7aS,12aS,13aS)-3,3,14,14-tetramethyl-3,7,11,12,13,13a,14,15-octahydro-8H,10H-7a,12a-(epiminomethano)indolizino[6,7-h]pyrano[3,2-a]carbazole-8,16-dione
i.e. stephacidin A
(7R)-3-[(1E)-3-hydroxyprop-1-en-1-yl]-7-methyl-6,8-dioxo-6,7,8,8a-tetrahydro-1H-2-benzopyran-7-yl 2,4-dihydroxy-6-methylbenzoate
i.e. (-)-mitorubrinol
(7S,8S,8aS)-7-hydroxy-3-[(1E)-3-hydroxyprop-1-en-1-yl]-7-methyl-6-oxo-6,7,8,8a-tetrahydro-1H-2-benzopyran-8-yl 2,4-dihydroxy-6-methylbenzoate
i.e. pinophilin B
(7S,8S,8aS)-8-hydroxy-3-[(1E)-3-hydroxyprop-1-en-1-yl]-7-methyl-6-oxo-6,7,8,8a-tetrahydro-1H-2-benzopyran-7-yl 2,4-dihydroxy-6-methylbenzoate
i.e. pinophilin D
(9-([2-(1H-Indol-3-yl)ethyl]amino)-3-acridinyl)(4-methyl-1-piperazinyl)methanone
-
-
(9-([2-(1H-indol-3-yl)ethyl]amino)acridin-3-yl)(4-methylpiperazin-1-yl)methanone
-
-
(9-([2-(1H-indol-3-yl)ethyl]amino)acridin-4-yl)(4-methylpiperazin-1-yl)methanone
-
-
(9-[(1-benzylpiperidin-4-yl)amino]acridin-3-yl)(4-methylpiperazin-1-yl)methanone
-
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(S)-6-(6-nitrobenzothiazol-2-yl)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine
-
-
(S)-6-(benzothiazol-2-yl)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-7H-pyrido[1,2,3-de][1,4]-benzoxazine
-
-
1,1',1'',1'''-[1,4-dihydroporphyrin-5,10,15,20-tetrayltetrakis(benzene-4,1-diylmethanediyl)]tetrakis(1-methylpiperidinium) tetraiodide
-
-
1,1',1'',1'''-[1,4-dihydroporphyrin-5,10,15,20-tetrayltetrakis(benzene-4,1-diylmethanediyl)]tetrakis[3-(ethoxycarbonyl)-1-methylpiperidinium] tetraiodide
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-
1,1',1'',1'''-[1,4-dihydroporphyrin-5,10,15,20-tetrayltetrakis(benzene-4,1-diylmethanediyl)]tetrakis[3-(hydroxymethyl)-1-methylpiperidinium] tetraiodide
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-
1,2'-binaphthalene-7',8-dicarboxylic acid
-
does not inhibit supercoil relaxation at 10 microM concentration. IC90 (compound concentration at which 90% or higher inhibition is observed) 2 microM, using high-throughput screen, relaxation inhibition 0%
1,3-bis(4-amino-2-methylquinolin-6-yl)urea
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 2 microM, using high-throughput screen, relaxation inhibition 40%
1,3-[6-(3-Amino-1-propyl)-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline]-[5',6'-dihydro-6'-(3'-amino-1'-propyl)-5',11'-dioxo-11'H-indeno[1,2-c]-isoquinoline]propane bis(trifluoroacetate)
-
1,5-dideoxy-1-(5,11-dioxo-5,11-dihydro-6H-indeno[1,2-c]isoquinolin-6-yl)-D-xylo-hexitol
-
-
1-(3,4-dihydroxybenzyl)isoquinoline-6,7-diol
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 10 microM, using high-throughput screen, relaxation inhibition 80%
1-(alpha-L-idopyranosyl)-N-(2-methylbenzoyl)-5-(methylsulfanyl)-1H-1,2,4-triazol-3-amine
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1-(hydroxymethyl)-3-(2-hydroxypropan-2-yl)-2-(5-methoxy-9H-beta-carbolin-1-yl)-cyclopentanol
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1-deoxy-1-(3-nitro-5,11-dioxo-5,11-dihydro-6H-indeno[1,2-c]isoquinolin-6-yl)-D-glucitol
-
-
1-deoxy-1-(5,11-dioxo-5,11-dihydro-6H-indeno[1,2-c]isoquinolin-6-yl)-D-allitol
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-
1-deoxy-1-(5,11-dioxo-5,11-dihydro-6H-indeno[1,2-c]isoquinolin-6-yl)-D-arabinitol
-
-
1-deoxy-1-(5,11-dioxo-5,11-dihydro-6H-indeno[1,2-c]isoquinolin-6-yl)-D-galactitol
-
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1-deoxy-1-(5,11-dioxo-5,11-dihydro-6H-indeno[1,2-c]isoquinolin-6-yl)-D-glucitol
-
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1-deoxy-1-(5,11-dioxo-5,11-dihydro-6H-indeno[1,2-c]isoquinolin-6-yl)-D-mannitol
-
-
1-deoxy-1-(5,11-dioxo-5,11-dihydro-6H-indeno[1,2-c]isoquinolin-6-yl)-D-ribitol
-
-
1-ethoxycarbonyl-naphthoquinone-[2,3-d]indolizidine-6,11-dione
-
0.1 mg/ml, 4.1% inhibition of relaxation
1-ethyl-3-(5-aminobenzimidazol-2-yl)-6-fluoro-7-(4-methyl-1-piperazinyl)-4(1H)-quinolone
-
-
1-ethyl-3-(6-aminobenzoimidazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-1,8-naph- thyridin-4(1H)-one
-
-
1-ethyl-3-(6-aminobenzoimidazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-1,8-naphthyridin-4(1H)-one
-
-
1-ethyl-3-(6-aminobenzoimidazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-4(1H)-quinolone
-
-
1-ethyl-3-(6-chlorobenzimidazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-1,8-naphthyridine-4(1H)-one
-
-
1-ethyl-3-(6-chlorobenzimidazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-4(1H)-quinolone
-
-
1-ethyl-3-(6-nitrobenzimidazol-2-yl)-6-fluoro-7-(4-methyl-1-piperazinyl)-4(1H)-quinolone
-
-
1-ethyl-3-(6-nitrobenzimidazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-1,8-naphthyridine-4(1H)-one
-
-
1-ethyl-3-(6-nitrobenzimidazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-4(1H)-quinolone
-
-
1-ethyl-3-(6-nitrobenzothiazol-2-yl)-6,8-difluoro-7-(3-methylpiperazin-1-yl)-4(1H)-quinolone
-
-
1-ethyl-3-(6-nitrobenzothiazol-2-yl)-6-fluoro-7-(4-methylpiperazin-1-yl)-4(1H)-quinolone
-
-
1-ethyl-3-(6-nitrobenzothiazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-1,8-naphthyridine-4(1H)-one
-
-
1-ethyl-3-(6-nitrobenzothiazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-4(1H)-quinolone
-
-
1-ethyl-3-(6-nitrobenzoxazol-2-yl)-6,8-difluoro-7-(3-methylpiperazin-1-yl)-4(1H)-quinolone
-
interacts with DNA-Top I complex and induces cancer cell apoptosis to produce antitumor effects, in vivo inhibition of anchorage-dependent colony formation
1-ethyl-3-(6-nitrobenzoxazol-2-yl)-6-fluoro-7-(4-methylpiperazin-1-yl)-4(1H)-quinolone
-
-
1-ethyl-3-(6-nitrobenzoxazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-1,8-naphthyridine-4(1H)-one
-
-
1-ethyl-3-(benzimidazol-2-yl)-6,8-difluoro-7-(3-methylpiperazin-1-yl)-4(1H)-quinolone
-
9% and 11% inhibition at 0.1 mM and 0.02 mM, respectively
1-ethyl-3-(benzothiazol-2-yl)-6,8-difluoro-7-(3-methylpiperazin-1-yl)-4(1H)-quinolone
-
-
1-ethyl-3-(benzothiazol-2-yl)-6-fluoro-7-(4-methylpiperazin-1-yl)-4(1H)-quinolone
-
-
1-ethyl-3-(benzothiazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-1,8-naphthyridine-4(1H)-one
-
-
1-ethyl-6,8-difluoro-7-(3-methylpiperazin-1-yl)-3-(6-nitro-1,3-benzoxazol-2-yl)quinolin-4(1H)-one
-
interacts with DNA-Top I complex and induces cancer cell apoptosis to produce antitumor effects
1-ethylKuQuinone
-
synthesis of the pentacyclic-diquinoid synthetic compound, overview. It efficiently inhibits the cleavage step of the enzyme reaction fitting well into the catalytic site. When incubated with the binary topoisomerase-DNA cleaved complex, the compound helps the enzyme to remove itself from the cleaved DNA and close the DNA gap, increasing the religation rate. Et-KuQ inhibits the relaxation activity of Top1. The compound also induces the religation of the stalled enzyme-camptothecin-DNA ternary complex. Docking and molecular modeling, overview
1-hydroxy-3-[2-hydroxy-3-[(2-hydroxyethyl)amino]propoxy]-9H-xanthen-9-one
-
1.1% inhibition at 0.02 mM
1-hydroxy-3-[2-hydroxy-3-[(3-hydroxypropyl)amino]propoxy]-9H-xanthen-9-one
-
3.5% inhibition at 0.02 mM
1-methyl-3-(2-hydroxypropan-2-yl)-2-(5-methoxy-9H-beta-carbolin-1-yl)-cyclopentanol
-
-
1-[2-(dimethylamino)ethyl]-3-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]quinoxalin-2-amine
-
-
1-[3-[(dicyclohexylamino)methyl]-2,4-dihydroxyphenyl]ethanone
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 100 microM, using high-throughput screen, relaxation inhibition 50%
10-methoxy-9-{2-[(2,9,10-trimethoxy-5,6-dihydroisoquino[3,2-a]isoquinolinium-3-yl)oxy]ethoxy}[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolin-7-ium dichloride
-
synthetic protoberberine alkaloid, highly active
10-methoxy-9-{3-[(2,9,10-trimethoxy-5,6-dihydroisoquino[3,2-a]isoquinolinium-3-yl)oxy]propoxy}[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolin-7-ium dichloride
-
synthetic protoberberine alkaloid, highly active
10-methoxy-9-{4-[(2,9,10-trimethoxy-5,6-dihydroisoquino[3,2-a]isoquinolinium-3-yl)oxy]butoxy}[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolin-7-ium dichloride
-
synthetic protoberberine alkaloid, highly active
11-hydroxy-3-[(1R)-1-hydroxy-3-methylbutyl]-4-methoxy-9-methyl-5H,7H-dibenzo[b,g][1,5]dioxocin-5-one
i.e. vermixocin A
11-[2-(dimethylamino)ethoxy]-2-methyl-4H-naphtho[2,3-h]chromene-4,7,12-trione
-
-
14-(10'-aminodecyl-1'-aminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride
-
14-(11'-aminoundecyl-1'-aminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride
-
14-(12'-aminododecyl-1'-aminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride
-
14-(2'-aminoethyl-1'-aminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride
-
14-(3'-aminopropyl-1'-aminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride
-
14-(3-aminopropyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one dihydrochloride
-
14-(3-N-ethanolaminopropyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trifluoroacetate
-
14-(4'-aminobutyl-1'-aminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride
-
14-(5'-aminopentyl-1'-aminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride
-
14-(6'-aminohexyl-1'-aminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride
-
14-(7'-aminoheptyl-1'-aminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride
-
14-(8'-aminooctyl-1'-aminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride
-
14-(9'-aminononyl-1'-aminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride
-
14-aminomethyl-12H-5,11a-diazadibenzo[b,h]fluoren-11-one dihydrochloride
-
14-[(1-imidazolyl)propylaminomethyl]-12H-5,11a-diazadibenzo[b,h]fluoren-11-one
-
14-[1-(N-methylpiperazinylmethyl)]-2H-5,11a-diazadibenzo[b,h]fluoren-11-one
-
14-[3(1-morpholinopropyl)]-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trifluoroacetate
-
14-[3-(1-imidazolylpropyl)]-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trifluoroacetate
-
14-[3-(N,N-dimethylaminopropyl)]-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trifluoroacetate
-
14-[N-(S)-3-hydroxypyrrolidinomethyl]-12H-5,11a diazadibenzo[b,h]fluoren-11-one
-
17-beta-3-oxo-18-norandrost-4-ene-17-carboxylic acid -4-bromo-benzene sulfonic acid ester
-
partial or complete inhibition of hTopo is only observed at relatively high compound concentrations in the range 5 to 20 microM
17-beta-3-oxo-18-Norandrost-4-ene-17-carboxylic acid-4-bromo-benzene sulfonic acid ester
-
shows significant inhibition of plasmid supercoil relaxation even at 100 nM concentrations. IC90 (compound concentration at which 90% or higher inhibition is observed) 0.5 microM, using high-throughput screen, relaxation inhibition 50%
2'-(4-(3,6,9,12,15,18-hexaoxahenicos-20-ynyloxy)phenyl)-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzo[d]imidazole
2'-(4-ethoxyphenyl)-5-(4-methylpiperazinyl)-2,5'-bi-1H-benzimidazole
-
reversibly traps enzyme cleavage complexes with a different and more specific sequence selectivity
2'-(4-ethoxyphenyl)-6-(4-methylpiperazin-1-yl)-1H,3'H,2,5'-bisbenzimidazole
-
Hoechst 33342
2'-(4-hydroxyphenyl)-5-(4-methylpiperazinyl)-2,5'-bi-1H-benzimidazole
-
reversibly traps enzyme cleavage complexes with a different and more specific sequence selectivity
2'-[4-([6-[(but-3-yn-1-yl)oxy]hexyl]oxy)phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
2'-[4-[(heptadec-16-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
2(2.6-dihydrobenzoyl)-3-hydroxy-5-hydroxymethylbenzoic acid methyl ester
-
2,2'-bis(8-formyl-1,6,7-trihydroxy-5-isopropyl-3-methylnaphthalene)
-
i.e. gossypol, belongs to the class II compounds which interfere with the catalytic function of topoisomerases without generating strand breaks
2,3-dimethoxy-8,9-methylenedioxy-10-(1H-imidazol-yl)methyl-11H-indeno[1,2-c]isoquinoline
-
2,3-dimethoxy-8,9-methylenedioxy-10-(4-methylpiperazin-1-yl)-methyl-11H-indeno[1,2-c]isoquinoline
-
2,3-dimethoxy-8,9-methylenedioxy-10-(4-morpholino)methyl-11H-indeno[1,2-c]isoquinoline
-
2,3-dimethoxy-8,9-methylenedioxy-10-(dimethylamino)methyl-11H-indeno[1,2-c]isoquinoline
influence of protonation state on Top1 inhibition
2,3-dimethoxy-8,9-methylenedioxy-10-(N,N',N'-trimethylethylenediamino)methyl-11H-indeno[1,2-c]isoquinoline
-
2,3-dimethoxy-8,9-methylenedioxy-10-(pyrrolidin-1-yl)methyl-11H-indeno[1,2-c]isoquinoline
influence of protonation state on Top1 inhibition
2,3-dimethoxy-8,9-methylenedioxy-10-methyl-11H-indeno[1,2-c]-isoquinoline
-
2-((6-(3-((tert-butoxycarbonyl)amino)propyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino)acetic acid
-
-
2-((6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino)acetic acid hydrochloride
-
-
2-(4-((1-(2-azidoethyl)-1H-1,2,3-triazol-4-yl)methoxy)-phenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazole
2-(4-(2-(4-(4-ethynylphenyl)-1H-1,2,3-triazol-1-yl)ethoxy)-phenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazole
2-(4-chlorophenyl)-4-(furan-3-yl)-6-(3-methylthiophen-2-yl) pyridine
-
86% inhibition at 0.1 mM
2-(4-chlorophenyl)-6-(5-chlorothiophen-2-yl)-4-(furan-2-yl) pyridine
-
53% inhibition at 0.1 mM
2-(4-[[1-(6-azidohexyl)-1H-1,2,3-triazol-4-yl]methoxy]phenyl)-6-(4-methylpiperazin-1-yl)-1H-benzimidazole
2-(5-chlorothiophen-2-yl)-4-(furan-3-yl)-6-(5-methylfuran-2-yl) pyridine
-
13.2% inhibition at 0.1 mM
2-(5-chlorothiophen-2-yl)-4-(furan-3-yl)-6-o-tolylpyridine
-
4.6% inhibition at 0.1 mM
2-(5-chlorothiophen-2-yl)-6-(furan-2-yl)-4-(furan-3-yl)pyridine
-
9.6% inhibition at 0.1 mM
2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)-N-[2-methyl-1-(morpholin-4-ylcarbonyl)propyl]acetamide
-
-
2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)-N-[3-methyl-1-[(4-methylpiperazin-1-yl)carbonyl]butyl]acetamide
-
-
2-(furan-2-carbonyl)-3-(pyridin-2-ylamino)-acrylonitrile
-
0.05 mM, 28% vTopo RNase activity remaining; 0.05 mM, 7% vTopo RNase activity remaining, 2% cTopo relaxation activity remaining
2-(furan-2-yl)-4-(furan-3-yl)-6-(3-methylthiophen-2-yl)pyridine
-
5.4% inhibition at 0.1 mM
2-(furan-2-yl)-4-(pyridin-2-yl)-5H-chromeno[4,3-b]pyridine
-
11.5% inhibition at 0.1 mM
2-(furan-2-yl)-4-(pyridin-3-yl)-5H-chromeno[4,3-b]pyridine
-
41.6% inhibition at 0.1 mM
2-(piperidin-1-yl)ethyl5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxylate
-
-
2-(pyridin-2-yl)-4-(pyridin-3-yl)-5H-chromeno[4,3-b]pyridine
-
2.6% inhibition at 0.1 mM
2-(pyridin-2-yl)-4-(thiophen-2-yl)-5H-chromeno[4,3-b]pyridine
-
48.2% inhibition at 0.1 mM
2-(pyridin-2-yl)ethyl5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxylate
-
-
2-(pyrrolidin-1-yl)ethyl 5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxylate
-
-
2-Amino-1-(1-benzyl-piperidin-4-yl)-4,9-dioxo-3a,4,9,9a-tetrahydro-1H-benzo[f]indole-3-carboxylic acid ethyl ester
-
0.1 mg/ml, 4.1% inhibition of relaxation
2-Amino-1-(2-bromo-ethyl)-4,9-dioxo-3a,4,9,9a-tetrahydro-1H-benzo[f]indole-3-carboxylic acid ethyl ester
-
0.1 mg/ml, 58.7% inhibition of relaxation
2-Amino-1-(2-hydroxy-ethyl)-4,9-dioxo-3a,4,9,9a-tetrahydro-1H-benzo[f]indole-3-carboxylic acid ethyl ester
-
0.1 mg/ml, 27.3% inhibition of relaxation
2-Amino-1-(4-amino-phenyl)-4,9-dioxo-3a,4,9,9a-tetrahydro-1H-benzo[f]indole-3-carboxylic acid ethyl ester
-
0.1 mg/ml, 9.4% inhibition of relaxation
2-Amino-1-(4-fluoro-phenyl)-4,9-dioxo-3a,4,9,9a-tetrahydro-1H-benzo[f]indole-3-carboxylic acid ethyl ester
-
0.1 mg/ml, 67.8% inhibition of relaxation
2-Amino-1-benzyl-4,9-dioxo-3a,4,9,9a-tetrahydro-1H-benzo[f]indole-3-carboxylic acid ethyl ester
-
0.1 mg/ml, 15.7% inhibition of relaxation
2-Amino-1-cyclohexyl-4,9-dioxo-3a,4,9,9a-tetrahydro-1H-benzo[f]indole-3-carboxylic acid ethyl ester
-
0.1 mg/ml, 12.2% inhibition of relaxation
2-Amino-1-isopropyl-4,9-dioxo-3a,4,9,9a-tetrahydro-1H-benzo[f]indole-3-carboxylic acid ethyl ester
-
0.1 mg/ml, 8.6% inhibition of relaxation
2-amino-3-ethoxycarbonyl-N-(4-fluorophenyl)benz[f]indole-4,9-dione
-
potent inhibitor
2-amino-3-ethoxycarbonyl-N-methyl-benz[f]indole-4,9-dione
-
0.1 mg/ml, 5.6% inhibition of relaxation
2-Amino-4,9-dioxo-1-p-tolyl-3a,4,9,9a-tetrahydro-1H-benzo[f]indole-3-carboxylic acid ethyl ester
-
0.1 mg/ml, 4.3% inhibition of relaxation
2-Amino-4,9-dioxo-1-phenyl-3a,4,9,9a-tetrahydro-1H-benzo[f]indole-3-carboxylic acid ethyl ester
-
0.1 mg/ml, 2.9% inhibition of relaxation
2-bromoethyl 5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxylate
-
-
2-hydroxy-3-ethoxycarbonyl-N-(3,4-dimethylphenyl)-benz[f]indole-4,9-dione
-
0.1 mg/ml, 6.6% inhibition of relaxation
2-methylidenebutanedioic acid
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 10 microM, using high-throughput screen, relaxation inhibition 100%
2-phenyl-4-(thiophen-3-yl)-5H-chromeno[4,3-b]pyridine
-
3.6% inhibition at 0.1 mM
2-pyridyl-1H-anthra[1,2-d]imidazole-6,11-dione
-
The hypochromicity observed on DNA addition is too low for determination of binding constants
2-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino]-2-oxoacetic acid
-
-
2-[(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]-isoquinolin-3-yl)amino]acetic acid
-
-
2-[4-[(4,11-dihydroxy-5,10-dioxo-5,10-dihydro-1H-naphtho[2,3-f]indol-3-yl)methyl]piperazin-1-yl]ethyl acetate
-
-
2-[[2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3,4-dihydro-2H-chromen-3-yl]oxy]-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromene-3,4,5,7-tetrol
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 0.5 microM, using high-throughput screen, relaxation inhibition 70%; IC90 (compound concentration at which 90% or higher inhibition is observed) 1 microM, using high-throughput screen, relaxation inhibition 100%
20-thio camptothecin
-
analogue of camptothecin, inhibit a modified human topoisomerase I
3,3'-diindolylmethane
-
(DIM) novel DNA topoisomerase I poison, which is a class I noncompetitive inhibitor, strongly inhibits Leishmania donovani topoisomerase I and stabilizes topoisomerase I-DNA cleavable complex
3,3'-[butane-1,4-diylbis(oxy)]bis(2,9,10-trimethoxy-5,6-dihydroisoquino[3,2-a]isoquinolinium) dichloride
-
synthetic protoberberine alkaloid, highly active
3,3'-[ethane-1,2-diylbis(oxy)]bis(2,9,10-trimethoxy-5,6-dihydroisoquino[3,2-a]isoquinolinium) dichloride
-
synthetic protoberberine alkaloid, highly active. Strongly stabilize the enzyme-DNA binary complex at low concentration (50100microM). From 0.1 to 1 mM, their ability to stabilize is weak
3,3'-[propane-1,3-diylbis(oxy)]bis(2,9,10-trimethoxy-5,6-dihydroisoquino[3,2-a]isoquinolinium) dichloride
-
synthetic protoberberine alkaloid, highly active
3,5-bis-dimethylaminomethyl-benzene-1,2-diol
-
0.05 mM, 52% vTopo RNase activity remaining, 30% cTopo relaxation activity remaining
3-(1,3-benzoxazol-2-yl)-1-ethyl-6-fluoro-7-(4-methylpiperazin-1-yl)quinolin-4(1H)-one
-
-
3-(1,3-benzoxazol-2-yl)-1-ethyl-6-fluoro-7-(piperazin-1-yl)-1,8-naphthyridin-4(1H)-one
-
-
3-(1H-benzimidazol-2-yl)-1-ethyl-6,8-difluoro-7-(3-methylpiperazin-1-yl)quinolin-4(1H)-one
-
-
3-(1H-benzimidazol-2-yl)-1-ethyl-6-fluoro-7-(4-methylpiperazin-1-yl)quinolin-4(1H)-one
-
-
3-(1H-benzimidazol-2-yl)-1-ethyl-6-fluoro-7-(piperazin-1-yl)-1,8-naphthyridin-4(1H)-one
-
-
3-(1H-benzimidazol-2-yl)-1-ethyl-6-fluoro-7-(piperazin-1-yl)quinolin-4(1H)-one
-
-
3-(2,3-dimethoxy-5,12-dioxo-5,12-dihydro-6H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinolin-6-yl)propan-1-aminium chloride
-
higher activity than the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
3-(2-phenyl-1-benzofuran-3-yl)prop-2-yn-1-yl 3-amino-2,3,6-trideoxy-b-D-arabino-hexopyranoside
-
77.8% inhibition at 0.1 mM
3-(2-phenyl-1-benzothiophen-3-yl)prop-2-yn-1-yl 3-amino-2,3,6-trideoxy-b-D-arabino-hexopyranoside
-
36.9% inhibition at 0.1 mM
3-(2-phenyl-1H-indol-3-yl)prop-2-yn-1-yl 3-amino-2,3,6-trideoxy-b-D-arabino-hexopyranoside
-
8.8% inhibition at 0.1 mM
3-(4-chlorophenyl)-1-(4'-hydroxyphenyl)-2-propen-1-one
-
chalcones (1,3-diaryl-2-propen-1-ones) are alpha, beta-unsaturated ketones with cytotoxic and anticancer properties. Compound has the highest Hammett and log P values (0.23 and 4.21, respectively) and exerted both highest cytotoxicity and strongest DNA topoisomerase I inhibition
3-(4-methylphenyl)-1-(4'-hydroxyphenyl)-2-propen-1-one
-
chalcones (1,3-diaryl-2-propen-1-ones) are alpha, beta-unsaturated ketones with cytotoxic and anticancer properties. Compound shows moderate interference with the DNA topoisomerase I
3-(5-phenyl-1H-pyrrol-2-yl)-propanoic acid
-
0.05 mM, 35% vTopo RNase activity remaining
3-(imidazolyl-1-propyl)-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline hydrochloride
-
higher activity than the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
3-(piperidin-1-yl)propyl-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxylate
-
-
3-(pyrrolidin-1-yl)propyl-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxylate
-
-
3-amino-6-(3-aminopropyl)-5,6-dihydro-9-methoxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline dihydrochloride
-
-
3-amino-6-(3-azidopropyl)-5,6-dihydro-9-methoxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
-
-
3-benzo[1,3]dioxol-5-yl-1,1,1-trihydroxy-2-oxopropanoic acid
-
0.05 mM, 9% vTopo RNase activity remaining, 8% cTopo relaxation activity remaining
3-benzo[1,3]dioxol-5-yl-2-oxopropionic acid
-
potent inhibitor of the enzyme from vaccinia virus, does not inhibit the human enzyme
3-bromopropyl 5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxylate
-
-
3-cyano-5,11-dihydro-6-[3-(1H-imidazolyl)propyl]-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinoline
-
-
3-cyano-5,11-dihydro-6-[3-(dimethylamino)propyl]-5,11-dioxoindeno[1,2-c]isquinoline
-
-
3-cyano-6,11-dihydro-5,11-dioxo-6-(3-morpholinylpropyl)-5H-indeno[1,2-c]isoquinoline
-
-
3-cyano-6,11-dihydro-5,11-dioxo-6-[3-(dimethylamino)propyl]-5H-indeno[1,2-c]isoquinoline
-
-
3-iodo-9-methoxy-6-[3-(dimethylamino)propyl]-5H-indeno-[1,2-c]isoquinoline-5,11(6H)-dione
-
-
3-morpholinopropyl-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxylate
-
-
3-O-[N-(1-naphthyl)-carbamoyl]-17-beta-[N-(1-naphthyl)-carbamoyl]-oleanolic acid
-
-
3-O-[N-(phenylsulfonyl)-carbamoyl-17beta-N-(phenylsulfonyl)amide]-oleanolic acid
-
-
3-phenyl-1-(4'-hydroxyphenyl)-2-propen-1-one
-
chalcones (1,3-diaryl-2-propen-1-ones) are alpha, beta-unsaturated ketones with cytotoxic and anticancer properties. Compound shows moderate interference with the DNA topoisomerase I
3-pyridyl-1H-anthra[1,2-d]imidazole-6,11-dione
-
The hypochromicity observed on DNA addition is too low for determination of binding constants
3-thiiranylmethyloxy-1-hydroxy-5-azaxanthone
-
50% and 27% inhibition at 0.1 mM and 0.02 mM, respectively
3-[(1-azabicyclo[2.2.2]oct-3-ylamino)methyl]-4,11-dihydroxy-1H-naphtho[2,3-f]indole-5,10-dione
-
-
3-[(1-hydroxyethyl-piperazine)-1-propyl]-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
-
similar activity as the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
3-[(1-methylpiperazinyl)-1-propyl]-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
-
weak activity
3-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-3-oxopropanoic acid hydrochloride
-
-
3-[(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]-isoquinolin-3-yl)amino]-3-oxopropanoic acid
-
-
3-[(morpholinyl)-1-propyl]-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
-
higher activity than the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
3-[(thiomorpholinyl)-1-propyl]-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
-
similar activity as the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
3-[1-[(4-methylphenyl)sulfonyl]-2-phenyl-1H-indol-3-yl]prop-2-yn-1-yl 3-amino-2,3,6-trideoxy-b-D-arabino-hexopyranoside
-
80.1% inhibition at 0.1 mM
3-[4-(1-ethyl-2-methyl-propenyl)-phenoxy]-benzoic acid
-
0.05 mM, 33% vTopo RNase activity remaining
4,11-bis([2-[(2-hydroxyethyl)amino]ethyl]amino)-1H-naphtho[2,3-f]indole-5,10-dione
-
-
4,11-dihydroxy-3-[(4-methylpiperazin-1-yl)methyl]-1H-naphtho[2,3-f]indole-5,10-dione
-
-
4,4',4'',4'''-ethane-1,1,2,2-tetrayltetrakis(2,6-dichlorophenol)
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 10 microM, using high-throughput screen, relaxation inhibition 60%
4,4',4'',4'''-[1,4-dihydroporphyrin-5,10,15,20-tetrayltetrakis(benzene-4,1-diylmethanediyl)]tetrakis(4-methylmorpholin-4-ium) tetraiodide
-
-
4,4'-dimethyl-biphenyl-2,5,2',5'-tetraol
-
0.05 mM, 30% vTopo RNase activity remaining
4,4-bis(3,5-dibromo-4-hydroxyphenyl)pentanoic acid
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 1 microM, using high-throughput screen, relaxation inhibition 100%
4-(1-methylaminomethylsulfanyl-ethyl)-benzene-1,2-diol
-
0.05 mM, 27% vTopo RNase activity remaining
4-(2-hydroxyethyl)-6-([2-[(2-hydroxyethyl)amino]ethyl]amino)-1,2,3,4-tetrahydronaphtho[2,3-f]quinoxaline-7,12-dione
-
-
4-(5-chlorofuran-2-yl)-2-(3-chlorophenyl)-6-(3-methylthiophen-2-yl) pyridine
-
5.9% inhibition at 0.1 mM
4-(5-chlorofuran-2-yl)-2-(3-chlorophenyl)-6-(5-chlorothiophen-2-yl) pyridine
-
13% inhibition at 0.1 mM
4-(5-chlorofuran-2-yl)-2-(4-chlorophenyl)-6-(3-methylthiophen-2-yl) pyridine
-
5.1% inhibition at 0.1 mM
4-(5-chlorofuran-2-yl)-2-(5-chlorothiophen-2-yl)-6-(furan-2-yl) pyridine
-
23% inhibition at 0.1 mM
4-(5-chlorofuran-2-yl)-2-(5-chlorothiophen-2-yl)-6-p-tolylpyridine
-
14% inhibition at 0.1 mM
4-(5-chlorofuran-2-yl)-2-(furan-2-yl)-6-(3-methylthiophen-2-yl) pyridine
-
7.8% inhibition at 0.1 mM
4-(5-chlorofuran-2-yl)-6-(3-methylthiophen-2-yl)-2,3'-bipyridine
-
21% inhibition at 0.1 mM
4-(furan-2-yl)-2-(pyridin-2-yl)-5H-chromeno[4,3-b]pyridine
-
4.4% inhibition at 0.1 mM
4-(furan-2-yl)-2-(thiophen-2-yl)-5H-chromeno [4,3-b]pyridine
-
9.2% inhibition at 0.1 mM
4-(furan-3-yl)-6-(thiophene-2-yl)-[2,4']-bipyridyl
-
shows moderate topoisomerase I inhibitory activities when compared to camptothecin
4-(furan-3-yl)-6-(thiophene-3-yl)-[2,4']-bipyridyl
-
shows moderate topoisomerase I inhibitory activities when compared to camptothecin
4-(pyridin-2-yl)-2-(thiophen-3-yl)-5H-chromeno[4,3-b]pyridine
-
3.3% inhibition at 0.1 mM
4-(thiophene-3-yl)-6-(thiophene-2-yl)-[2,2']-bipyridyl
-
shows significant topoisomerase I inhibitory activities at 20 microM and 100 microM concentration
4-(thiophene-3-yl)-6-(thiophene-2-yl)-[2,4']-bipyridyl
-
shows significant topoisomerase I inhibitory activities at 20 microM and 100 microM concentration
4-chloro-N-[5-imino-1-(quinoxalin-2-yl)-2,5-dihydro-1H-1,2,4-triazol-3-yl]-5-methyl-2-sulfanylbenzenesulfonamide
-
-
4-phenyl-2-(pyridin-2-yl)-5H-chromeno[4,3-b]pyridine
-
3.1% inhibition at 0.1 mM
4-phenyl-2-(thiophen-2-yl)-5H-chromeno[4,3-b]pyridine
-
5.5% inhibition at 0.1 mM
4-[(2-carboxyphenyl)carbonyl]benzene-1,2-dicarboxylic acid
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 1 microM, using high-throughput screen, relaxation inhibition 100%
4-[(3-(1-imidazolyl))propyloxy]phenyl-1H-anthra[1,2-d]imidazole-6,11-dione
-
shows strong DNA binding
4-[(3-(1-tetrazolyl))propoxy]phenyl-1H-anthra[1,2-d]imidazole-6,11-dione
-
shows weak DNA binding
4-[(3-(4-(2-hydroxyethyl)-1-piperazinyl))propyloxy]phenyl-1H-anthra[1,2-d]imidazole-6,11-dione
-
shows strong DNA binding
4-[(3-(4-methyl-1-piperazinyl))propyloxy]phenyl-1H-anthra-[1,2-d]imidazole-6,11-dione
-
shows strong DNA binding
4-[(3-(4-morpholinyl))propyloxy]phenyl-1H-anthra[1,2-d]imidazole-6,11-dione
-
shows weak DNA binding
4-[(3-diethylamino)propyloxy]phenyl-1H-anthra[1,2-d]imidazole-6,11-dione
-
shows strong DNA binding
4-[(3-dimethylamino)propyloxy]phenyl-1H-anthra[1,2-d]imidazole-6,11-dione
-
shows strong DNA binding
4-[(6-(3-((tert-butoxycarbonyl)amino)propyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino]-4-oxobutanoic acid
-
-
4-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-4-oxobutanoic acid hydrochloride
-
-
4-[(6-chloro-2-methoxyacridin-9-yl)amino]-2-[(4-methylpiperazin-1-yl)methyl]phenol
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 100 microM, using high-throughput screen, relaxation inhibition 100%
4-[3-[ethyl(methyl)amino]propyl]furo[3,2-c]phenanthridine-5,10,11(4H)-trione
-
4-[5-(4-methyl-1-piperazinyl)-1H,1H'-2,5'-bibenzimidazol-2'-yl]phenol
-
Hoechst 33258
4-[[(2-fluorophenyl)carbamoyl]amino]benzenesulfonamide
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 100 microM, using high-throughput screen, relaxation inhibition 40%
4-[[(6-amino-3-methylpyrido[2,3-b]pyrazin-8-yl)amino]methyl]benzenesulfonamide
-
-
4-[[2-(6-amino-8-oxo-1,2,3,4,5,8-hexahydropyrido[2,3-b]pyrazin-2-yl)ethyl]amino]benzoic acid
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 100 microM, using high-throughput screen, relaxation inhibition 100%
5,12-dioxo-N-(2-(piperidin-1-yl)ethyl)-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
5,12-dioxo-N-(3-(piperidin-1-yl)propyl)-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
5,12-dioxo-N-(3-(pyrrolidin-1-yl)propyl)-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
5,12-dioxo-N-(3-phenylpropyl)-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
5,5'-(1,1'-dihydroxy-8,8'-dimethoxy-6,6'-dimethyl-2,2'-binaphthalene-4,4'-diyl)bis(1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline-6,8-diol)
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 10 microM, using high-throughput screen, relaxation inhibition 40%
5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl D-allopyranoside
-
dideschlororebeccamycin, RM762, indolocarbazole derivative
5-(2,2-dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyl-6-[(4-methylphenyl)sulfonyl]tetrahydrofuro[2,3-d][1,3]dioxole
-
shows significant inhibition of plasmid supercoil relaxation even at 100 nM concentrations. IC90 (compound concentration at which 90% or higher inhibition is observed) 1 microM, using high-throughput screen, relaxation inhibition 50%
5-deoxy-5-(5,11-dioxo-5,11-dihydro-6H-indeno[1,2-c]isoquinolin-6-yl)-D-arabinitol
-
-
5-[(6-(3-((tert-butoxycarbonyl)amino)propyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino]-5-oxopentanoic acid
-
-
5-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-5-oxopentanoic acid hydrochloride
-
-
5-[[3-(dimethylamino)propyl]amino]-3-methylpyrimido[4,5-b]quinoline-2,4(3H,4aH)-dione
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 5 microM, using high-throughput screen, relaxation inhibition 70%
6'-(thiophene-2-yl)-[3,4',2',4'']-terpyridine
-
shows moderate topoisomerase I inhibitory activities when compared to camptothecin
6'-(thiophene-2-yl)-[4,2',4',4'']-terpyridine
-
shows moderate topoisomerase I inhibitory activities when compared to camptothecin
6-(3-(1H-imidazol-1-yl)propyl)-8-methoxy-3-nitro-5Hindeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(3-aminopropyl)-3-(methylamino)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(3-aminopropyl)-5,6-dihydro-8-methoxy-3-nitro-5,11-dioxo-11H-indeno[1,2-c]isoquinoline hydrochloride
-
-
6-(3-aminopropyl)-5,6-dihydro-9-methoxy-3-iodo-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
-
-
6-(3-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
class of non-camptothecin topoisomerase I inhibitors, exert cytotoxicity by trapping the covalent complex formed between DNA and Top1during relaxation of DNA supercoils
6-(3-aminopropyl)-7-methoxy-3-nitro-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(3-aminopropyl)-9-methoxy-3-nitro-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(3-azidopropyl)-5,6-dihydro-8-methoxy-3-nitro-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
-
-
6-(3-bromopropyl)-5,6-dihydro-8-methoxy-3-nitro-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
-
-
6-(3-homopiperazinyl-1-propyl)-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline dihydrochloride
-
higher activity than the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
6-(3-piperazinyl-1-propyl)-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline dihydrochloride
-
similar activity as the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
6-(3-thiazolylamino-1-propyl)-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline dihydrochloride
-
higher activity than the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
6-(4-methylpiperazin-1-yl)-2'-(4-(10-(prop-2-ynyloxy)-decyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
6-(4-methylpiperazin-1-yl)-2'-(4-(12-(prop-2-ynyloxy)-dodecyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
6-(4-methylpiperazin-1-yl)-2'-(4-(6-(prop-2-ynyloxy)-hexyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
6-(4-methylpiperazin-1-yl)-2'-(4-(8-(prop-2-ynyloxy)-octyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
6-(4-methylpiperazin-1-yl)-2-(4-(2-(4-(oct-7-ynyl)-1H-1,2,3-triazol-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazole
6-(furan-2-yl)-4-(furan-3-yl)-[2,2']-bipyridyl
-
shows moderate topoisomerase I inhibitory activities when compared to camptothecin
6-(furan-2-yl)-4-(furan-3-yl)-[2,4']-bipyridyl
-
shows moderate topoisomerase I inhibitory activities when compared to camptothecin
6-(furan-2-yl)-4-(thiophene-2-yl)-[2,4']-bipyridyl
-
shows significant topoisomerase I inhibitory activities at 20 microM and 100 microM concentration
6-(furan-2-yl)-4-(thiophene-3-yl)-[2,4']-bipyridyl
-
shows moderate topoisomerase I inhibitory activities when compared to camptothecin
6-(furan-2-yl)-[3,4',2',4'']-terpyridine
-
shows significant topoisomerase I inhibitory activities at 20 microM and 100 microM concentration
6-N-(1-hydroxymethyl-2-hydroxy)ethylamino-12,13-dihydro-2,10-dihydroxy-13-(beta-D-glucopyranosyl)-5H-indolo[2,3-a]-pyrrolo[3,4-c]-carbazole-5,6(6H)-dione
-
also effective against cancer cells with P-glycoprotein-mediated resistance to adriamycin or taxol
6-N-formylamino-12,13-dihydro-1,11-dihydroxy-13-(beta-D-glucopyranosyl)-5G-indolo(2,3-a)pyrrolo(3,4-c)carbarole-5,7(6H)-dione
-
more potent than camptothecin for inhibiting the top1-mediated religation step
6-[(2S)-2,3-dihydroxypropyl]-2,3-dimethoxy-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-[(3-morpholylethylamino)-1-propyl]-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
-
higher activity than the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
6-[(6-(3-((tert-butoxycarbonyl)amino)propyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino]-6-oxohexanoic acid
-
-
6-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-6-oxohexanoic acid hydrochloride
-
-
6-[3-(1H-imidazol-1-yl)propyl]-2,3-dimethoxy-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
higher activity than the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
6-[3-(1H-imidazol-1-yl)propyl]-2,3-dimethoxy-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
-
-
6-[3-(1H-imidazol-1-yl)propyl]-3-nitro-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione hydrochloride
-
higher activity than the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
6-[3-(1H-imidazol-1-yl)propyl]-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
higher activity than the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
6-[3-(3-hydroxypiperidinyl)-1-propyl]-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline hydrochloride
-
higher activity than the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
6-[3-(4-aminopiperidinyl)-1-propyl]-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline dihydrochloride
-
weak activity
6-[3-pyrazolyl-1-propyl]-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
-
similar activity as the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
6-[3-[(2-hydroxyethyl)amino]propyl]-2,3-dimethoxy-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
-
-
6-[3-[2-(1,2,4)]-triazolyl-1-propyl]-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline hydrochloride
-
higher activity than the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
6-{3-[(2-hydroxyethyl)amino]propyl}-2,3-dimethoxy-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
i.e. MJ-III-65
7,8-dimethoxy-2-pyridin-4-yl-4H-chromen-4-one
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 10 microM, using high-throughput screen, relaxation inhibition 100%
8,9-dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-one
8,9-dimethoxy-5-(2-N-methylaminoethyl)-2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-one
8-bromo-9-cyano-7-(alpha-L-xylofuranosyl)-3,7-dihydroimidazo[1,2-c]pyrrolo[3,2-e]pyrimidin-4-ium
-
-
8-methoxy-6-(3-morpholinopropyl)-3-nitro-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
9,9'-[butane-1,4-diylbis(oxy)]bis(10-methoxy-5,6-dihydro[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolin-7-ium) dichloride
-
synthetic protoberberine alkaloid, highly active
9,9'-[ethane-1,2-diylbis(oxy)]bis(10-methoxy-5,6-dihydro[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolin-7-ium)dichloride
-
synthetic protoberberine alkaloid, highly active
9,9'-[heptane-1,7-diylbis(oxy)]bis(10-methoxy-5,6-dihydro[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolin-7-ium) dichloride
-
synthetic protoberberine alkaloid, highly active
9,9'-[hexane-1,6-diylbis(oxy)]bis(10-methoxy-5,6-dihydro[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolin-7-ium) dichloride
-
synthetic protoberberine alkaloid, highly active
9,9'-[pentane-1,5-diylbis(oxy)]bis(10-methoxy-5,6-dihydro[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolin-7-ium) dichloride
-
synthetic protoberberine alkaloid, highly active
9,9'-[propane-1,3-diylbis(oxy)]bis(10-methoxy-5,6-dihydro[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolin-7-ium) dichloride
-
synthetic protoberberine alkaloid, highly active. Strongly stabilize the enzyme-DNA binary complex at low concentration (50100microM). From 0.1 to 1 mM, their ability to stabilize is weak
9-O-[2-(4-methylpiperazin-1-yl)ethyl]berberine
-
synthetic protoberberine alkaloid
baicalein
-
(5,6,7-trihydroxyflavone), naturally occurring flavone, isolated from the stem-bark of Oroxylum indicum, binds to the free enzyme and also intercalates into the DNA at a very high concentration (300 mM) without binding to the minor grove
biphenyl-3,4'-diylbis(arsonic acid)
-
shows significant inhibition of plasmid supercoil relaxation even at 100 nM concentrations. IC90 (compound concentration at which 90% or higher inhibition is observed) 0.1 microM, using high-throughput screen, relaxation inhibition 50%
bis(2,2-dichloro-6-[[2-(hydroxy-kO)benzylidene]amino-kN]-4H-1,3,2-benzodioxastannin-4-onato)copper(2+)
-
-
bis-1,2-[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-(ethylamino)-ethylamino]ethane tetra(trifluoroacetate)
-
bis-1,2-[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-ethylamino]ethane bis(trifluoroacetate)
weak activity
bis-1,2-[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-propylamino]ethane bis(trifluoroacetate)
similar activity as 1 microM camptothecin
bis-1,3-[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-ethylamino]propane bis(trifluoroacetate)
similar activity as 1 microM camptothecin
bis-1,3-[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-propylamino]propane bis(trifluoroacetate)
similar activity as 1 microM camptothecin
bis-1,3-[(5,6-dihydro-5,11-diketo-2,3-dimethoxy-11H-indeno-[1,2-c]isoquinoline)-6-ethylamino]propane bis(trifluoroacetate)
-
bis-1,3-[(5,6-dihydro-5,11-diketo-2,3-dimethoxy-11H-indeno-[1,2-c]isoquinoline)-6-propylamino]propane bis(trifluoroacetate)
-
bis-1,3-[(5,6-dihydro-5,11-diketo-3-nitro-11H-indeno[1,2-c]isoquinoline)-6-ethylamino]propane bis(trifluoroacetate)
-
bis-1,4-[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-(6-propyl-tert-BOCamino)]butane
weak activity
bis-1,4-[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-propylamino]butane bis(trifluoroacetate)
similar activity as 6-(3-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
bis[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-(ethylamino)-ethyl]amine tris(trifluoroacetate)
similar activity as 6-(3-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
bis[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-ethyl]amine
weak activity
bis[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-propyl]amine
weak activity
bis[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-propyl]methylamine
weak activity
bis[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)]-(6-ethyl,6'-propyl)ammonium Trifluoroacetate
weak activity
bis[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)]-(6-propyl,6'-butyl)amine hydrochloride
weak activity
chrysin 6-C-beta-D-glucopyranosyl 8-C-alpha-L-arabinopyranoside
-
flavonoid from Scutellaria amoena
cis-2',5,7-trihydroxyflavanonol 3-O-beta-D-glucopyranoside
-
flavonoid from Scutellaria amoena
colcemid
-
microtubule inhibitor, arrests cells in M phase, followed by induction of apotosis, 1 and 5 ng/ml colcemid display only modest cytotoxic effects. 10, 50 and 100 ng/ml induce pronounced cell death as measured by flow cytometry analysis
diaqua(2,2'-diamino-4,4'-bi-1,3-thiazole)oxosulfato-vanadium(IV) tetrahydrate
-
-
-
dibiphenyl-4-yl(hydroxy)acetic acid
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 1 microM, using high-throughput screen, relaxation inhibition 100%
dihydroquercetin
i.e. (2R,3R)-2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-2,3-dihydro-4H-1-benzopyran-4-one
dihydroxy[4-[(2-hydroxyethyl)sulfamoyl]phenyl]oxoantimonate(2-)
-
does not inhibit supercoil relaxation at 10 microM concentration. IC90 (compound concentration at which 90% or higher inhibition is observed) 5 microM, using high-throughput screen, relaxation inhibition 0%
enrofloxacin
-
inhibits DNA relaxation.When Vaccinia topoisomerase I is present with relaxed DNA in the presence of enrofloxacin, it executes the reverse reaction, supercoiling the DNA
erybraedin C
-
binds irreversibly to the enzyme alone, probably in proximity of the active site, without abolishing enzyme binding to the DNA
ethyl 10-amino-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
-
-
ethyl 10-bromo-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
-
-
ethyl 10-chloro-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
-
-
ethyl 10-fluoro-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
-
-
ethyl 10-hydroxy-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
-
-
ethyl 10-methyl-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
-
-
ethyl 2-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5Hindeno[1,2-c]isoquinolin-3-yl)amino]acetate hydrochloride
-
-
ethyl 2-[(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino]acetate
-
-
ethyl 6,11-dioxo-6,11-dihydrobenzo[f]-pyrido[1,2-alpha]indole 12-carboxylate
-
-
ethyl 7-amino-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
-
-
ethyl 7-bromo-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
-
-
ethyl 7-chloro-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
-
-
ethyl 7-fluoro-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
-
-
ethyl 7-hydroxy-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
-
-
ethyl 7-methyl-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
-
-
evodiamine
-
EVO, an alkaloidal compound isolated from Evodia rutaecarpa, is able to inhibit supercoiled plasmid DNA relaxation catalyzed by TopI by stabilizing topoisomerase I-DNA cleavable complex
gamma-aminobutyric acid
-
GABA, regulates the activity of topo I in mouse cerebellum sections, slightly and transiently inhibits topo I activity
glutamate
-
regulates the activity of topo I in mouse cerebellum sections. Exhibits a significant time-dependent inhibition of topo I activity but no effect of the enzyme protein level
intoplicine
-
molecular interactions with DNA and topoisomerases and in ternary complexes, binding modes and biological effects of intoplicine derivatives
isodiospyrin
-
inhibits by direct binding to htopo I, inhibits relexation activity and kinase activity, antagonizes camptothecin-induced DNA cleavage by htopo I
methyl (2R)-2-([3-[(3,3-dimethyloxiran-2-yl)methyl]-4-hydroxyphenyl]methyl)-4-hydroxy-3-(4-hydroxyphenyl)-5-oxo-2,5-dihydrofuran-2-carboxylate
i.e. butyrolactone I
methyl (2R)-4-hydroxy-2-[[4-hydroxy-3-(3-methylbutyl)phenyl]methyl]-3-(4-hydroxyphenyl)-5-oxo-2,5-dihydrofuran-2-carboxylate
i.e. butyrolactone III
methyl (7aS,12aS)-5-methylidene-13-oxo-5,7a,12a,13-tetrahydro-7H-[1]benzofuro[3,2-c]benzo[g]chromene-9-carboxylate
methyl 2-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5Hindeno[1,2-c]isoquinolin-3-yl)amino]-2-oxoacetate
-
-
methyl 2-[(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-2-oxoacetate
-
-
methyl 3-[(6-(3-((tert-butoxycarbonyl)amino)propyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino]-3-oxopropanoate
-
-
methyl 3-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5Hindeno[1,2-c]isoquinolin-3-yl)amino]-3-oxopropanoate
-
-
methyl 3-[(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-3-oxopropanoate
-
-
methyl 4-[(6-(3-((tert-butoxycarbonyl)amino)propyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino]-4-oxobutanoate
-
-
methyl 4-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5Hindeno[1,2-c]isoquinolin-3-yl)amino]-4-oxobutanoate
-
-
methyl 4-[(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-4-oxobutanoate
-
-
methyl 5-[(6-(3-((tert-butoxycarbonyl)amino)propyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino]-5-oxopentanoate
-
-
methyl 5-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5Hindeno[1,2-c]isoquinolin-3-yl)amino]-5-oxopentanoate
-
-
methyl 5-[(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-5-oxopentanoate
-
-
methyl 6-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5Hindeno[1,2-c]isoquinolin-3-yl)amino]-6-oxohexanoate
-
-
methyl 6-[(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-6-oxohexanoate
-
-
methyl N-[(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetyl]glycinate
-
-
methyl [[5-carbamoyl-6-(methylsulfanyl)-4-oxo-3-phenyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl]sulfanyl]acetate
-
-
monodentate [PtCl(diethylenetriamine)]Cl
-
presence of DNA adducts of bifunctional antitumor cisplatin or monodentate [PtCl(dien)]Cl in the substrate DNA inhibits eukaryotic top1 action, the adducts of cisplatin being more effective. Inhibition is markedly enhanced by camptothecin. Sequence preference of Pt-DNA adducts in the 161-bp substrate DNA fragment. Inhibition mechanism and interaction analysis, overview
Ms4585
-
inhibits the function of MsTopA in relaxing supercoiled DNA. The ribokinase, encoded by gene Ms4585, acts as a netaive regulator of TopA activity
-
N,N',N'',N'''-[1,4-dihydroporphyrin-5,10,15,20-tetrayltetrakis(benzene-4,1-diylmethanediyl)]tetrakis(2-hydroxy-N,N-dimethylethanaminium) tetrabromide
-
-
N,N',N'',N'''-[1,4-dihydroporphyrin-5,10,15,20-tetrayltetrakis(benzene-4,1-diylmethanediyl)]tetrakis(N,N-dimethylanilinium) tetrabromide
-
-
N,N',N'',N'''-[1,4-dihydroporphyrin-5,10,15,20-tetrayltetrakis(benzene-4,1-diylmethanediyl)]tetrakis(N-ethyl-N-methylethanaminium) tetrabromide
-
-
N,N',N'',N'''-[1,4-dihydroporphyrin-5,10,15,20-tetrayltetrakis(benzene-4,1-diylmethanediyl)]tetrakis[2-hydroxy-N-(2-hydroxyethyl)-N-methylethanaminium] tetrabromide
-
-
N,N,N-trimethyl-1H-pyridazino[4,3-b][1,4]benzothiazin-3-aminium
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 100 microM, using high-throughput screen, relaxation inhibition 50%
N,N-dimethyl(6-methyl-10,11-dioxo-10,11-dihydrophenanthro[1,2-b]furan-1-yl)methanaminium (2E)-3-carboxyprop-2-enoate
-
-
N-(2-(1H-imidazol-1-yl)ethyl)-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
N-(2-(4-methylpiperazin-1-yl)ethyl)-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
N-(2-(dimethylamino)ethyl)-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
N-(2-(pyrrolidin-1-yl)ethyl)-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
N-(2-morpholinoethyl)-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
N-(3-(4-methylpiperazin-1-yl)propyl)-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
N-(3-(diethylamino)propyl)-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
N-(3-(dimethylamino)propyl)-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
N-(3-morpholinopropyl)-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
N-[1-benzyl-2-(4-ethylpiperazin-1-yl)-2-oxoethyl]-2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetamide
-
-
N-[1-[(4-ethylpiperazin-1-yl)carbonyl]-3-methylbutyl]-2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetamide
-
-
N-[2-(Dimethylamino)ethyl]carboxamide derivatives of fused tetracyclic quinolines and quinoxalines
-
N-[6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl]acetamide
-
-
N-[6-(3-azidopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl]acetamide
-
-
N-[6-(3-hydroxypropyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl]acetamide
-
-
NH4Cl
-
can partially replace for NaCl in activation of enzyme forms MW 100000 and MW 110000
nick-containing oligonucleotides
-
inhibit DNA substrate relaxation. Synthesis of and enzyme inhibition by a series of oligonucleotides with various lengths that contain nick and topoisomerase I-binding sites, sequences, overview. The position of the nick as well as the length of the oligonucleotides are crucial factors for the inhibition of the nuclear enzyme
-
nick-containing oligonucleotides s
-
inhibit DNA substrate relaxation. Synthesis of and enzyme inhibition by a series of oligonucleotides with various lengths that contain nick and topoisomerase I-binding sites, sequences, overview. The position of the nick as well as the length of the oligonucleotides are crucial factors for the inhibition of the nuclear enzyme
-
phenazine-2,7-diylbis(arsonic acid)
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 100 microM, using high-throughput screen, relaxation inhibition 50%
pyrazoloacridine
-
completely suppresses the ability of topoisomerase I to relax supercoiled DNA at a concentration of 0.008 mM, inhibits the enzyme without trapping cleavable complexes
pyridoxal 5'-phosphate
competitive inhibitor of Candida guilliermondii topoisomerase I
R-3
-
a synthetic derivative of rebeccamycin that contains a methoxyglucose moiety appended to the indolocarbazole chromophore
R-4
-
the aglycone of a synthetic derivative of rebeccamycin that contains a methoxyglucose moiety appended to the indolocarbazole chromophore
Rv2436
inhibits the TopA activity on supercoiled DNA. The ribokinase, encoded by gene Rv2436, acts as a netaive regulator of TopA activity
-
S-Dimethylaminomethyl-N-(3,3,3-trichloro-1-hydroxy-prop-1-yl)-isothiourea
-
0.05 mM, 28% vTopo RNase activity remaining
single-stranded M13 DNA
-
inhibits relation of negatively supercoiled DNA at 60-80°C
-
SN38
-
enzyme linker fluctuations can have an impact on SN38 binding by reducing the enzyme affinity for the drug. TOP1 mutations are involved in the development of SN38 resistance
SR proteins
-
inhibition of DNA nicking activity by SR proteins. Inhibition of the DNA nicking activity of Topo I by SRSF1 depends on RNA recognition motifs joined by a spacer, Topo I enzyme inhibition by spacer mutants, overview
-
Tax oncoprotein
-
from HTLV-1, inhibits DNA binding of topoisomerase I, which is the first step of the reaction catalyzed by the enzyme
-
tert-butyl 3-(4-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]-imidazol-2-yl)phenoxy)propylcarbamate
thiazole-containing oligopeptides
-
inhibitory effect increases with the number of thiazole units. Inhibitory properties of thiazole-containing oligopeptides containing 3 or 4 thiazole units are 3-10tímes better than those of distamycin A
-
Topostin B-553
-
interacts primarily with the enzyme and not with the substrate DNA
Topostin B-567
-
interacts primarily with the enzyme and not with the substrate DNA
topotecan hydrochloride
water soluble derivatives of camptothecin, hardly effective against bloodstream forms of Trypanosoma brucei
Tumor necrosis factor alpha
-
TNFalpha induces receptor-mediated apotosis. Receptor-mediated apoptosis induced by TNFalpha results in a very strong htopoI damage response, further indicating a general involvement of htopoI in apoptosis
-
tyrophostin AG-1387
-
the inhibitor alters the DNA relaxation process producing unique shapes of DNA molecules
zinc bis(2-[(E)-[(2,2-dichloro-4-oxo-4H-1,3,2-benzodioxastannin-6-yl)imino]methyl]phenolate)
-
-
[2,2',2'',2''',2'''',2''''',2''''''-([24-((2-[diethyl(methyl)ammonio]ethyl)sulfanyl)-14,19-dihydro-29H,31H-tetrabenzoporphine-2,3,9,10,16,17,23-heptayl-k4N29,N30,N31,N32]heptasulfanediyl)heptakis(N,N,N-trimethylethanaminiumato)(2-)]zinc(8+) octaiodide
-
-
(6aR,11aS)-11-[(4-methylphenyl)sulfonyl]-6,6a,11,11a-tetrahydro-5H-benzo[a]carbazole
-
binds selectively to PfTopoI
(6aR,11aS)-11-[(4-methylphenyl)sulfonyl]-6,6a,11,11a-tetrahydro-5H-benzo[a]carbazole
-
binds selectively to PfTopoI
(7aR,12aS)-5-methylidene-12-[(4-methylphenyl)sulfonyl]-7,7a,12,12a-tetrahydrobenzo[6,7]chromeno[4,3-b]indol-13(5H)-one
-
-
(7aR,12aS)-5-methylidene-12-[(4-methylphenyl)sulfonyl]-7,7a,12,12a-tetrahydrobenzo[6,7]chromeno[4,3-b]indol-13(5H)-one
-
-
(7aS,12aS)-10-methoxy-5-methylidene-5,7,7a,12a-tetrahydro-13H-[1]benzofuro[3,2-c]benzo[g]chromen-13-one
-
-
(7aS,12aS)-10-methoxy-5-methylidene-5,7,7a,12a-tetrahydro-13H-[1]benzofuro[3,2-c]benzo[g]chromen-13-one
-
-
(7aS,12aS)-11-methoxy-5-methylidene-13-oxo-5,7a,12a,13-tetrahydro-7H-[1]benzofuro[3,2-c]benzo[g]chromene-9-carbaldehyde
-
-
(7aS,12aS)-11-methoxy-5-methylidene-13-oxo-5,7a,12a,13-tetrahydro-7H-[1]benzofuro[3,2-c]benzo[g]chromene-9-carbaldehyde
-
-
(7aS,12aS)-5-methylidene-5,7,7a,12a-tetrahydro-13H-[1]benzofuro[3,2-c]benzo[g]chromen-13-one
-
-
(7aS,12aS)-5-methylidene-5,7,7a,12a-tetrahydro-13H-[1]benzofuro[3,2-c]benzo[g]chromen-13-one
-
-
10-Hydroxycamptothecin
-
camptothecin stabilizes Top1/dsDNA covalent complexes which ultimately results in cell death. Structure-activity-relationships for camptothecin and derivatives, modeling and calculation of interaction energies between bound camptothecin, and derivatives, and Top1/dsDNA, comparisons of different models, e.g. rotated +1 nucleoside and intercalated models, overview
2'-(4-(3,6,9,12,15,18-hexaoxahenicos-20-ynyloxy)phenyl)-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzo[d]imidazole
-
-
2'-(4-(3,6,9,12,15,18-hexaoxahenicos-20-ynyloxy)phenyl)-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzo[d]imidazole
-
-
2'-[4-([6-[(but-3-yn-1-yl)oxy]hexyl]oxy)phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
-
-
2'-[4-([6-[(but-3-yn-1-yl)oxy]hexyl]oxy)phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
-
-
2'-[4-[(but-3-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
-
-
2'-[4-[(but-3-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
-
-
2'-[4-[(heptadec-16-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
-
-
2'-[4-[(heptadec-16-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
-
-
2'-[4-[(hex-5-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
-
-
2'-[4-[(hex-5-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
-
-
2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
-
novel functionalities appended to the lactam side chain of the indenoisoquinolines. Development of indenoisoquinoline Top1 inhibitors where the di(methoxy) and methylenedioxy substituents on the aromatic nucleus are combined with previously utilized and novel heterocyclic lactam side chains in an effort to improve the anticancer activity of the indenoisoquinolines
2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
i.e. NSC314622
2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
-
i.e. NSC 314622
2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
-
-
2-(4-((1-(2-azidoethyl)-1H-1,2,3-triazol-4-yl)methoxy)-phenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazole
-
-
2-(4-((1-(2-azidoethyl)-1H-1,2,3-triazol-4-yl)methoxy)-phenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazole
-
-
2-(4-(2-(4-(4-ethynylphenyl)-1H-1,2,3-triazol-1-yl)ethoxy)-phenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazole
-
-
2-(4-(2-(4-(4-ethynylphenyl)-1H-1,2,3-triazol-1-yl)ethoxy)-phenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazole
-
-
2-(4-hydroxyphenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo-[d]imidazole-4-carboxylic acid
-
-
2-(4-hydroxyphenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo-[d]imidazole-4-carboxylic acid
-
-
2-(4-[[1-(6-azidohexyl)-1H-1,2,3-triazol-4-yl]methoxy]phenyl)-6-(4-methylpiperazin-1-yl)-1H-benzimidazole
-
-
2-(4-[[1-(6-azidohexyl)-1H-1,2,3-triazol-4-yl]methoxy]phenyl)-6-(4-methylpiperazin-1-yl)-1H-benzimidazole
-
-
3-(4-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-phenoxy)propan-1-amine
-
-
3-(4-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-phenoxy)propan-1-amine
-
-
5-(4-methylpiperazin-1-yl)-2-(4-(6-(prop-2-ynyloxy)-hexyloxy)phenyl)-1H-benzo[d]imidazole
-
-
5-(4-methylpiperazin-1-yl)-2-(4-(6-(prop-2-ynyloxy)-hexyloxy)phenyl)-1H-benzo[d]imidazole
-
-
6-(4-methylpiperazin-1-yl)-2'-(4-(10-(prop-2-ynyloxy)-decyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
-
-
6-(4-methylpiperazin-1-yl)-2'-(4-(10-(prop-2-ynyloxy)-decyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
-
-
6-(4-methylpiperazin-1-yl)-2'-(4-(12-(prop-2-ynyloxy)-dodecyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
-
-
6-(4-methylpiperazin-1-yl)-2'-(4-(12-(prop-2-ynyloxy)-dodecyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
-
-
6-(4-methylpiperazin-1-yl)-2'-(4-(6-(prop-2-ynyloxy)-hexyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
-
-
6-(4-methylpiperazin-1-yl)-2'-(4-(6-(prop-2-ynyloxy)-hexyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
-
-
6-(4-methylpiperazin-1-yl)-2'-(4-(8-(prop-2-ynyloxy)-octyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
-
-
6-(4-methylpiperazin-1-yl)-2'-(4-(8-(prop-2-ynyloxy)-octyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
-
-
6-(4-methylpiperazin-1-yl)-2-(4-(2-(4-(oct-7-ynyl)-1H-1,2,3-triazol-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazole
-
-
6-(4-methylpiperazin-1-yl)-2-(4-(2-(4-(oct-7-ynyl)-1H-1,2,3-triazol-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazole
-
-
6-(4-methylpiperazin-1-yl)-2-[4-[(prop-2-yn-1-yl)oxy]phenyl]-1H-benzimidazole
-
-
6-(4-methylpiperazin-1-yl)-2-[4-[(prop-2-yn-1-yl)oxy]phenyl]-1H-benzimidazole
-
-
7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxy-camptothecin
-
strong synergism between irinotecan and 5-fluorouracil
7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxy-camptothecin
-
i.e. irinotecan; review of clinical pharmacokinetics
8,9-dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-one
-
i.e. ARC-111
8,9-dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-one
-
i.e. ARC-111
8,9-dimethoxy-5-(2-N-methylaminoethyl)-2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-one
-
i.e. Genz-644282
8,9-dimethoxy-5-(2-N-methylaminoethyl)-2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-one
-
i.e. Genz-644282
Aminocatechol A-3253
-
Candida enzyme is more susceptible than the human enzyme
ATP
-
5 mM, 75% inhibition, ccomplete inhibition at 10 mM, regardless of Mg2+ concentration
Berberine
-
a polyheterocyclic class I topoisomerase inhibitor with a structure resembling the intercalant drug benzo[a]acridine. Several berberine analogues tested
Berberine
is a polyheterocyclic class I topoisomerase inhibitor with a structure resembling the intercalant drug benzo[a]acridine. Several berberine analogues tested
Berberine
-
is a polyheterocyclic class I topoisomerase inhibitor with a structure resembling the intercalant drug benzo[a]acridine. Several berberine analogues tested
camptothecin
-
in presence of the inhibitor, enzyme-supercoiled DNA complexes in which the enzyme is locked inside a relaxed region of the supercoiled DNA molecule are observed
camptothecin
-
DNA topoisomerase inhibitors are efficient and reversible inducers of premature senescence in normal cells
camptothecin
-
class I topoisomerase poison. Pentacyclic natural alkaloid produced by the plant Camptotheca accuminata
camptothecin
-
Topoisomerase I inhibitor added for measuring the inhibition of DNA relaxation
camptothecin
-
Camptothecin poisoning of TopIB induces accumulation of positively supercoiled DNA in G1- and S-phase yeast cells. Mechanism of camptothecin-induced toxicity derives from TopIB-dependent accumulation of positive supercoils
camptothecin
-
when CPT is added the cleavage religation equilibrium is shifted toward cleavage
camptothecin
-
-
camptothecin
-
a selective inhibitor of DNA topoisomerase I. Camptothecin activates the transcription of low-abundance antisense RNAs at the HIF-1alpha gene locus in human cancer cells in a topoisomerase I-dependent manner, likely due to sustained drug interference with transcription regulation mechanisms leading to a more open chromatin conformation and de-repression/activation of antisense transcription. Top1cc is then a specific DNA damage induced by the drug, damage and repair mechanisms, detailed overview
camptothecin
-
the natural compound reversibly binds the covalent Top1-DNA complex slowing down the religation of the cleaved DNA strand, thus inducing cell death
camptothecin
-
camptothecin stabilizes Top1/dsDNA covalent complexes which ultimately results in cell death. Structure-activity-relationships for camptothecin and derivatives, modeling and calculation of interaction energies between bound camptothecin, and derivatives, and Top1/dsDNA, comparisons of different models, e.g. rotated +1 nucleoside and intercalated models, overview
camptothecin
-
response to camptothecin-based treatment is dependent on hTopI activity, and reduction in activity as well as mutations in hTopI result in camptothecin resistance
camptothecin
-
class I topoisomerase poison. Pentacyclic natural alkaloid produced by the plant Camptotheca accuminata
camptothecin
-
Wild type and mutant sensitivity to camptothecin is determined in DNA cleavage assays. In vivo sensitivity to camptothecin also measured
camptothecin
-
Effect of CPT on the relaxation activity and equilibrium cleavage activity of fused topoisomerase I variants
camptothecin
-
the best characterized topoisomerase IB inhibitor. Ability of the naturally occurring flavones to stabilize the covalent topoisomerase IDNA complex in vitro and in living cells is similar to that of the known topoisomerase I inhibitor camptothecin (CPT)
camptothecin
-
class I topoisomerase poison. Pentacyclic natural alkaloid producted by the plant Camptotheca accuminata. Camptothecin is cytotoxic for the erythrocytic forms of Plasmodium falciparum
camptothecin
-
inhibition of wild-type enzyme, no inhibition of mutant enzymes N726S and N726S
camptothecin
-
this drug inhibits the rejoining reaction of DNAtopoisomerase I thus creating, in the presence of a denaturing agent, single-strand breaks and behaving like a single-strand nuclease. In vivo induction of camptothecin-dependent DNA topoisomerase I cleavage sites. Cells are treated for cleavage-site induction. Three different aliquots are incubated with 50, 100 or 200 microM camptothecin for 2 min at room temperature (25°C)
camptothecin
class I topoisomerase poison. Pentacyclic natural alkaloid produced by the plant Camptotheca accuminata
cisplatin
-
synergistic action between cisplatin and 7-ethyl-10-hydroxy-camptothecin in Kfr cells, a cisplatin resistant subline of the KF epithelial ovarian carcinoma cell line but not in the parent KF cells
cisplatin
-
presence of DNA adducts of bifunctional antitumor cisplatin or monodentate [PtCl(dien)]Cl in the substrate DNA inhibits eukaryotic top1 action, the adducts of cisplatin being more effective
coralyne
-
derivative of berberine has shown effectively combat Trypanosoma cruzi infection
dihydrobetulinic acid
-
catalytic inhibitor of topoisomerase I, inhibits the suicidal cleavage reaction
dihydrobetulinic acid
-
DHBA inhibits by preventing enzyme DNA binary complex formation. Inhibits also topoisomerase II
dihydrobetulinic acid
-
DHBA, pentacyclic triterpenoid and catalytic inhibitor of both topoisomerases I and II that antagonizes camptothecin-induced cleavage, do not induce the formation of SDS-K+ precipitable complex, when Leishmania donovani cells incubated for 3 h with the compound
diospyrin
-
promotes protein conformational changes that can affect the kinase activity of Top1 altering SR protein phosphorylation and alternative splicing
Fe2+
-
competes with Zn2+. TopA is an iron and zinc binding protein. Whereas the zinc-bound TopA is fully active to relax the negatively supercoiled DNA, the iron-bound TopA has little or no enzyme activity. The C-terminal zinc-binding region, but not the N-terminal fragment, of TopA, is involved in the iron binding
Fe2+
-
the iron-bound enzyme fails to relax the negatively supercoiled DNA, the iron-bound YrdD has very little or no binding activity for single-stranded DNA. Iron-bound YrdD cannot protect ssDNA from the DNase I digestion
irinotecan
-
a prodrug and it is activated by hydrolysis to the biologically active metabolite SN-38
irinotecan
-
i.e. CPT-11, a derivative of camptothecin and an anticancer agent in the treatment of metastatic colon cancer
irinotecan
-
topoisomerase I forms in vivo complexes with DNA substrates, the complexes are stabilized by irinotecan, which has DNA strand breaking ability, it leads to topisomerase poisoning and DNA damage, overview
irinotecan
water soluble derivatives of camptothecin, hardly effective against bloodstream forms of Trypanosoma brucei
KCl
-
can partially replace for NaCl in activation of enzyme forms MW 100000 and MW 110000
luteolin
-
naturally occurring flavone, binds to the free enzyme and also intercalates into the DNA at a very high concentration (300 mM) without binding to the minor grove
methyl (7aS,12aS)-5-methylidene-13-oxo-5,7a,12a,13-tetrahydro-7H-[1]benzofuro[3,2-c]benzo[g]chromene-9-carboxylate
-
-
methyl (7aS,12aS)-5-methylidene-13-oxo-5,7a,12a,13-tetrahydro-7H-[1]benzofuro[3,2-c]benzo[g]chromene-9-carboxylate
-
-
methyl 2-(4-Hydroxyphenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazole-4-carboxylate
-
-
methyl 2-(4-Hydroxyphenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazole-4-carboxylate
-
-
Mg2+
Effect of Mg2+ on bcTopo IIIbeta and ecTopo III-mediated DNA relaxation assays, high concentrations of Mg2+ (>2 mM) inhibit the relaxation
N-[2-(Dimethylamino)ethyl]carboxamide derivatives of fused tetracyclic quinolines and quinoxalines
-
-
-
N-[2-(Dimethylamino)ethyl]carboxamide derivatives of fused tetracyclic quinolines and quinoxalines
-
-
-
Na+
-
enzyme forms MW 100000 and MW 110000: inhibition above 300 mM NaCl. Enzyme form MW 150000: inhibition above 50 mM NaCl
NSC 314622
-
cytotoxicity results of its direct action upon topoisomerase 1 in cells
Par-4
-
tumor suppressor protein, prostate apoptosis response-4, binds to TOP1, via its leucine zipper domain, and prevents TOP1 interaction with the DNA
-
Par-4
-
tumor suppressor protein, prostate apoptosis response-4, binds to TOP1, via its leucine zipper domain, and prevents TOP1 interaction with the DNA
-
quercetin
i.e. 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-2,3-dihydro-4H-1-benzopyran-4-one
quercetin
-
naturally occurring flavone, binds to the free enzyme and also intercalates into the DNA at a very high concentration (300 mM) without binding to the minor grove
Rv1495
-
inhibits the DNA cleavage activity of MtbTopA as well as its function of relaxation of supercoiled DNA. An N-terminus fragment of Rv1495, designated Rv1495-N(29-56), lost mRNA cleavage activity, but retained a significant physical interaction and inhibitory effect on TopA proteins, overview. No DNA-binding activity is seen with Rv1495, even at a high protein concentration
-
Rv1495
-
inhibits the DNA cleavage activity of MsTopA as well as its function of relaxation of supercoiled DNA. An N-terminus fragment of Rv1495, designated Rv1495-N(29-56), lost mRNA cleavage activity, but retained a significant physical interaction and inhibitory effect on TopA proteins in vitro and in vivo. MsmTopA associates with Rv1495 in vivo because an obvious and a specific hybridization signal is detected. No DNA-binding activity is seen with Rv1495, even at a high protein concentration
-
tert-butyl 3-(4-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]-imidazol-2-yl)phenoxy)propylcarbamate
-
-
tert-butyl 3-(4-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]-imidazol-2-yl)phenoxy)propylcarbamate
-
-
topotecan
-
Camptothecin analogue, induce cell death by poisoning DNA topoisomerase I, topotecan significantly hinders topoisomerase-mediated DNA uncoiling, with a more pronounced effect on the removal of positive (overwound) versus negative supercoils. Significant activity against adult and paediatric solid tumours
topotecan
-
water-soluble camptothecin derivative, topotecan mimics a DNA base-pair and binds at the site of DNA cleavage by intercalating between the upstream (?1) and downstream (+1) base-pairs interacting also with the enzyme, acting as an interfacial uncompetitive inhibitor
[3-[(E)-2-carboxyethenyl]phenyl](dihydroxy)oxoantimonate(2-)
-
partial or complete inhibition of hTopo is only observed at relatively high compound concentrations in the range 5 to 20 microM
[3-[(E)-2-carboxyethenyl]phenyl](dihydroxy)oxoantimonate(2-)
-
shows significant inhibition of plasmid supercoil relaxation even at 100 nM concentrations. IC90 (compound concentration at which 90% or higher inhibition is observed) 0.1 microM, using high-throughput screen, relaxation inhibition 70%
additional information
-
no substantial inhibitory activity with BAY 50-7952, Ro-61-6653 and BAY 50-7950
-
additional information
-
poly(ADP)ribosylation leads to a loss in relaxing activity
-
additional information
-
non-camptothecin DNA topoisomerase I inhibitors in cancer therapy
-
additional information
-
no substantial inhibitory activity with BAY 50-7952, Ro-61-6653 and BAY 50-7950
-
additional information
-
toxicity of drugs targeted against topoisomerase I is directly related to the ability of the drug to stimulate topo I-dependent DNA cleavage
-
additional information
-
rebeccamycin and other indolcarbazole derivatives induces significant levels radiosensitization and exhibit efficiency in inducing TOP1-mediated DNA damage
-
additional information
-
to get a rough estimate of the preferred distance between two htopoI molecules a deoxyoligonucleotide with a defined length covalently attached (190 nts, the so-called suicide substrate L193s). Labelling of DNA attached to htopoI with 32P to determine the size of the attached DNA fragment more precisely
-
additional information
-
series of natural and synthetic protoberberine alkaloid evaluated for their inhibitory activities towards DNA topoisomerase I. Natural, monomeric protoberberine alkaloids and their mono-modified congeners show only minor activities. Most of the dimeric protoberberine alkaloids are highly active
-
additional information
biological results for substituted compounds revealed a disagreement between the structure-activity relationships of monomeric indenoisoquinoline and bisindenoisoquinoline as Top1 inhibitors, but cytotoxicity maintained for both series of compounds. Bisindenoisoquinoline to determine effect of indenoisoquinoline dimerization on cytotoxicity and Top1 inhibition. It is conceivable that it could exert antitumor activity by targeting DNA itself, apart from Top1
-
additional information
-
biological results for substituted compounds revealed a disagreement between the structure-activity relationships of monomeric indenoisoquinoline and bisindenoisoquinoline as Top1 inhibitors, but cytotoxicity maintained for both series of compounds. Bisindenoisoquinoline to determine effect of indenoisoquinoline dimerization on cytotoxicity and Top1 inhibition. It is conceivable that it could exert antitumor activity by targeting DNA itself, apart from Top1
-
additional information
-
indenoisoquinoline topoisomerase I (Top1) inhibitors. lactam substituents possessing nitrogen heterocycles can provide highly cytotoxic compounds with potent Top1 inhibition. Molecular modeling of these compounds in complex with DNA and Top1 suggests that some of the lactam substituents are capable of interacting with the DNA base pairs above and below the site of intercalation and/or with Top1 amino acid residues, resulting in increased biological activity
-
additional information
-
biphenyl-3,4'-diylbis(arsonic acid) and 5-(2,2-dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyl-6-[(4-methylphenyl)sulfonyl]tetrahydrofuro[2,3-d][1,3]dioxole show no inhibition even at compound concentrations of 20 microM
-
additional information
-
tumor suppressor p53 not only plays a key role in the regulation of the htopoI response to UV-C irradiation but also to treatment with colcemid
-
additional information
-
3-(4-methoxyphenyl)-1-(4'-hydroxyphenyl)-2-propen-1-one and3-(2-thienyl)-1-(4'-hydroxyphenyl)-2-propen-1-one do not interfere with the enzyme
-
additional information
-
determination for every cell line: GI50 (concentration inhibiting 50% net cell growth), TGI (total growth inhibition), and LC50 (concentration leading to 50% net cell death)
-
additional information
-
partial inhibition of the Top1-DNAadduct formation upon addition of poly(ADP ribose) polymerase 1 in the absence of NAD+ is shown, whereas in the presence of NAD+ formation of a high molecular weight product, most likely corresponding to poly(ADP) ribosylated Top1-DNA adduct, is observed
-
additional information
molecular design, synthesis and docking study of benz[b]oxepines and 12-oxobenzo[c]phenanthridinones, inhibitory potencies against topo 1, overview. Cytotoxic activity of inhibitors against human cancer cell lines, overview
-
additional information
-
cytotoxicity and mechanism of action of a series of substituted 9-aminoacridines is evaluated using topoisomerase I and cancer cell growth inhibition assays, overview
-
additional information
-
inhibitory and cytotoxic potencies of inhibitor compounds, in vivo activity in cancer cell lines, overview. No or poor inhibition by compounds 1-ethyl-3-(benzimidazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-4(1H)-quinolone, 1-ethyl-3-(benzimidazol-2-yl)-6-fluoro-7-(1-piperazin-1-yl)-1,8-naphthyridine-4(1H)-one, 6,8-bis(oxiran-2-ylmethoxy)benzo[b][1,8]naphthyridin-5(10H)-one, 6-hydroxy-8-(thiiran-2-ylmethoxy)benzo[b][1,8]naphthyridin-5(10H)-one, and 8-bis(thiiran-2-ylmethoxy)benzo[b][1,8]naphthyridin-5(10H)-one
-
additional information
-
inhibitory potencies and cytotoxicities versus human cancer cell lines of plant-originated triterpenoids and triterpenoid glycosides isolated from Aesculus pavia, diverse inactive compounds, overview
-
additional information
synthesis and inhibitory potency of a series of water-soluble aromathecins substituted at position 14 with diaminoalkanes of various lengths, that all show antiproliferative potency. Aromathecins with longer diaminoalkane substituents over 6Cs possess lower anti-top1 activity than their smaller counterparts with 2-4 Cs
-
additional information
-
design and synthesis of 60 2-thienyl-4-furyl-6-aryl pyridine derivatives, inhibitory potency and cytotoxicity analysis using human topoisomerase I and human cancer cell lines MCF-7, HeLa, DU145, and K562. The 2-(5-chlorothiophen-2-yl)-4-(furan-3-yl) moiety has an important role in displaying biological activities. No or poor inhibition by 2-(2-chlorophenyl)-4-(furan-2-yl)-6-(3-methylthiophen-2-yl) pyridine, 2-(4-chlorophenyl)-4-(furan-2-yl)-6-(3-methylthiophen-2-yl) pyridine, 2-(5-chlorothiophen-2-yl)-4-(furan-3-yl)-6-m-tolylpyridine, 2-(5-chlorothiophen-2-yl)-4-(furan-3-yl)-6-p-tolylpyridine, 2-(2-chlorophenyl)-6-(5-chlorothiophen-2-yl)-4-(furan-3-yl) pyridine, 2-(3-chlorophenyl)-6-(5-chlorothiophen-2-yl)-4-(furan-3-yl) pyridine, 2-(4-chlorophenyl)-6-(5-chlorothiophen-2-yl)-4-(furan-3-yl) pyridine, 6-(5-chlorothiophen-2-yl)-4-(furan-3-yl)-2, 2'-bipyridine, 6-(5-chlorothiophen-2-yl)-4-(furan-3-yl)-2,30-bipyridine, and 4-(5-chlorofuran-2-yl)-2-(4-chlorophenyl)-6-(5-chlorothiophen-2-yl) pyridine
-
additional information
-
inhibition mechanisms of cationic porphyrins and analogues, overview
-
additional information
-
inhibitor design and synthesis, anti-proliferative activity study in human cancer cell lines, effect of quinolone and naphthyridine derivatives on Top I activity, overview
-
additional information
cytotoxicities in cancer cells and topoisomerase I inhibitory activities of norindenoisoquinoline derivatives, molecular modeling, overview; inhibitor binding in the topoisomerase I-DNA covalent complex, molecular docking and quantum chemical calculations, overview
-
additional information
-
cytotoxicities in cancer cells and topoisomerase I inhibitory activities of norindenoisoquinoline derivatives, molecular modeling, overview; inhibitor binding in the topoisomerase I-DNA covalent complex, molecular docking and quantum chemical calculations, overview
-
additional information
-
evodiamine is slightly less cytotoxic than campothecin against breast MCF-7 carcinoma cells
-
additional information
-
a multiple metallation of the short nucleotide sequences on the scissile strand, immediately downstream of the cleavage site impedes the cleavage by top1
-
additional information
-
the benz[a]acridine analogues, noncharged bioisosteres of protoberberine alkaloids, are also Top1 inhibitors
-
additional information
-
inhibitory activity, cytotoxicity, and structure-activity relationship study of hydroxylated 2,4-diphenyl-6-aryl pyridines, overview. Hydroxyl substitution at 3- or 3'-position of phenyl ring on 2,4-diphenyl-6-aryl pyridines might be required in order to show significant topo inhibitory activity. No inhibition by 15, 35, and 31
-
additional information
-
various 5-amino group-substituted indeno[1,2-c]isoquinolines display potent topoisomerase I inhibitory activity as well as cytotoxicities against five different human tumor cell lines. Molecular modelling and docking using protein structure PDB ID 1SC7
-
additional information
-
topoisomerase I inhibition of glycosylated 2-phenyl-indoles, 2-phenyl-benzo[b]thiophenes and 2-phenyl-benzo[b]furans, overview. Analysis of cytotoxocity against three human non-tumor cell lines analyzed by the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) cell viability assay
-
additional information
-
topoisomerase I inhibitors act as anticancer drugs, overview. Bone marrow colony-forming unit, CFU, granulocyte macrophage CFU, and tumor cell CFU activity of topoisomerase I inhibitors, overview. CFU are bipotent hemopoietic stem cells. Human bone marrow colony-forming unit is more sensitive to the Top1 inhibitors than is mouse bone marrow colony-forming unit
-
additional information
-
molecular docking study, overview. No inhibition by 3-[3-[bis(2-hydroxyethyl)amino]-2-hydroxypropoxy]-1-hydroxy-9H-xanthen-9-one, 1-hydroxy-3-[2-hydroxy-3-[(3-hydroxypropyl)sulfanyl]propoxy]-9H-xanthen-9-one, 1-hydroxy-3-[2-hydroxy-3-[(2-hydroxyethyl)sulfanyl]propoxy]-9H-xanthen-9-one, 1-hydroxy-3-[2-hydroxy-3-(propylamino)propoxy]-9H-xanthen-9-one, 1-hydroxy-3-[2-hydroxy-3-(2-hydroxyethoxy)propoxy]-9H-xanthen-9-one, and 3-[3-[(2-chloroethyl)sulfanyl]-2-hydroxypropoxy]-1-hydroxy-9H-xanthen-9-one
-
additional information
-
synthesis of 2,4-diaryl chromenopyridines and evaluation of their topoisomerase II inhibitory activity, cytotoxicity, and structure-activity relationship, overview. 2-Furyl or 2-thienyl at 2- or 4-position of central pyridine is crucial in displaying topo I or II inhibitory activity and cytotoxicity. No inhibition by 18, 19,20, 21, 22, 23, 25, 29, 32, 33, and 35
-
additional information
-
Top1 can be inhibited by heterocyclic compounds such as indolocarbazoles and indenoisoquinolines. Carbohydrate and hydroxyl-containing side chains are essential for the biological activity of indolocarbazoles. Preparation and inhibitory potency of indenoisoquinolines substituted with short-chain alcohols, diols, and carbohydrates, cytotoxicity, Top1 poisoning activity of diol-substituted indenoisoquinolines is dependent upon stereochemistry, molecular modeling, docking studies, and structure-function relationships, overview. IC50 values for cytotoxic effects in human cancer cell lines, overview
-
additional information
-
binding constant values of heterobimetallic complexes including Sn2+ and Cu2+ or Zn2+, and ligand 5-{[(1E)-(2-hydroxyphenyl)methylene]amino}-2-hydroxybenzoic acid with the DNA, NMR and mass spectrometric structure analysis, inhibitory potencies, overview
-
additional information
-
no inhibition by etoposide. Design and semisynthetic reactions preparation of oleanane-type triterpene derivatives of Hibiscus sabdariffa plant-derived oleanolic acid based on docking studies, with topoisomerase I inhibitory activity, NMR spectroscopic structure analysis of the compounds, computer-assisted molecular modeling and docking, overview
-
additional information
-
7-acyl homocamptothecins as topoisomerase I inhibitors, inhibition of induced DNA cleavage and in vitro cytotoxicity against three cancer cell lines A-549, MDA-MB-435 and HCT-116, overview
-
additional information
-
design, synthesis, and evaluation of indenoisoquinolines that are dual inhibitors of both tyrosyl-DNA phosphodiesterase I and Top1, structure-activity relationships, ctotoxic activities, and molecular modeling, overview
-
additional information
-
inhibitor design and evaluation, DNA cleavage inhibition and cytotoxic activities, docking study, overview
-
additional information
-
isolation of six synthetic isoflavonoid derivatives that dock in the binding site of inhibitors camptothecin and topotecan inside the enzyme, no inhibition by LQB223, docking and molecular dynamics simulations, overview
-
additional information
-
the detection method termed rolling circle enhanced enzyme activity detection allows measurement of hTopI cleavage-religation activity at the single molecule level, and may be used to detect posttranslational enzymatic differences influencing camptothecin response
-
additional information
-
intercalation of indolocarbazole drugs in the DNA molecule is reinforced by the existance of the sugar moiety, which helps to stabilize the insertion complex by binding with the major groove of the ternary duplex DNA. The presence of chlorine atoms disminishes topoisomerase I inhibition
-
additional information
-
trapping of the covalent complex between LdTop1 and DNA by camptothecin resides in a pentapeptide placed upwards Arg-180, increases the sensitivity to the poison
-
additional information
-
Novel series of anthra[1,2-d]imidazole-6,11-dione derivatives, benzimidazole and anthraquinone derivatives are known topoisomerase inhibitors, synthesized nine imidazole-fused anthraquinone derivatives. The inhibition activity of the drugs is compared to that of the standard topo I poison cpt. Compounds with tetrazole, imidazole, or morpholine side chains exhibit potent inhibition activity against the parasitic enzyme, with activity significantly higher than that shown by camptothecin
-
additional information
-
Comparisons of topoisomerase I-mediated DNA cleavage induced by flavones and camptothecin. The rates of stabilization of cleavable complex by the flavones are 2-to 3fold reduced compared with that of camptothecin. Analysis of drug induced covalent topoisomerase IDNA complex formation in Leishmania donovani promastigotes by KCl-SDS precipitation assay. Treatment of the cells with baicalein, luteolin and quercetin for 5 h significantly increases the SDS-K+ precipitable complex compared with the untreated control cells. Relief of inhibition on dilution suggests that the selected flavones are acting reversibly against topoisomerase I. Fluorescence spectroscopy used to check directly the binding of luteolin, baicalein and quercetin to the enzyme (LdTOP1LS). Fluorescence titration data reveal that these selected flavones interact with free enzyme and perhaps explain for stronger inhibition in the enzymedrug pre-incubation experiments. Ability of the selected flavones to displace ethidium bromide from DNA is determined by a fluorescence emission assay. Effect of flavones on single turnover cleavage and religation activity measured, interaction of these flavones with enzyme during trans-esterification reaction with DNA is a pre-requirement for the stabilization of topoisomerase I-cleavable complex and subsequently inhibiting the religation step
-
additional information
-
elsamicin A might not be a topoisomerase I inhibitor, but behaves as an intercalating agent in DNA unwinding
-
additional information
-
PARP inhibitors prevent the glutamate, but not GABA, induced decrease in topo I activity
-
additional information
-
topoisomerase I inhibitors act as anticancer drugs, overview. Bone marrow colony-forming unit, CFU, granulocyte macrophage CFU, and tumor cell CFU activity of topoisomerase I inhibitors, overview. CFU are bipotent hemopoietic stem cells. Human bone marrow colony-forming unit is more sensitive to the Top1 inhibitors than is mouse bone marrow colony-forming unit
-
additional information
oligonucleotides containing the specific recognition sequence inhibit the activity of the enzyme, as well as the monoclonal antibody 2F3G4, developed against MstopoI inhibited the relaxation activity of the enzyme. No inhibition with non-specific oligonucleotides
-
additional information
-
oligonucleotides containing the specific recognition sequence inhibit the activity of the enzyme, as well as the monoclonal antibody 2F3G4, developed against MstopoI inhibited the relaxation activity of the enzyme. No inhibition with non-specific oligonucleotides
-
additional information
-
isolation of six synthetic isoflavonoid derivatives that dock in the binding site of inhibitors camptothecin and topotecan inside the enzyme, cytotoxicity in CQ-sensitive (3D7) or CQ-resistant (W2) parasites, overview
-
additional information
-
study of the action of DNA topoisomerase-targeted drugs
-
additional information
no inhibition by nalidixic acid and etoposide, and by spermidine
-
additional information
-
no inhibition by nalidixic acid and etoposide, and by spermidine
-
additional information
-
extracts from Greek domestic grapes are effective in inhibiting wheat germ topoisomerase I activity
-
additional information
-
using molecular beacon assay for topo I to blindly screen a 1990-member small-molecule library and to identify several specific inhibitors of the poxvirus topoisomerase
-
additional information
-
Poxviridae topoisomerase IB is insensitive to camptothecin. Because Poxviridae topoisomerase IB is not essential for the viral life cycle, the preferred strategy would be to develop agents that act as topoisomerase poisons rather than catalytic inhibitors. By trapping the cleavage complex, drug treatment could either fragment the viral genome or block early transcription by placing a covalently attached protein in the path of RNA polymerase. High-throughput screen identified nineteen compounds with activity against vaccinia topoisomerase IB with IC50 values in the low micromolar range and displayed no inhibition of human topoisomerase IB
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-ethylKuQuinone
-
synthesis of the pentacyclic-diquinoid synthetic compound, overview. It efficiently inhibits the cleavage step of the enzyme reaction fitting well into the catalytic site. When incubated with the binary topoisomerase-DNA cleaved complex, the compound helps the enzyme to remove itself from the cleaved DNA and close the DNA gap, increasing the religation rate. The compound also induces the religation of the stalled enzyme-camptothecin-DNA ternary complex. The religation enhancement is due to the presence on the compound of two oxygen atoms that act as hydrogen acceptors. This property facilitates the deprotonation of the 5 DNA end. Docking and molecular modeling, overview
glycerol
-
high concentrations increase the efficiency of the DNA relaxation reaction
nitrite
-
acidic nitrite enhanced the bactericidal effect of stabilized topoisomerase I cleavage complex
additional information
-
enzyme is posttranslationally modified and presumably regulated by phosphorylation
-
additional information
-
enzyme is posttranslationally modified and presumably regulated by phosphorylation
-
additional information
-
the lack of stimulation by ssDNA binding protein SSB suggests that ssDNA regions required for SsTop3 binding are stably exposed in the negatively supercoiled substrate at the high reaction temperature, even in the absence of ssDNA binding protein SSB
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
analysis of kinetic and thermodynamic parameters for strand annealing of purified vaccinia Topo I-DNA covalent complex containing a single-strand overhang, and comparison to the same overhang duplex in the absence of vTopo, overview
-
additional information
additional information
-
dissociation constants obtained for binding of wild-type EcTOP1, R169A, R173A and Y177S mutant enzymes to 3'-labeled 59 base hairpin oligonucleotide substrates, Oligo C, Oligo A and Oligo G, overview
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000063
camptothecin
-
with 0.63 microM camptothecin or more numerous shifted htopoI bands detected
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0163
11-acetyl-10-hydroxy-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.00715
11-[2-(dimethylamino)ethoxy]-2-methyl-4H-naphtho[2,3-h]chromene-4,7,12-trione
Homo sapiens
-
-
0.05
2'-(4-(3,6,9,12,15,18-hexaoxahenicos-20-ynyloxy)phenyl)-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzo[d]imidazole
Escherichia coli
-
IC50 above 0.05 mM, pH and temperature not specified in the publication
0.00663 - 0.05
2'-[4-([6-[(but-3-yn-1-yl)oxy]hexyl]oxy)phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
0.0055 - 0.2541
2'-[4-[(but-3-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
0.00247 - 0.05
2'-[4-[(heptadec-16-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
0.00457 - 0.05
2'-[4-[(hex-5-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
0.0215 - 0.05
2-(4-[[1-(6-azidohexyl)-1H-1,2,3-triazol-4-yl]methoxy]phenyl)-6-(4-methylpiperazin-1-yl)-1H-benzimidazole
0.00266 - 0.00511
2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)-N-[2-methyl-1-(morpholin-4-ylcarbonyl)propyl]acetamide
0.00126 - 0.00223
2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)-N-[3-methyl-1-[(4-methylpiperazin-1-yl)carbonyl]butyl]acetamide
0.00495
3,10-dibromo-11-hydroxy-2-methyl-4H-naphtho[2,3-h]chromene-4,7,12-trione
Homo sapiens
-
-
0.0012
3,3'-diindolylmethane
Leishmania donovani
-
potent inhibitor of Leishmania donovani topoisomerase I
0.0015
4,11-bis[(2-aminoethyl)amino]-1H-naphtho[2,3-f]indole-5,10-dione
Homo sapiens
-
IC50 values 0.0005 mM to 0.0015 mM for 4,11-bis([2-[(2-hydroxyethyl)amino]ethyl]amino)-1H-naphtho[2,3-f]indole-5,10-dione, 0.0015 mM to 0.0035 mM for 4,11-bis[[2-(methylamino)ethyl]amino]-1H-naphtho[2,3-f]indole-5,10-dione, above 0.0035 mM for 4,11-bis[[2-(dimethylamino)ethyl]amino]-1H-naphtho[2,3-f]indole-5,10-dione
0.01224 - 0.05
6-(4-methylpiperazin-1-yl)-2'-(4-(10-(prop-2-ynyloxy)-decyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
0.004 - 0.05
6-(4-methylpiperazin-1-yl)-2'-(4-(12-(prop-2-ynyloxy)-dodecyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
0.0032 - 0.05
6-(4-methylpiperazin-1-yl)-2'-(4-(6-(prop-2-ynyloxy)-hexyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
0.0028 - 0.05
6-(4-methylpiperazin-1-yl)-2'-(4-(8-(prop-2-ynyloxy)-octyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
0.019 - 0.0235
ethyl 10-amino-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
0.0011 - 0.0208
ethyl 10-bromo-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
0.0022 - 0.0199
ethyl 10-chloro-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
0.0012 - 0.0062
ethyl 10-fluoro-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
0.0233 - 0.0238
ethyl 10-hydroxy-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
0.00927 - 0.01165
ethyl 10-methyl-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
0.01643 - 0.02341
ethyl 7-amino-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
0.002 - 0.0103
ethyl 7-bromo-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
0.0021 - 0.00737
ethyl 7-chloro-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
0.00137 - 0.00701
ethyl 7-fluoro-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
0.0072
ethyl 7-hydroxy-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for GLC-82 cells
0.00022 - 0.0145
ethyl 7-methyl-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
0.00213 - 0.00288
methyl N-[(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetyl]glycinate
0.00109 - 0.00288
N-[1-benzyl-2-(4-ethylpiperazin-1-yl)-2-oxoethyl]-2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetamide
0.00244 - 0.00794
N-[1-[(4-ethylpiperazin-1-yl)carbonyl]-3-methylbutyl]-2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetamide
0.0000063
nick-containing oligonucleotide, nick-containing oligonucleotides
Homo sapiens
-
-
-
0.01029
11-acetyl-10-amino-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for NCI-H460 cells
0.0103
11-acetyl-10-amino-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.0158
11-acetyl-10-amino-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for HL-60 cells
0.0002
11-acetyl-10-bromo-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for NCI-H460 cells
0.00156
11-acetyl-10-bromo-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for HL-60 cells
0.00468
11-acetyl-10-bromo-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.0124
11-acetyl-10-bromo-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for MCF-7 cells
0.0015
11-acetyl-10-chloro-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for NCI-H460 cells
0.0161
11-acetyl-10-chloro-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.0161
11-acetyl-10-chloro-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for MCF-7 cells
0.022
11-acetyl-10-chloro-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for HL-60 cells
0.00139
11-acetyl-10-fluoro-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for HL-60 cells
0.00675
11-acetyl-10-fluoro-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for NCI-H460 cells
0.00928
11-acetyl-10-fluoro-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for MCF-7 cells
0.0127
11-acetyl-10-fluoro-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.00663
2'-[4-([6-[(but-3-yn-1-yl)oxy]hexyl]oxy)phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
Escherichia coli
-
pH and temperature not specified in the publication
0.05
2'-[4-([6-[(but-3-yn-1-yl)oxy]hexyl]oxy)phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
Homo sapiens
-
IC50 above 0.05 mM, pH and temperature not specified in the publication
0.0055
2'-[4-[(but-3-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
Escherichia coli
-
pH and temperature not specified in the publication
0.2541
2'-[4-[(but-3-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
Homo sapiens
-
pH and temperature not specified in the publication
0.00247
2'-[4-[(heptadec-16-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
Escherichia coli
-
pH and temperature not specified in the publication
0.05
2'-[4-[(heptadec-16-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
Homo sapiens
-
IC50 above 0.05 mM, pH and temperature not specified in the publication
0.00457
2'-[4-[(hex-5-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
Escherichia coli
-
pH and temperature not specified in the publication
0.05
2'-[4-[(hex-5-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
Homo sapiens
-
IC50 above 0.05 mM, pH and temperature not specified in the publication
0.0215
2-(4-[[1-(6-azidohexyl)-1H-1,2,3-triazol-4-yl]methoxy]phenyl)-6-(4-methylpiperazin-1-yl)-1H-benzimidazole
Escherichia coli
-
pH and temperature not specified in the publication
0.05
2-(4-[[1-(6-azidohexyl)-1H-1,2,3-triazol-4-yl]methoxy]phenyl)-6-(4-methylpiperazin-1-yl)-1H-benzimidazole
Homo sapiens
-
IC50 above 0.05 mM, pH and temperature not specified in the publication
0.00266
2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)-N-[2-methyl-1-(morpholin-4-ylcarbonyl)propyl]acetamide
Homo sapiens
-
for HT-29 cells
0.00511
2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)-N-[2-methyl-1-(morpholin-4-ylcarbonyl)propyl]acetamide
Homo sapiens
-
for A549 cells
0.00126
2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)-N-[3-methyl-1-[(4-methylpiperazin-1-yl)carbonyl]butyl]acetamide
Homo sapiens
-
for HT-29 cells
0.00184
2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)-N-[3-methyl-1-[(4-methylpiperazin-1-yl)carbonyl]butyl]acetamide
Homo sapiens
-
for A549 cells
0.00194
2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)-N-[3-methyl-1-[(4-methylpiperazin-1-yl)carbonyl]butyl]acetamide
Homo sapiens
-
for MCF-7 cells
0.00223
2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)-N-[3-methyl-1-[(4-methylpiperazin-1-yl)carbonyl]butyl]acetamide
Homo sapiens
-
for Bel-7402 cells
0.01224
6-(4-methylpiperazin-1-yl)-2'-(4-(10-(prop-2-ynyloxy)-decyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
Escherichia coli
-
pH and temperature not specified in the publication
0.05
6-(4-methylpiperazin-1-yl)-2'-(4-(10-(prop-2-ynyloxy)-decyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
Homo sapiens
-
IC50 above 0.05 mM, pH and temperature not specified in the publication
0.004
6-(4-methylpiperazin-1-yl)-2'-(4-(12-(prop-2-ynyloxy)-dodecyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
Escherichia coli
-
pH and temperature not specified in the publication
0.05
6-(4-methylpiperazin-1-yl)-2'-(4-(12-(prop-2-ynyloxy)-dodecyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
Homo sapiens
-
IC50 above 0.05 mM, pH and temperature not specified in the publication
0.0032
6-(4-methylpiperazin-1-yl)-2'-(4-(6-(prop-2-ynyloxy)-hexyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
Escherichia coli
-
pH and temperature not specified in the publication
0.05
6-(4-methylpiperazin-1-yl)-2'-(4-(6-(prop-2-ynyloxy)-hexyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
Homo sapiens
-
IC50 above 0.05 mM, pH and temperature not specified in the publication
0.0028
6-(4-methylpiperazin-1-yl)-2'-(4-(8-(prop-2-ynyloxy)-octyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
Escherichia coli
-
pH and temperature not specified in the publication
0.05
6-(4-methylpiperazin-1-yl)-2'-(4-(8-(prop-2-ynyloxy)-octyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
Homo sapiens
-
IC50 above 0.05 mM, pH and temperature not specified in the publication
0.0122
6-acetyl-7-amino-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.00021
6-acetyl-7-bromo-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for HL-60 cells
0.00201
6-acetyl-7-bromo-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.00215
6-acetyl-7-bromo-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for NCI-H460 cells
0.00019
6-acetyl-7-chloro-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for HL-60 cells
0.00023
6-acetyl-7-chloro-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for NCI-H460 cells
0.00685
6-acetyl-7-chloro-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.00783
6-acetyl-7-chloro-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for MCF-7 cells
0.00017
6-acetyl-7-fluoro-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for HL-60 cells
0.00231
6-acetyl-7-fluoro-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for MCF-7 cells
0.00526
6-acetyl-7-fluoro-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.0176
6-acetyl-7-hydroxy-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for MCF-7 cells
0.0195
6-acetyl-7-hydroxy-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.02485
6-acetyl-7-hydroxy-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for NCI-H460 cells
0.0015
baicalein
Leishmania donovani
-
LdTOP1LS pre-incubated separately with different concentrations for 5 min at 37°C in relaxation buffer followed by addition of pBluescript(SK+) DNA and further incubated for 15 min at 37°C
0.009
baicalein
Leishmania donovani
-
Quantitative representation of enzyme inhibition in the presence of flavones in relaxation experiments
0.00009
epirubicin
Homo sapiens
-
wild type enzyme from HCT-116 cells, pH and temperature not specified in the publication
0.00011
epirubicin
Homo sapiens
-
wild type enzyme from LoVo cells, pH and temperature not specified in the publication
0.00018
epirubicin
Homo sapiens
-
wild type enzyme from HT-29 cells, pH and temperature not specified in the publication
0.0002
epirubicin
Homo sapiens
-
mutant enzyme R364K/G717R from HCT-116 cells, pH and temperature not specified in the publication
0.019
ethyl 10-amino-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for NCI-H460 cells
0.0235
ethyl 10-amino-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for GLC-82 cells
0.0011
ethyl 10-bromo-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for GLC-82 cells
0.0024
ethyl 10-bromo-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for NCI-H460 cells
0.01147
ethyl 10-bromo-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for HL-60 cells
0.0208
ethyl 10-bromo-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for MCF-7 cells
0.0022
ethyl 10-chloro-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for NCI-H460 cells
0.00973
ethyl 10-chloro-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for GLC-82 cells
0.01542
ethyl 10-chloro-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for HL-60 cells
0.0199
ethyl 10-chloro-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for MCF-7 cells
0.0012
ethyl 10-fluoro-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for NCI-H460 cells
0.0017
ethyl 10-fluoro-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for GLC-82 cells
0.00551
ethyl 10-fluoro-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for HL-60 cells
0.0062
ethyl 10-fluoro-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for MCF-7 cells
0.0233
ethyl 10-hydroxy-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for NCI-H460 cells
0.0238
ethyl 10-hydroxy-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for GLC-82 cells
0.00927
ethyl 10-methyl-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for GLC-82 cells
0.01165
ethyl 10-methyl-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for HL-60 cells
0.00088
ethyl 5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for HL-60 cells
0.00096
ethyl 5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for MCF-7 cells
0.0019
ethyl 5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for NCI-H460 cells
0.0024
ethyl 5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for GLC-82 cells
0.00638
ethyl 5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for MCF-7 cells
0.01445
ethyl 5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for HL-60 cells
0.01643
ethyl 7-amino-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for HL-60 cells
0.01758
ethyl 7-amino-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for NCI-H460 cells
0.0209
ethyl 7-amino-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for MCF-7 cells
0.02341
ethyl 7-amino-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for GLC-82 cells
0.002
ethyl 7-bromo-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for NCI-H460 cells
0.00932
ethyl 7-bromo-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for HL-60 cells
0.0103
ethyl 7-bromo-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for MCF-7 cells
0.0021
ethyl 7-chloro-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for NCI-H460 cells
0.00652
ethyl 7-chloro-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for HL-60 cells
0.00737
ethyl 7-chloro-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for MCF-7 cells
0.00137
ethyl 7-fluoro-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for HL-60 cells
0.00701
ethyl 7-fluoro-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for MCF-7 cells
0.00022
ethyl 7-methyl-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for HL-60 cells
0.00183
ethyl 7-methyl-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for GLC-82 cells
0.0145
ethyl 7-methyl-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for MCF-7 cells
0.0018
etoposide
Homo sapiens
-
wild type enzyme from LoVo cells, pH and temperature not specified in the publication
0.0044
etoposide
Homo sapiens
-
mutant enzyme R364K/G717R from HCT-116 cells, pH and temperature not specified in the publication
0.0063
etoposide
Homo sapiens
-
wild type enzyme from HCT-116 cells, pH and temperature not specified in the publication
0.0099
etoposide
Homo sapiens
-
wild type enzyme from HT-29 cells, pH and temperature not specified in the publication
0.0025
luteolin
Leishmania donovani
-
LdTOP1LS pre-incubated separately with different concentrations for 5 min at 37°C in relaxation buffer followed by addition of pBluescript(SK+) DNA and further incubated for 15 min at 37°C
0.014
luteolin
Leishmania donovani
-
Quantitative representation of enzyme inhibition in the presence of flavones in relaxation experiments
0.00213
methyl N-[(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetyl]glycinate
Homo sapiens
-
for A549 cells
0.00223
methyl N-[(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetyl]glycinate
Homo sapiens
-
for MCF-7 cells
0.00288
methyl N-[(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetyl]glycinate
Homo sapiens
-
for HT-29 cells
0.00109
N-[1-benzyl-2-(4-ethylpiperazin-1-yl)-2-oxoethyl]-2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetamide
Homo sapiens
-
for HCT-8 cells
0.00186
N-[1-benzyl-2-(4-ethylpiperazin-1-yl)-2-oxoethyl]-2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetamide
Homo sapiens
-
for A549 cells
0.00191
N-[1-benzyl-2-(4-ethylpiperazin-1-yl)-2-oxoethyl]-2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetamide
Homo sapiens
-
for Bel-7402 cells
0.00191
N-[1-benzyl-2-(4-ethylpiperazin-1-yl)-2-oxoethyl]-2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetamide
Homo sapiens
-
for MCF-7 cells
0.00288
N-[1-benzyl-2-(4-ethylpiperazin-1-yl)-2-oxoethyl]-2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetamide
Homo sapiens
-
for HT-29 cells
0.00244
N-[1-[(4-ethylpiperazin-1-yl)carbonyl]-3-methylbutyl]-2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetamide
Homo sapiens
-
for MCF-7 cells
0.00348
N-[1-[(4-ethylpiperazin-1-yl)carbonyl]-3-methylbutyl]-2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetamide
Homo sapiens
-
for HT-29 cells
0.00794
N-[1-[(4-ethylpiperazin-1-yl)carbonyl]-3-methylbutyl]-2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetamide
Homo sapiens
-
for A549 cells
0.00002
NSC 725776
Homo sapiens
-
wild type enzyme from LoVo cells, pH and temperature not specified in the publication
0.00003
NSC 725776
Homo sapiens
-
wild type enzyme from HT-29 cells, pH and temperature not specified in the publication
0.00006
NSC 725776
Homo sapiens
-
wild type enzyme from HCT-116 cells, pH and temperature not specified in the publication
0.047
NSC 725776
Homo sapiens
-
mutant enzyme R364K/G717R from HCT-116 cells, pH and temperature not specified in the publication
0.00006
NSC 743400
Homo sapiens
-
wild type enzyme from LoVo cells, pH and temperature not specified in the publication
0.00007
NSC 743400
Homo sapiens
-
wild type enzyme from HT-29 cells, pH and temperature not specified in the publication
0.00017
NSC 743400
Homo sapiens
-
wild type enzyme from HCT-116 cells, pH and temperature not specified in the publication
0.047
NSC 743400
Homo sapiens
-
mutant enzyme R364K/G717R from HCT-116 cells, pH and temperature not specified in the publication
0.0055
quercetin
Leishmania donovani
-
LdTOP1LS pre-incubated separately with different concentrations for 5 min at 37°C in relaxation buffer followed by addition of pBluescript(SK+) DNA and further incubated for 15 min at 37°C
0.017
quercetin
Leishmania donovani
-
Quantitative representation of enzyme inhibition in the presence of flavones in relaxation experiments
0.00002
SN-38
Homo sapiens
-
wild type enzyme from LoVo cells, pH and temperature not specified in the publication
0.00005
SN-38
Homo sapiens
-
wild type enzyme from HCT-116 cells, pH and temperature not specified in the publication
0.00013
SN-38
Homo sapiens
-
wild type enzyme from HT-29 cells, pH and temperature not specified in the publication
0.0034
SN-38
Homo sapiens
-
mutant enzyme R364K/G717R from HCT-116 cells, pH and temperature not specified in the publication
additional information
additional information
Homo sapiens
-
for a mixture of ethyl 5,12-dioxo-5,12-dihydroindolizino[2,3-g]isoquinoline-6-carboxylate and ethyl 5,12-dioxo-5,12-dihydroindolizino[3,2-g]isoquinoline-11-carboxylate the IC50 values are 0.00936 mM for GLC-82 cells, 0.01170 mM for MCF-7 cells, 0.0022 mM for NCI-H460 cells, and 0.01743 mM for HL-60 cells. For a mixture of 5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carbonitrile and 5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline-11-carbonitrile the IC50 values are 0.01267 mM for HL-60 cells, 0.00250 mM for GLC-82 cells, 0.00156 mM for MCF-7 cells, and 0.00016 mM for NCI-H460 cells
-
additional information
additional information
Homo sapiens
GI50 values (the concentrations corresponding to 50% growth inhibition) for the different inhibitors with the different cell lines listed
-
additional information
additional information
Homo sapiens
-
IC50 value for 11-methoxy-2-methyl-4H-naphtho[2,3-h]chromene-4,7,12-trione is more than 0.260 mM, for 1-hydroxy-8-methoxyanthracene-9,10-dione, 5,9,11-trimethoxy-2-methyl-4H-naphtho[2,3-h]chromene-4,7,12-trione, 11-methoxy-2-phenyl-4H-naphtho[2,3-h]chromene-4,7,12-trione and 1-[2-(dimethylamino)ethoxy]-8-methoxyanthracene-9,10-dione more than 0.100 mM
-
additional information
additional information
Homo sapiens
-
2-thienyl-4-furyl-6-aryl pyridine derivatives, IC50 values in cytotoxicity assays in cancer cell lines, overview
-
additional information
additional information
Homo sapiens
-
IC50 values of inhibitors in different cancer cell lines in vivo, effects after transient transfection, overview
-
additional information
additional information
Homo sapiens
-
inhibitor IC50 values in vivo in different cancer cell lines, overview
-
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
quantitative detection of enzyme activity in Hut 78 cells over several hours after transient induction by interleukin-2, overview
additional information
5000 U, with one unit topoisomerase activity defined as the amount of enzyme required to relax 50% of supercoiled pGEM3zf(-) DNA (200 ng) for 30 min at 37°C, pH 8.0, in the presence of 5 mM of MgCl2, recombinant enzyme
additional information
-
5000 U, with one unit topoisomerase activity defined as the amount of enzyme required to relax 50% of supercoiled pGEM3zf(-) DNA (200 ng) for 30 min at 37°C, pH 8.0, in the presence of 5 mM of MgCl2, recombinant enzyme
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5
-
While wild-type enzyme is active at pH 5.5, S10A mutant requires pH to be elevated to 6.0 for relaxation activity to be observed, suggesting a protonation event between pH 5.56.0 in the S10A mutant to influence the activity
7.5
7.5 - 8.5
7.8
7.9
8.5
-
mutant enzymes H365Q, H365A, H365N, H365D, H365E and H365R, relaxation activity
9.8
optimal pH for the bcTopo IIIbeta-mediated superhelical DNA relaxation is 9.8 or higher
additional information
additional information
When glycerol is used as the cryoprotectant (Form II) at a pH at or below 7, enzyme molecules in the asymmetric unit are found in different conformations, with each one deviating from the apo-form of Escherichia coli topoisomerase III. Crystals soaked in 25% glycerol and at pH 8.0 result in a third structure revealing one molecule in the open conformation with the ssDNA fully binding and the other molecule in an intermediate conformation, where the enzyme is mostly closed, the ssDNA is also in an intermediate conformation between the closed and open forms, and a helix forming part of the groove has shifted
additional information
-
When glycerol is used as the cryoprotectant (Form II) at a pH at or below 7, enzyme molecules in the asymmetric unit are found in different conformations, with each one deviating from the apo-form of Escherichia coli topoisomerase III. Crystals soaked in 25% glycerol and at pH 8.0 result in a third structure revealing one molecule in the open conformation with the ssDNA fully binding and the other molecule in an intermediate conformation, where the enzyme is mostly closed, the ssDNA is also in an intermediate conformation between the closed and open forms, and a helix forming part of the groove has shifted
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5 - 8
-
pH 5: 25% of maximal activity, pH 6: about 50% of maximal activity, pH 8: about 50% of maximal activity
5.5 - 8
solved crystal structures of wild-type Escherichia coli topoisomerase III bind to an eight-base ssDNA molecule in three different pH environments. A low pH of the crystallization environment (pH 5.5) inhibits the wild-type enzyme from cleaving its substrate. At pH 7.0, the overall conformation of each molecule in the asymmetric unit remains the same as that observed at pH 5.5. In the pH 8 structure, one of the molecules is in the open conformation and the other in the intermediate conformation, but no cleavage is observed. In all, there are seven different closed structures: one of the molecules in the asymmetric unit in each of the five different conditions (Form I pH 5.5 and 7.0 and Form II pH 5.5, 7.0, and 8.0), and two additional closed complexes in the glucose or Form I crystals. At a pH below 8, crystals cryo-protected with glycerol show one monomer in the closed conformation and one in the open conformation
5.5 - 9.5
6 - 9.5
-
cleavage rates of both LdTOPIL-fus-S and the H453Q mutant LdTOPIL-fus-S proteins at the following pH values: 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, and 9.5 measured. Effect of pH on suicide cleavage rate for LdTOPIL-fus-S and H632Q mutants of LdTOPIL-fus-S proteins
6.5 - 10.4
bcTopo IIIbeta relaxes supercoiled DNA in a pH dependent manner. Distributive patterns of partially relaxed topoisomers appear with an increase of pH. Comparison with ecTopo III Escherichia coli topoisomerase characteristics
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
30
30 - 37
37
90
-
highest activity based on the amount of positive supercoils introduced into DNA
37
-
assay at
37
-
At 37°C, E1 double hexamers are preferentially formed. The addition of ATP/Mg2+ stimulated the binding activity of E1 at 37°C, but not at 25°C. Optimal stimulation of binding of E1 by Topo I to origin DNA occurred at 37°C in the presence of ATP/Mg 2+
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25 - 37
-
The effects of ATP/Mg2+ and temperature on the ability of E1 to bind origin DNA in the presence and absence of Topo I is shown. Increasing amounts of E1 were incubated with radiolabeled PV origin DNA at 37°C or 25°C in the presence or absence of ATP/Mg2+
37 - 65
Effect of temperature on bcTopo IIIbeta mediated DNA relaxation assay. Comparison with ecTopo III Escherichia coli topoisomerase characteristics
55 - 75
-
55°C: about 90% of maximal activity, 75°C: about 60% of maximal activity. No activity below 37°C
60 - 90
-
highest activity based on the amount of positive supercoils introduced into DNA is 90°C. The level of positive superturns introduced by TopR1 diminishes with decreasing temperature. This diminution is regular and is about four supercoils every 5°C. At 60 °C, TopR1 is essentially able to relax the negatively supercoiled substrate
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
overall charge difference observed, proposed that the protein regions bearing these differences may contribute to establishing ionic interactions that hold the subunits together
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Drosophila sp. (in: flies)
camptothecin producing plant has Top1s with point mutations that confer resistance to camptothecin, suggesting the effect of an endogenous toxic metabolite on the evolution of the target cellular component
-
-
brenda
E233, spontaneous uracil-auxotrophic mutant derived from Sulfolobus islandicus Rey15A
SwissProt
brenda
E233, spontaneous uracil-auxotrophic mutant derived from Sulfolobus islandicus Rey15A
SwissProt
brenda
-
3795, 3801, 3811, 3813, 3817, 3819, 3836, 3839, 3844, 3845, 3850, 3851, 649339, 649539, 649691, 649801, 650642, 650940, 651764, 652052, 652732, 653140, 653375, 654011, 661327, 661352
-
-
brenda
-
691137, 691221, 691264, 691321, 691568, 691582, 691608, 691619, 691728, 691729, 692246, 692660, 692707, 693067, 693113, 693400, 693401, 693543
-
-
brenda
-
714330, 714448, 714463, 714474, 714643, 714760, 714814, 714900, 714903, 715867, 716007, 716380, 726976, 727170, 727417, 728098, 728293, 728558, 728560, 728579, 728639, 728804
-
-
brenda
multiple forms of mitochondrial topoisomerase I: 66000 MW form, 77000 ME form and 100000 MW form
-
-
brenda
-
-
-
brenda
yeast TOP1 null strain, JEL1delta top1, strain BY4741, strain YOL006C-TAP
-
-
brenda
topoisomerase I, TopA, is the only topoisomerase I homologue in the organism
-
-
brenda
-
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
Caco-2 cells have eight copies of the hTOPI gene, they show twofold more hTopI protein, and twofold higher activity of hTopI compared to HT-29 cells, but similar camptothecin sensitivity
brenda
-
level of topo I increases from birth to maturity and decreases, more significantly in males, with senescence
brenda
-
from patients receiving adjuvant 5-fluorouracil-based chemotherapy
brenda
-
a cisplatin resistant subline of the KF epithelial ovarian carcinoma cell line
brenda
additional information
-
from patients receiving adjuvant 5-fluorouracil-based chemotherapy
brenda
-
-
brenda
-
HT-29 cells have five copies of the hTOPI gene, they show twofold less hTopI protein, and twofold lower activity of hTopI compared to Caco-2 cells, but similar camptothecin sensitivity
brenda
-
topoisomerase I activity is not significantly changed as a function of regeneration time after partial hepatectomy
brenda
-
-
brenda
additional information
each inhibitor compound is evaluated against approximately 60 cell lines originating from various human tumors
brenda
additional information
-
the enzyme is often upregulated in cancer cells and overexpressed in a wide range of cancers
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
LdTopIIIbeta protein localized both inside the nucleus and kinetoplast of the parasites
brenda
-
LdTopIIIbeta protein localized both inside the nucleus and kinetoplast of the parasites
-
brenda
-
isozymes Top1mt, Top3alpha and a truncated form of Top2beta
brenda
-
-
3795, 3819, 702176, 702579, 702598, 702602, 702620, 702689, 702885, 705047, 714463, 714760, 714814, 714900, 714903, 716007, 728293, 747693, 748187, 750368
brenda
LdTopIIIbeta protein localized both inside the nucleus and kinetoplast of the parasites
brenda
-
LdTopIIIbeta protein localized both inside the nucleus and kinetoplast of the parasites
-
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
genes encoding topoisomerase III enzymes are highly conserved in evolution from bacteria to human
evolution
-
activity comparison of two related type IA topoisomerases, Topo I and Topo III: Topo I initiates relaxation sooner than Topo III. and for most substrates, the pauses between relaxation runs catalyzed by Topo I are spaced by only a few seconds, whereas Topo III paused for tens of seconds in between relaxation runs
evolution
-
Escherichia coli topoisomerase I belongs to type I subfamily DNA topoisomerases. YrdD, a homolog of the C-terminal zinc binding region of Escherichia coli topoisomerase I, is highly conserved among proteobacteria and enterobacteria
evolution
-
type IA enzymes are ubiquitous. They are present in bacteria, archaea and eukarya. Although all type IA topoisomerases are related at the sequence, structure and mechanism levels, different type IA enzymes do not participate in the same cellular processes. For topoisomerase I in DNA relaxation reaction, the pauses are short and the relaxation runs are slow, while topoisomerase III behaves the opposite way: the the pauses are long and the relaxation runs are fast. The combination of these two general features results in topoisomerase I having a higher overall relaxation rate than topoisomerase III
evolution
-
genes encoding topoisomerase III enzymes are highly conserved in evolution from bacteria to human
-
malfunction
-
eukaryotic top1 is affected by the modification of DNA by antitumor cisplatin
malfunction
-
selective inhibition of Cdc2-like kinases and DNA topoisomerase I elicite distinct changes in TF biosynthesis in TNF-alpha-stimulated endothelial cells, which impact endothelial procoagulant activity, overview
malfunction
-
Top1-deficient cells accumulate stalled replication forks and chromosome breaks in S phase resulting in supercoiled DNA and altered RNA splicing, breaks occur preferentially at gene-rich regions of the genome
malfunction
-
accumulation of cleavage complex formed by inactivated MtTOP1 is lethal for the cell
malfunction
-
enzyme inhibition activates transcriptional Cdk (Cdk9 and/or Cdk7) activity leading o the hyperphosphorylation of the CTD of the largest subunit of RNA polymerase II
malfunction
the phenotypic consequences of loss of topoisomerase III function are generally quite severe
malfunction
-
mitochondria are dysfunctional in mitochondrial isozyme Top1mt-deficient cells, the ATP content is 2fold less in Top1mt-/- compared to wild-type cells, confirming dysfunctional respiratory chain in Top1mt-/- cells. The mutant cells also show Increases of fatty acid oxidation and lipogenesis. Isozyme Top1mt deficiency leads to increased glycolytic activity
malfunction
-
the enzyme depletion inhibits growth, blocks sporulation, and affects septation and chromosome condensation. But sporulation in the TopA-depleted strain can be partially restored by deletion of parB. Depletion of the TopA protein affects the secondary metabolism of Streptomyces coelicolor, leading to overproduction of actinorhodin
malfunction
-
TOP1 mutations are involved in the development of SN38 resistance. Mutation of one of residues L617, R621, and E710, important for the functionality of the linker, is sufficient to alter or modulate its flexibility. DNA double strand break formation is reduced in SN38 resistant HCT116 cells. Colorectal cancer patients and SN38 resistant HCT116 clones phemotypes, overview
malfunction
topA deletion mutant strain DELTAtopA grows more slowly than the wild-type strain. The doubling time of the mutant is 11.9 h, as compared to 7.4 h for the wild-type strain, when both strains are grown in the rich medium at 75°C. The enzyme may not serve a critical role in the adaptation of thermophilic archaea to growth at high temperature
malfunction
-
the phenotypic consequences of loss of topoisomerase III function are generally quite severe
-
malfunction
-
topA deletion mutant strain DELTAtopA grows more slowly than the wild-type strain. The doubling time of the mutant is 11.9 h, as compared to 7.4 h for the wild-type strain, when both strains are grown in the rich medium at 75°C. The enzyme may not serve a critical role in the adaptation of thermophilic archaea to growth at high temperature
-
metabolism
-
the mycobacterial topoisomerase I physically interacts with its ribokinase both in vitro and in vivo with opposite effects on their respective function, overview. While the interaction between the two proteins inhibits the ability of TopA to relax supercoiled DNA, it stimulates ribokinase activity as a regulatory strategy for efficient utilization of D-ribose
metabolism
the mycobacterial topoisomerase I physically interacts with its ribokinase both in vitro and in vivo with opposite effects on their respective function, overview. While the interaction between the two proteins inhibits the ability of TopA to relax supercoiled DNA, it stimulates ribokinase activity as a regulatory strategy for efficient utilization of D-ribose
metabolism
-
the mycobacterial topoisomerase I physically interacts with its ribokinase both in vitro and in vivo with opposite effects on their respective function, overview. While the interaction between the two proteins inhibits the ability of TopA to relax supercoiled DNA, it stimulates ribokinase activity as a regulatory strategy for efficient utilization of D-ribose
-
physiological function
-
Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue factor, TF,via phosphorylation of serine/arginine-rich proteins
physiological function
-
DNA topoisomerase enzymes regulate the topological state of DNA that is crucial for initiation and elongation during DNA synthesis
physiological function
-
DNA topoisomerase I is ubiquitous and essential in mammals and is involved in tumor growth
physiological function
-
the enzyme is of fundamental importance to processes such as replication, recombination and transcription
physiological function
-
topoisomerase I but not thymidylate synthase is associated with improved outcome in patients with resected colorectal cancer treated with irinotecan containing adjuvant chemotherapy, Topo I expression is associated with a reduced risk of death, overview
physiological function
-
topoisomerase I is a key enzyme in functioning at the interface between DNA replication, transcription and mRNA maturation. Top1 suppresses genomic instability in mammalian cells by preventing a conflict between transcription and DNA replication, it prevents replication fork collapse by suppressing the formation of R-loops in an ASF/SF2-dependent manner
physiological function
-
as a result of its catalytic mechanism, topoisomerase I plays an important role in removing positive DNA supercoils that accumulate ahead of replication forks and transcription complexes. Cleavage events most likely to generate permanent genomic damage are those that occur ahead of DNA tracking systems. The human enzyme maintains higher levels of cleavage with positively as opposed to negatively supercoiled substrates in the absence or presence of anticancer drugs. Sites of topoisomerase I-mediated DNA cleavage do not appear to be affected by supercoil geometry, but rates of ligation are slower with positively supercoiled substrates
physiological function
-
bacterial topoisomerase I plays a major role in preventing excessive negative supercoiling of DNA and its function is actively involved in the SOS response to antibiotics and stress challenge. Cell killing initiated by the topoisomerase I cleavage complex is enhanced by antibiotics and the host response. During rapid transcription at gene loci induced by the stress response, movement of the RNA polymerase complex leads to increased negative supercoiling behind the complex. Topoisomerase I is needed to prevent hypernegative supercoiling and R-loop formation, which would otherwise inhibit the expression of the stress response genes. Topoisomerase I function is required for efficient transcriptional activation of the recA and dinD1 promoters during the Escherichia coli SOS response to trimethoprim and mitomycin C
physiological function
-
c-myc is a key regulator for nuclear-encoded mitochondrial genes including mitochondrial isozyme TOP1mt
physiological function
-
human topoisomerase I shows transient nicking of double-stranded DNA. Because of this activity, topo I is a main nuclear swivelase responsible for relieving a torsional stress that appears in DNA during transcription, replication, and chromatin condensation. The activity is also used to remove ribonucleotides incorporated during DNA replication and not deleted by the repair system. Because of the kinase activity of topo I, it influences alternative splicing of several transcripts. Both DNA relaxation and phosphorylation activities of topo I are also cooperating in preventing a conflict between transcription and DNA replication. Both activities do not work at the same time: DNA, a substrate for DNA relaxation, inhibits the kinase reaction, whereas both a protein substrate for the kinase activity and ATP inhibit DNA nicking
physiological function
-
reverse gyrase is a DNA topoisomerase, specific to microorganisms living at high temperatures, which comprises a type IA topoisomerase fused to an SF2 helicase-like module and catalyzes ATP hydrolysis-dependent DNA positive supercoiling. Reverse gyrase is likely involved in regulation of DNA structure and stability and might also participate in the cell response to DNA damage
physiological function
-
topoisomerase I is recruited to ParB complexes and is required for proper chromosome organization during Streptomyces coelicolor sporulation, overview
physiological function
-
topoisomerase I relaxes supercoiled DNA during cell division
physiological function
-
topoisomerases are the enzymes responsible for maintaining the supercoiled state of DNA in the cell and also for many other DNA-topology-associated reactions. Type IA enzymes alter DNA topology by breaking one DNA strand and passing another strand or strands through the break
physiological function
-
DANN topoisomerase I is a critical DNA-nicking enzyme involved in the process of cell-specific, ligand-driven enhancer activation. The enzyme occupies androgen receptor-enhancers KLK3 and KLK2 and affects the transcriptional program of the prostate cancer cell line LNCaP
physiological function
the enzyme is required for the termination of floral stem cell maintenance and is required for the repression of WUS expression in flower development. The enzyme decreases nucleosome density which probably allows the binding of factors that either recruit polycomb group proteins or counteract polycomb group-mediated regulation
physiological function
-
the enzyme is required for stem cell regulation in shoot and floral meristems as well as adaptive response to light and flower development
physiological function
-
the enzyme modulates the replication process via R-loop formation
physiological function
-
reverse gyrase is a DNA topoisomerase, specific to microorganisms living at high temperatures, which comprises a type IA topoisomerase fused to an SF2 helicase-like module and catalyzes ATP hydrolysis-dependent DNA positive supercoiling. Reverse gyrase is likely involved in regulation of DNA structure and stability and might also participate in the cell response to DNA damage
-
physiological function
-
bacterial topoisomerase I plays a major role in preventing excessive negative supercoiling of DNA and its function is actively involved in the SOS response to antibiotics and stress challenge. Cell killing initiated by the topoisomerase I cleavage complex is enhanced by antibiotics and the host response. During rapid transcription at gene loci induced by the stress response, movement of the RNA polymerase complex leads to increased negative supercoiling behind the complex. Topoisomerase I is needed to prevent hypernegative supercoiling and R-loop formation, which would otherwise inhibit the expression of the stress response genes. Topoisomerase I function is required for efficient transcriptional activation of the recA and dinD1 promoters during the Escherichia coli SOS response to trimethoprim and mitomycin C
-
additional information
-
camptothecin is a selective inhibitor of DNA topoisomerase I. Camptothecin activates the transcription of low-abundance antisense RNAs at the HIF-1alpha gene locus in human cancer cells in a Topoisomerase I-dependent manner, likely due to sustained drug interference with transcription regulation mechanisms leading to a more open chromatin conformation and de-repression/activation of antisense transcription
additional information
-
enzyme model showing that the second site capture might account for DNA crossover binding, nucleation of DNA synapsis, and plectonemic supercoiling within the synaptic filament in TopIB enzyme with both DNA sites filled, overview
additional information
-
inhibition of topoisomerase I prevents chromosome breakage at common fragile sites. Polymerase-helicase uncoupling is a key initial event in this process
additional information
-
intercalators enhance topoisomerase I-mediated cleavage of negatively supercoiled substrates but not positively supercoiled or linear DNA. These compounds act by altering the perceived topological state of the double helix, making underwound DNA appear to be overwound to the enzyme, acting like topological poisons of topoisomerase I
additional information
LdTopIIIbeta suppresses the yeast top3DELTA slow-growth phenotype. The C-terminal domain of LdTopIIIbeta is essential for in vivo complementation
additional information
-
LdTopIIIbeta suppresses the yeast top3DELTA slow-growth phenotype. The C-terminal domain of LdTopIIIbeta is essential for in vivo complementation
additional information
-
many antibacterial and anticancer drugs initiate cell killing by trapping the covalent complexes formed by topoisomerases
additional information
-
the enzyme-DNA covalent adduct is recombinogenic in cells, because the nicked strand downstream of the cleavage site can dissociate and be replaced by another DNA strand, potentially resulting in genome rearrangements if the enzyme executes strand ligation. The enzyme plays an active role in strand exchange, either by altering the kinetics or thermodynamics of DNA strand binding, or by serving as a proofreading gate to prevent ligation of incoming DNA strands containing mismatches. Topo I-mediated strand exchange can be divided into two distinct steps: (1) a strand binding step, which involves replacement of the nicked, base paired DNA strand with a new incoming strand, and (2) a strand ligation step, which results in covalent attachment of the new DNA strand at the vTopo cleavage site. Oscillation between an open and closed state of the covalently bound enzyme is likely important for regulating the number of DNA superhelical turns that are removed during the lifetime of the covalent complex with supercoiled substrates. vTopo also resolves pre-formed Holliday junctions that contain the consensus cleavage sequence, and when recombinantly expressed in Escherichia coli, promotes illegitimate recombination
additional information
-
the TOPRIM motif DxDxxG is strictly conserved in type IA topoisomerase sequences and plays an essential role for divalent ion coordination and cleavage-religation of DNA during catalysis
additional information
-
induction of mutant YpTOP1-D117N topoisomerase I in Escherichia coli strain BW117N with 0.002%-0.02% arabinose results in a 104-105fold decrease in viability due to the lethal stabilized covalent complex
additional information
-
residues L617, R621, and E710 are important for the functionality of the linker in the enzyme
additional information
-
residues R169, R173 and Y177 work together to interact with a cytosine base at the -4 position to facilitate DNA cleavage. R169 and R173 interact with the cytosine base at the -4 position via hydrogen bonds while the phenol ring of Y177 wedges between the bases at the -4 and the -5 position
additional information
-
structure-function-relationship, overview. Topo I is one of several protein kinases that phosphorylate SR proteins, enzymes of both families, SRPK1 and CLK1. SRPK1 efficiently phosphorylates serine residues localized in the N-terminal fragment of RS in SRSF1,23,24 while CLK1 phosphorylates all serine residues in RS25 or serine residues in the C-terminal portion of RS in SRSF1 previously phosphorylated by SRPK1. Topoisomerase I interacts with kinase SRSF1, interaction analysis with wild-type and mutant Topo I and wild-type and mutant SrSF1 kinase, phosphorylation sites, modeling, overview. Interactions between N-terminal domain and other domains of topo I are different for the protein in a complex with either DNA or SRSF1
additional information
-
the C-terminal domain contains three basic stretches that are essential for the DNA relaxation activity. The basic amino acid stretches confer the non-specific DNA-binding property to the C-terminal domain, overview
additional information
-
TopA contains an N-terminal catalytic fragment and a C-terminal zinc-binding region that is required for relaxation of the negatively supercoiled DNA
additional information
-
YrdD is a homologue of the C-terminal zinc binding region of Escherichia coli topoisomerase I. The enzyme contains an N-terminal catalytic fragment and a C-terminal zinc binding region. While the N-terminal fragment is sufficient for cleaving single-stranded DNA, the C-terminal region is required for relaxing the negatively supercoiled DNA and for interacting with RNA polymerase
additional information
-
LdTopIIIbeta suppresses the yeast top3DELTA slow-growth phenotype. The C-terminal domain of LdTopIIIbeta is essential for in vivo complementation
-
additional information
-
induction of mutant YpTOP1-D117N topoisomerase I in Escherichia coli strain BW117N with 0.002%-0.02% arabinose results in a 104-105fold decrease in viability due to the lethal stabilized covalent complex
-
Show AA Sequence and Transmembrane Helices (82460 entries)
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
100000
102000
110000
145000
-
gel filtration, glycerol density gradient centrifugation, weakly associated dimer exists at high ionic strength
150000
-
4 forms of DNA topoisomerase I with MW 80000, MW 100000, MW 110000, and MW 150000, PAGE, gel filtration
28000
29000
30000
32000
33000
36000
-
x * 90000 + x * 36000, the large subunit contains the DNA-binding domain, the small subunit contains the catalytic domain, each subunit is essential for trypanosome survival
63000
-
1 * 63000, SDS-PAGE. The purified 63000 MW protein is a proteolytic fragment of a protein with a molecular mass of 100000
64000
-
gel filtration, glycerol density gradient centrifugation, monomeric form exists at low ionic strength
65000
70000
73000
79000
80000
90000
91000
97000
98000
additional information
100000
-
4 forms of DNA topoisomerase I with MW 80000, MW 100000, MW 110000, and MW 150000, PAGE, gel filtration
102000
-
Leishmania bisubunit topoisomerase I fusion construct, LdTOPIL and LdTOPIS and the deduced amino acid sequences of the fusion regions
102000
-
point mutations generate at the His453 position of the LdTOPIL-fus-S gene to H453A and H453Q
102000
-
reverse fusion construct of Leishmania bisubunit topoisomerase I, LdTOPIS and LdTOPIL and the deduced amino acid sequences of the fusion regions
102000
-
1 * 102000, enzyme form p102, SDS-PAGE. The two enzyme forms P98 and p102 are structurally related
110000
-
4 forms of DNA topoisomerase I with MW 80000, MW 100000, MW 110000, and MW 150000, PAGE, gel filtration
28000
-
small subunit LdTOPIB, on chromosome 4, encoding for a 262-amino acid polypeptide. The small subunit contains SKXXY motif placed at the C-terminal domain of all type I DNA topoisomerases, which conserves the tyrosine residue that plays a role in DNA cleavage
29000
-
1 * 29000 + 1 * 73000, LdTOP1L (large subunit) and LdTOP1S (small subunit) form a direct 1:1 heterodimer complex through protein-protein interaction, SDS-PAGE
30000
-
x * 30000, SDS-PAGE, may exist as a multimeric protein in the native state
32000
-
poxviridae topoisomerase smallest known topoisomerase, maintains higher levels of covalent enzyme-cleaved DNA intermediates during its catalytic cycle than the eukaryotic type IB enzyme. Poxviridae topoisomerase is refractory to the drug camptothecin. Poxviridae topoisomerase IB is highly sequence specific. Crystal structure of the non-covalent variola topoisomerase IBDNA complex and that of the covalent enzymeDNA cleavage complex are known. These structures provide an explanation for some of the unique features of Poxviridae topoisomerase IB. Crystal structures of the variola and human topoisomerase IB-DNA cleavage complexes compared
73000
-
full-length larger subunit as the core DNA-binding subunit with the conserved catalytic His at position 453
73000
-
large subunit LdTOPIA, on chromosome 34, encoding for a 636-amino acid polypeptide
73000
-
1 * 29000 + 1 * 73000, LdTOP1L (large subunit) and LdTOP1S (small subunit) form a direct 1:1 heterodimer complex through protein-protein interaction, SDS-PAGE
79000
-
N-terminal truncated small subunit (amino acids 211262) fuse to intact large subunit to generate an ORF, LdTOPIL-fus-D(1210)S
80000
-
gel filtration, the purified protein represents a proteolytic fragment of a larger protein
80000
-
4 forms of DNA topoisomerase I with MW 80000, MW 100000, MW 110000, and MW 150000, PAGE, gel filtration
90000
-
x * 90000 + x * 36000, the large subunit contains the DNA-binding domain, the small subunit contains the catalytic domain, each subunit is essential for trypanosome survival
98000
-
1 * 98000, enzyme form p98, SDS-PAGE. The two enzyme form P98 and p102 are structurally related
additional information
-
large subunit (LdTop1L), which contains the non-conserved N-terminal end and a phylogenetically conserved core domain, and of a small subunit (LdTop1S) which harbours the C-terminal region with a characteristic tyrosine residue in the active site
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
heterodimer
heterotetramer
-
silver staining, Western blotting, cross-linking of topo IV with glutaraldehyde in the absence of DNA. Southern blotting, cross-linking of Topo IV in the presence of DNA, composed of two molecules each of ParC and ParE, topo IV binds the gate segment and the transport segment of DNA. The Par E subunit dimerize prior to strand passage
monomer
additional information
?
-
peptides with topoisomerase I activity detected by SDS-PAGE: 105000 MW, 83000 MW, 54000 MW and 30000 MW
?
-
x * 30000, SDS-PAGE, may exist as a multimeric protein in the native state
?
-
proteins with MW 75000, 83000, 91000 or 100000 with DNA topoisomerase I activity are detected
?
-
x * 90000 + x * 36000, the large subunit contains the DNA-binding domain, the small subunit contains the catalytic domain, each subunit is essential for trypanosome survival
dimer
-
2 * 100000, SDS-PAGE. DNA topoisomerase I exists largely in a monomeric form, but also has a minor population of the dimeric form
dimer
-
1 * 29000 + 1 * 73000, LdTOP1L (large subunit) and LdTOP1S (small subunit) form a direct 1:1 heterodimer complex through protein-protein interaction, SDS-PAGE
heterodimer
-
DNA topoisomerase I of kinetoplastid protozoan parasite Leishmania donovani is an unusual bi-subunit enzyme. To find out the differential affinity of 3,3-diindolylmethane towards the large subunit (LdTOP1L) and small subunit (LdTOP1S) of Leishmania donovani topoisomerase I, performed the binding of individual subunits with 3,3-diindolylmethane by equilibrium dialysis experiment
heterodimer
-
Leishmania donovani topoisomerase I is an unusual bi-subunit enzyme where the core DNA binding domain and the catalytic domain harboring the consensus SKXXY motif lie in separate subunits. The two subunits (LdTOP1L and LdTOP1S) are synthesized by two different genes, which associate with each other through proteinprotein interaction to form an active heterodimeric topoisomerase I within the parasite
heterodimer
-
the genes encoding each protein subunit are located on different chromosomes
heterodimer
-
unique heterodimeric DNA topoisomerase IB, consists of a large subunit (LdTop1L), which contains the non-conserved N-terminal end and a phylogenetically conserved core domain, and of a small subunit (LdTop1S) which harbours the C-terminal region with a characteristic tyrosine residue in the active site
heterodimer
-
large subunit (LdTOPIL or L) and the catalytic small subunit (LdTOPIS or S)
heterodimer
-
presence of two separate genes encoding for the core and catalytic domains, indicating that this singular feature is common to all trypanosomatids
monomer
-
The sedimentation results are consistent with MimiTopIB being a monomer in solution, although the prospect that MimiTopIB is an asymmetrically shaped homodimer cannot excluded
monomer
-
1 * 63000, SDS-PAGE. The purified 63000 MW protein is a proteolytic fragment of a protein with a molecular mass of 100000
monomer
-
1 * 108000, electrophoresis under denaturing conditions
monomer
-
1 * 108000, electrophoresis under denaturing conditions
-
monomer
-
1 * 100000, SDS-PAGE. DNA topoisomerase I exists largely in a monomeric form, but also has a minor population of the dimeric form
monomer
-
765 amino acids. All type IB topoisomerases contain a conserved SKXXY signature in the region in which a tyrosine residue (Tyr-723 in the human topoisomeraseI) is the DNA-cleaving amino acid
monomer
-
usually works as a monomer, previously shown that two molecules can form a dimer-like protein-protein complex on a suicide DNA substrate resulting in a topoisomerase I double cleavage complex. Here human topoisomerase I forms a transient dimer. Probably human topoisomerase I double cleavage complexes are part of the normal catalytic cycle of this enzyme that occur in vitro and possibly also in vivo
monomer
-
the kinetoplastid family (Trypanosoma and Leishmania) possess an unusual bisubunit topoisomerase I. In vitro gene fusion of Leishmania bisubunit topoisomerase I into a single ORF encoding a new monomeric topoisomerase I (LdTOPIL-fus-S). This unusual structure of DNA topoisomerase I may provide a missing link in the evolution of type IB enzymes. LdTOPIL-fus-S fusion protein is a functional topoisomerase I. DNA-binding assays shown
monomer
-
765 amino acids. All type IB topoisomerases contain a conserved SKXXY signature in the regionin which a tyrosine residue is the DNA-cleaving amino acid
monomer
-
1 * 98000, enzyme form p98, SDS-PAGE. The two enzyme form P98 and p102 are structurally related
monomer
-
1 * 102000, enzyme form p102, SDS-PAGE. The two enzyme forms P98 and p102 are structurally related
monomer
-
Three structural domains, N-terminus domain (134 amino acids) poorly conserved, a 500 amino acid length block of conserved amino acids with high homology to the core domain of the human protein, the C-terminal domain is smaller than the hosts' but conserves the active tyrosine at position 798 which makes the enzyme fully active
additional information
-
the DraTopIB 139GSDIYARQHK148 peptide forms a well-ordered alpha-helix that mimics the specificity helix of poxvirus TopIB, comparison of structures of DraTopIB and poxvirus TopIB, overview. Several mechanisms might exist to trigger the folding of the specificity heli
additional information
-
other cross-linking reagents than glutaraldehyde tested. Western blot analysis of cross-linked topo IV bound to DNA. Model for topo IV tetramers bound to (-)- and (+)-SC DNA shown
additional information
-
the enzyme structure with bound DNA shows distinct conformational changes from the structure of the enzyme without bound DNA, overview. The portion of cleaved DNA 5' to the site of cleavage is anchored tightly with extensive noncovalent protein-DNA interactions. The portion of the oligonucleotide 5' to the cleavage site binds in a deep groove formed at the interface of domains I and III as well as within domain IV, in a similar orientation. Structure comparison of wild-type and D111N mutant enzymes, overview
additional information
-
the enzyme contains an N-terminal catalytic fragment of 67 kDa and a C-terminal zinc binding region of 30 kDa
additional information
-
TopA contains an N-terminal catalytic fragment and a C-terminal zinc-binding region that is required for relaxation of the negatively supercoiled DNA
additional information
-
relaxation activity of human TopI by adding to the core domain a series of peptides containing the C-terminal domain in the presence of DNA. Reinforced by using a two-hybrid expression system, identified proteins containing part of the linker and the C-terminal domain that supplemented the catalytic core of Saccharomyces cerevisiae topoisomerase I
additional information
structure-function relationship, molecular dynamics modelling, detailed overview. Topo I is a single polypeptide of 765 amino acid residues comprising four domains called: N-terminal domain with residues M1-G214, core domain with I215-A635, linker domain with P636-K712, and C-terminal domain with Q713-F765 domain. The core domain is further divided into three subdomains that form two distinct lobes in the three-dimensional structure of topo I: the cap region, including subdomains I formed by residues I215-E232 and S320-S433, subdomain II formed by residues P233-M319, and the separate subdomain III consisting of residues R434-A635
additional information
-
structure-function relationship, molecular dynamics modelling, detailed overview. Topo I is a single polypeptide of 765 amino acid residues comprising four domains called: N-terminal domain with residues M1-G214, core domain with I215-A635, linker domain with P636-K712, and C-terminal domain with Q713-F765 domain. The core domain is further divided into three subdomains that form two distinct lobes in the three-dimensional structure of topo I: the cap region, including subdomains I formed by residues I215-E232 and S320-S433, subdomain II formed by residues P233-M319, and the separate subdomain III consisting of residues R434-A635
additional information
-
Topo I is a single polypeptide of 765 amino acid residues composed of four domains: N-terminal domain (residues 1-214), core domain (residues 215-635), linker domain (residues 636-712), and C-terminal domain (residues 713-765). The core domain is further divided into three subdomains that form two distinct lobes in the threedimensional structure of topo I: the cap, including subdomains I and II (residues 215-433), and subdomain III (residues 434-635). Interactions between N-terminal domain and other domains of topo I are different for the protein in a complex with either DNA or SRSF1
additional information
-
important role by part of the N-terminal extension of the small subunit of DNA topoisomerase I, contribute with a main portion of the linker domain of this enzyme
additional information
three-dimensional ribbon structure of LdTopIIIbeta generated based on the crystal structure of Escherichia coli topo isomerase III, overview
additional information
-
three-dimensional ribbon structure of LdTopIIIbeta generated based on the crystal structure of Escherichia coli topo isomerase III, overview
additional information
-
three-dimensional ribbon structure of LdTopIIIbeta generated based on the crystal structure of Escherichia coli topo isomerase III, overview
-
additional information
-
structure-function analysis of MtTOP1, overview
additional information
-
regulation of DNA topoisomerase I, different expression patterns described in the distinct life cycle stages of Plasmodium falciparum. An indirect evidence of potential post-translational mechanisms which could operate on Plasmodium topoisomerases at different stages of its life cycle
additional information
domain mapping analysis shows that the enzyme is composed of conserved four domains, I through IV, together with a variable C-terminal region containing a unique domain V
additional information
-
domain mapping analysis shows that the enzyme is composed of conserved four domains, I through IV, together with a variable C-terminal region containing a unique domain V
additional information
-
domain mapping analysis shows that the enzyme is composed of conserved four domains, I through IV, together with a variable C-terminal region containing a unique domain V
-
additional information
multimeric status of Trypanosoma brucei TopI. Molecular mass determination by gel filtration chromatography suggests that the native enzyme might exist as a tetrameric active A2B2 form or two heterodimers would facilitate the binding at the helical crossover points of DNA
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
-
phorsphorylation by Top1 kinase29 is required for activity, inhibition o by diospyrin induces a 10fold increase in DNA breaks in Top1-proficient cells
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified DraTopIB enzyme in a complex with 12-bp duplex DNA, hanging drop vapor diffusion method, from 30% PEG 400 w/v, 0.1 M sodium acetate, pH 4.5, 0.2 M calcium chloride, X-ray diffraction structure determination and analysis, molecular replacement
-
D111N mutant topoisomerase I catalytic domain, residues 2-695, in covalent complex with a cleaved single-stranded oligonucleotide substrate, X-ray diffraction structure determination and analysis at 2.3 A resolution
-
expressed in Escherichia coli BL21 cells and purified. Wild type enzyme+ssDNA complex crystallize under the same conditions that produce crystals of the Escherichia coli topoisomerase III (Y328F)+ssDNA complex. The new crystals grow in a different crystal form. In the new crystals, there are two molecules in the asymmetric unit almost related by a 2-fold axis
hanging drop method, crystal structure at 2.05 A resolution, of an inactive mutant of topoisomerase III in a noncovalent complex with an 8-base ssDNA molecule
-
hanging-drop vapor-diffusion method, complex between DNA topoisomerase I and single-stranded DNA
-
hanging-drop vapor-diffusion method, fragment of the enzyme comprising residues 214-477
crystal structures of two camptothecin-resistant forms of human topoisomerase I F361S at 2.6 A resolution and N722S at 2.3 A resolution. Cell dimensions for N722S are: a = 57.3 A, b = 116.3 A, c = 75.2 A, beta = 94.3°, space group P2(1). Cell dimensions for F361S are: a = 57.6 A, b = 115.6 A, c = 75.0 A, beta = 96.3 A
topo70 K532R/Y723F protein in complex with a 22-mer duplex DNA oligonucleotide, vapour diffusion at room. Cell dimensions: a = 56.9 A, b = 118.6 A, c = 71.7 A, beta = 98.3°
sitting drop vapor diffusion method, using 0.2 M ammonium sulfate, 0.1 M Tris-HCl pH 8.5, and 25% (w/v) PEG3350
-
crystallization experiments are performed at 18°C using hanging-drop vapour diffusion method with O-(2-aminopropyl)-O'-(2-methoxyethyl)polypropylene glycol 500 as precipitant. Crystal structure of the full length enzyme is determined at 1.7 A resolution
crystal structure of the non-covalent variola topoisomerase IBDNA complex and that of the covalent enzymeDNA cleavage complex are known. These structures provide an explanation for some of the unique features of Poxviridae topoisomerase IB. Crystal structures of the variola and human topoisomerase IB-DNA cleavage complexes compared
-
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H285A
-
display a low level of supercoil relaxation. Slow the rate of cleavage by a factor of 60 compared to the wild-type
R135A
-
form no detectable protein-DNA adduct during a 24 h incubation with the suicide substrate. The failure of this protein to relax supercoiled DNA is probably attributable to its inability to perform transesterification chemistry
R241A
-
form no detectable protein-DNA adduct during a 24 h incubation with the suicide substrate. The failure of this protein to relax supercoiled DNA is probably attributable to its inability to perform transesterification chemistry
Y294A
-
form no detectable protein-DNA adduct during a 24 h incubation with the suicide substrate. The failure of this protein to relax supercoiled DNA is probably attributable to its inability to perform transesterification chemistry
D111N
D117N
-
site-directed mutagenesis, induction of mutant YpTOP1-D117N topoisomerase by arabinose is similar in the absence or presence of trimethoprim
G194A
-
40fold reduction in relaxation activity when compared to wild-type enzyme, DNA cleavage activity is 100fold lower than that of the wild-type enzyme
H365A
-
whereas wild type enzyme shows pH-dependent cleavage of oligonucleotides, cleavage by the mutant enzyme is pH-independent. Cleaves DNA with a slower rate than the wild-type enzyme, but can cleave more substrate overall, mutant enzyme has a lower DNA binding affinity than the wild-type enzyme, mutant shows a shift in maximal relaxation to above pH 8.5, mutant enzyme is less able than the wild type enzyme to relax negatively supercoiled DNA
H365D |
-
mutant shows a shift in maximal relaxation to above pH 8.5, mutant enzyme is less able than the wild type enzyme to relax negatively supercoiled DNA
H365E |
-
mutant shows a shift in maximal relaxation to above pH 8.5, mutant enzyme is less able than the wild type enzyme to relax negatively supercoiled DNA
H365N
-
mutant shows a shift in maximal relaxation to above pH 8.5, mutant enzyme is less able than the wild type enzyme to relax negatively supercoiled DNA
H365Q
-
whereas wild type enzyme shows pH-dependent cleavage of oligonucleotides, cleavage by the mutant enzyme is pH-independent. Cleaves DNA with rates similar to the wild-type enzyme, mutant shows a shift in maximal relaxation to above pH 8.5, mutant enzyme is less able than the wild type enzyme to relax negatively supercoiled DNA
H365R |
-
mutant shows a shift in maximal relaxation to above pH 8.5, mutant enzyme is less able than the wild type enzyme to relax negatively supercoiled DNA
K13A
-
Investigation of the potential catalytic role of the serine and lysine residue conserved in the active site region of bacterial topoisomerase I Ser10 and Lys13 of Escherichia coli DNA topoisomerase I are mutated to alanines. 50-to 100fold reduction in relaxation activity, not affected in non-covalent DNA binding, mutations at Ser10 and Lys13 highly reduce the ability of topoisomerase I to support growth of the Escherichia coli cells, as expected from the loss of the relaxation activity. Ala13 is unable to make interactions with the acidic residues of the active site. Side chains of Ser10 and Lys13 are required for DNA cleavage activity, rates of cleavage are too low to be analyzed
K13R
-
Arg13 residue is a larger residue than lysine, and is unable to fit in the space assigned to Lys13. Reduced DNA binding affinity, possibly changing Ser10 to a threonine residue, and changing Lys13 to arginine allow retention of activity, relaxation activity assays show that introduction of a different side chain with similar functionality but different steric properties at these two positions result in even lower relaxation activitymutations at Ser10 and Lys13 highly reduce the ability of topoisomerase I to support growth of the Escherichia coli cells, as expected from the loss of the relaxation activity. Do not have severe changes in protein folding. Side chains of Ser10 and Lys13 are required for DNA cleavage activity, rates of cleavage are too low to be analyzed
R169
-
site-directed mutagenesis, the mutant shows reduced DNA cleavage and relaxation activity compared to the wild-type enzyme, the mutation to alanine changesd the selectivity of the enzyme for the base at the -4 position from a cytosine to an adenine
R173A
-
site-directed mutagenesis, the mutant displays similar sequence selectivity as the wild-type enzyme, but weaker cleavage and relaxation activity
R321F
-
site-directed mutagenesis, constants of oligonucleotide binding compared to the wild-type enzyme, the mutant shows reduced DNA cleavage and requirement for Mg2+
R321K
-
site-directed mutagenesis, constants of oligonucleotide binding compared to the wild-type enzyme, the mutant shows reduced DNA cleavage and requirement for Mg2+
R321L
-
site-directed mutagenesis, constants of oligonucleotide binding compared to the wild-type enzyme, the mutant shows reduced DNA cleavage and requirement for Mg2+
S10A
-
Investigation of the potential catalytic role of the serine and lysine residue conserved in the active site region of bacterial topoisomerase I Ser10 and Lys13 of Escherichia coli DNA topoisomerase I are mutated to alanines. 5-to 10fold reduction in relaxation activity, not affected in non-covalent DNA binding, mutations at Ser10 and Lys13 highly reduce the ability of topoisomerase I to support growth of the Escherichia coli cells, as expected from the loss of the relaxation activity. Ala10 is unable to form a hydrogen bond with phosphate 8. Side chains of Ser10 and Lys13 are required for DNA cleavage activity, yield of the cleaved complex observed is 30fold lower than the wild-type enzyme at each enzyme: substrate ratio even after 60 min of incubation
S10T
-
Reduced DNA binding affinity, possibly changing Ser10 to a threonine residue, and changing Lys13 to arginine allow retention of activity, relaxation activity assays show that introduction of a different side chain with similar functionality but different steric properties at these two positions result in even lower relaxation activitymutations at Ser10 and Lys13 highly reduce the ability of topoisomerase I to support growth of the Escherichia coli cells, as expected from the loss of the relaxation activity. Thr10 forms a hydrogen bond with phosphate 8. Do not have severe changes in protein folding. Side chains of Ser10 and Lys13 are required for DNA cleavage activity, rates of cleavage are too low to be analyzed
Y319F
-
site-directed mutagenesis, constants of oligonucleotide binding compared to the wild-type enzyme
D117N
-
site-directed mutagenesis, induction of mutant YpTOP1-D117N topoisomerase by arabinose is similar in the absence or presence of trimethoprim
-
Cropo4
-
chimeric enzyme, human topo I having residues 631-717 replaced by residues 314-317 of Cre
Cropo6
-
chimeric enzyme, human topo I having residues 631-717 replaced by residues 312-317 of Cre
Cropo8
-
chimeric enzyme, human topo I having residues 631-717 replaced by residues 312-319 of Cre
DELTA1-202
-
mutant enzyme is impaired in blunt end ligation but remains sensitive towards camptothecin in relaxation
DELTA191-206
-
mutant is distinguished from wild-type enzyme by a decreased relaxation rate at distributive and an increased rate under processive conditions. Mutant is strongly impaired in blunt end ligation and insensitive towards camptothecin in relaxation
E418K
-
the active site tyrosine. The Glu418Lys mutant is active and partially resistant to CPT in yeast cells expressed in yeast cells, display a camptothecin resistance that slowly decreases as a function of time
E710G
-
site-directed mutagenesis, the mutation is not detectable in tissue samples from colorectal cancer patients
G717D
-
the mutant enzyme is no more sensitive to camptothecin than the wild type enzyme
hTopoI (deltaNL)
-
hTopoI deletion mutant. Considering the domain organization, hTopoI distinguishes itself from both Vaccinia virus TopoI and the tyrosine recombinases, by having rather extensive N-terminal and linker domains. Investigation of the resolution activity of hTopoI deleted in either one or both of these domains. Two hTopoI variants, hTopoI(deltaN) lacking aa 1-202, and hTopoI(deltaNL) lacking aa 1-202 and 660-688. Deleting the N-terminal and linker domains of hTopoI in order to mimic the domain organization of Vaccinia virus TopoI and the tyrosine recombinases inhibited resolution of the Holliday junction substrate. hTopoI(deltaNL) forms dimers
hTopoI(deltaN)
-
hTopoI deletion mutant. Considering the domain organization, hTopoI distinguishes itself from both Vaccinia virus TopoI and the tyrosine recombinases, by having rather extensive N-terminal and linker domains. Investigation of the resolution activity of hTopoI deleted in either one or both of these domains. Two hTopoI variants, hTopoI(deltaN) lacking aa 1-202, and hTopoI(deltaNL) lacking aa 1-202 and 660-688. Deleting the N-terminal and linker domains of hTopoI in order to mimic the domain organization of Vaccinia virus TopoI and the tyrosine recombinases inhibited resolution of the Holliday junction substrate. hTopoI(deltaNL) forms dimers
K532A
K532R
cleavage and religation activity of the mutant enzyme are reduced, cleavage is reduced to a greater extent than religation
K681A
-
site-directed mutagenesis, the mutation of Lys681, located on the tip of the linker domain, dramatically reduces the religation rate, the equilibrium of the mutant is shifted toward cleavage when compared to the wild-type enzyme. Mutation of residue 681 from lysine to alanine does not cause alterations in the linker domain secondary structure, and the main chain conformation of the mutated residue does not significantly change in relation with the neighbor residues, when compared to the wild-type protein
L617I
-
site-directed mutagenesis, the mutation is not detectable in tissue samples from colorectal cancer patients
N722S
camptothecin-resistant enzyme form, mutation leads to elimination of a water-mediated contact between the enzyme and topotecan
R364K/G717R
-
the mutations lead to resistance towards inhibitors SN-38 and NSC 743400
R621H
-
site-directed mutagenesis, the mutation is not detectable in tissue samples from colorectal cancer patients
T729A
-
mutations that confer camptothecin resistance, but do not interact directly with the drug or the DNA, oligonucleotide-directed mutagenesis
T729E
-
camptothecin resistance, remarkable defect in DNA binding, oligonucleotide-directed mutagenesis
T729K
T729P
W203A/W205A/W206A
lacking processivity, exhibits resistance to camptothecin and is inactivated by urea. Indicates that the tryptophan anchor stabilizes the N-terminus of the functional domain and revents the loss of Top1 structure and function
W205G
-
mutant is distinguished from wild-type enzyme by a decreased relaxation rate at distributive and an increased rate under processive conditions. Mutant is strongly impaired in blunt end ligation and insensitive towards camptothecin in relaxation
Y337F
-
mutant enzyme is still able to bind single-stranded DNA but is unable to cleave the DNA substrate because of the absence of the active Tyr337
Y723F
D325E
-
substantial level of resistance to camptothecin, 50% inhibition at 0.01 mM
delta 39-635
-
in contrast to camptothecin, baicalein and luteolin fail to inhibit the religation step when the drugs are added to pre-formed enzyme substrate binary complex. This differential mechanism to induce the stabilization of cleavable complex with topoisomerase I and DNA by these selected flavones and camptothecin result in investigations of the effect of baicalein and luteolin on camptothecin-resistant mutant enzyme LdTOP1D39LS lacking 139 amino acids of the large subunit
G185R
-
substantial level of resistance to camptothecin, 50% inhibition at 0.035 mM
G185R/D325
-
parasites containing both mutations simultaneously show high level of resistance to camptothecin
G185R/D325E
-
highly camptothecin-resistant with two substitutions in the core domain of the protein
H453A
-
Very little relaxing activity detectable, activity of the H453A protein to be more than 100fold reduced compared with that of LdTOPIL-fus-S
H453Q
-
Lower activity than LdTOPIL-fus-S, failing to completely relax the supercoiled DNA even after 40 min
K352A
-
site-directed mutagenesis, the mutant shows highly reduced relaxation activity compared to wild-type enzyme, the cleavage religation equilibrium is shifted towards the cleavage
K352R
-
site-directed mutagenesis, the mutant shows highly reduced relaxation activity compared to wild-type enzyme, the cleavage religation equilibrium is shifted towards the cleavage
R314K
-
site-directed mutagenesis, the mutant shows onyl slightly affected relaxation activity and only a slightly slower rate of cleavage compared to wild-type enzyme
Y327F
D261A LdTOPIS
-
Site-directed mutagenesis studies identify Lys455 of LdTOPIL and Asp261 of LdTOPIS as two residues involved in subunit interaction. The reconstituted mutant enzymes LdTOPILK436A/S, LdTOPILN441A/S, L/LdTOPISK249A and L/LdTOPISN256A do not show any appreciable change in the relaxation pattern compared with the wild-type enzyme L/S. Reconstitution of L with LdTOPISD261A (SD261A) causes a 15fold decrease in the relaxation activity compared with L/S
GST-LdTOPIS delta 1-201
-
Generated N-and C-terminal-truncated deletion constructs of of L and S subunit. The heterodimerization between the two fragments is weak and therefore co-purified fragments show reduced DNA binding, cleavage and relaxation properties compared with the wild type enzyme
GST-LdTOPIS delta 1-210
-
constitute the minimal interacting fragment. Generated N-and C-terminal-truncated deletion constructs of of L and S subunit. The heterodimerization between the two fragments is weak and therefore co-purified fragments show reduced DNA binding, cleavage and relaxation properties compared with the wild type enzyme
GST-LdTOPIS delta 1-210/delta 255-262
-
Generated N-and C-terminal-truncated deletion constructs of of L and S subunit. The heterodimerization between the two fragments is weak and therefore co-purified fragments show reduced DNA binding, cleavage and relaxation properties compared with the wild type enzyme
GST-LdTOPIS delta 1-215
-
Generated N-and C-terminal-truncated deletion constructs of of L and S subunit. The heterodimerization between the two fragments is weak and therefore co-purified fragments show reduced DNA binding, cleavage and relaxation properties compared with the wild type enzyme
GST-LdTOPIS delta 1-80
-
Generated N-and C-terminal-truncated deletion constructs of of L and S subunit. The heterodimerization between the two fragments is weak and therefore co-purified fragments show reduced DNA binding, cleavage and relaxation properties compared with the wild type enzyme
GST-LdTOPIS delta 245-262
-
Generated N-and C-terminal-truncated deletion constructs of of L and S subunit. The heterodimerization between the two fragments is weak and therefore co-purified fragments show reduced DNA binding, cleavage and relaxation properties compared with the wild type enzyme
GST-LdTOPIS delta 255-262
-
Generated N-and C-terminal-truncated deletion constructs of of L and S subunit. The heterodimerization between the two fragments is weak and therefore co-purified fragments show reduced DNA binding, cleavage and relaxation properties compared with the wild type enzyme
K243A LdTOPIS
-
Site-directed mutagenesis studies identify Lys455 of LdTOPIL and Asp261 of LdTOPIS as two residues involved in subunit interaction. The reconstituted mutant enzymes LdTOPILK436A/S, LdTOPILN441A/S, L/LdTOPISK249A and L/LdTOPISN256A do not show any appreciable change in the relaxation pattern compared with the wild-type enzyme L/S. Reconstitution of L with LdTOPISD261A (SD261A) causes a 15fold decrease in the relaxation activity compared with L/S
K436A LdTOPIL
-
Site-directed mutagenesis studies identify Lys455 of LdTOPIL and Asp261 of LdTOPIS as two residues involved in subunit interaction. The reconstituted mutant enzymes LdTOPILK436A/S, LdTOPILN441A/S, L/LdTOPISK249A and L/LdTOPISN256A do not show any appreciable change in the relaxation pattern compared with the wild-type enzyme L/S. Reconstitution of L with LdTOPISD261A (SD261A) causes a 15fold decrease in the relaxation activity compared with L/S
K455A LdTOPIL
-
Site-directed mutagenesis studies identify Lys455 of LdTOPIL and Asp261 of LdTOPIS as two residues involved in subunit interaction. The reconstituted mutant enzymes LdTOPILK436A/S, LdTOPILN441A/S, L/LdTOPISK249A and L/LdTOPISN256A do not show any appreciable change in the relaxation pattern compared with the wild-type enzyme L/S. Reconstitution of L with LdTOPISD261A (SD261A) causes a 15fold decrease in the relaxation activity compared with L/S
LdTOPIL delta 1-39
-
Generated N-and C-terminal-truncated deletion constructs of of L and S subunit. The heterodimerization between the two fragments is weak and therefore co-purified fragments show reduced DNA binding, cleavage and relaxation properties compared with the wild type enzyme
LdTOPIL delta 1-39/delta457-635
-
constitute the minimal interacting fragment. Generated N-and C-terminal-truncated deletion constructs of of L and S subunit. The heterodimerization between the two fragments is weak and therefore co-purified fragments show reduced DNA binding, cleavage and relaxation properties compared with the wild type enzyme
LdTOPIL delta 1-99
-
Generated N-and C-terminal-truncated deletion constructs of of L and S subunit. The heterodimerization between the two fragments is weak and therefore co-purified fragments show reduced DNA binding, cleavage and relaxation properties compared with the wild type enzyme
LdTOPIL delta 436-635
-
Generated N-and C-terminal-truncated deletion constructs of of L and S subunit. The heterodimerization between the two fragments is weak and therefore co-purified fragments show reduced DNA binding, cleavage and relaxation properties compared with the wild type enzyme
LdTOPIL delta 457-635
-
Generated N-and C-terminal-truncated deletion constructs of of L and S subunit. The heterodimerization between the two fragments is weak and therefore co-purified fragments show reduced DNA binding, cleavage and relaxation properties compared with the wild type enzyme
N256A LdTOPIS
-
Site-directed mutagenesis studies identify Lys455 of LdTOPIL and Asp261 of LdTOPIS as two residues involved in subunit interaction. The reconstituted mutant enzymes LdTOPILK436A/S, LdTOPILN441A/S, L/LdTOPISK249A and L/LdTOPISN256A do not show any appreciable change in the relaxation pattern compared with the wild-type enzyme L/S. Reconstitution of L with LdTOPISD261A (SD261A) causes a 15fold decrease in the relaxation activity compared with L/S
N441A LdTOPIL
-
Site-directed mutagenesis studies identify Lys455 of LdTOPIL and Asp261 of LdTOPIS as two residues involved in subunit interaction. The reconstituted mutant enzymes LdTOPILK436A/S, LdTOPILN441A/S, L/LdTOPISK249A and L/LdTOPISN256A do not show any appreciable change in the relaxation pattern compared with the wild-type enzyme L/S. Reconstitution of L with LdTOPISD261A (SD261A) causes a 15fold decrease in the relaxation activity compared with L/S
E215A
-
mutant activity with the mutation in the Topo-44 fragment (an N-terminal 44-kDa fragment of Topo-V) is active over a wider range of pH values, compared with wild-type enzyme. Mutant activity with the mutation in the Topo-44 fragment (an N-terminal 44-kDa fragment of Topo-V) is active over a wider range of pH values, compared with wild-type enzyme
E215H
-
mutant enzyme is active over a wider range of pH values, compared with wild-type enzyme, mutation in the Topo-44 fragment (an N-terminal 44-kDa fragment of Topo-V)
E215Q
-
mutant enzyme is active over a wider range of pH values, compared with wild-type enzyme, mutation in the Topo-44 fragment (an N-terminal 44-kDa fragment of Topo-V)
E215R
-
mutant enzyme is active over a wider range of pH values, compared with wild-type enzyme, mutation in the Topo-44 fragment (an N-terminal 44-kDa fragment of Topo-V)
H200A
-
mutant enzyme is slightly less active than wild type enzyme, mutation in the Topo-44 fragment (an N-terminal 44-kDa fragment of Topo-V)
H200E
-
mutant has low but detectable DNA relaxation activity at pH 5, mutation in the Topo-44 fragment (an N-terminal 44-kDa fragment of Topo-V)
H200N
-
mutant enzyme is slightly less active than wild type enzyme, mutation in the Topo-44 fragment (an N-terminal 44-kDa fragment of Topo-V)
H200Q
-
mutation in the Topo-44 fragment (an N-terminal 44-kDa fragment of Topo-V)
H200R
-
mutant enzyme shows relaxation activity over a pH range similar to the wild-type enzyme. In the Topo-78 backbone (an N-terminal 78-kDa fragment of Topo-V), qualitatively, H200R is as active as the wild type
K218Q
-
the mutant is inactive in all of the pH conditions tested, mutation in the Topo-78 fragment (an N-terminal 78-kDa fragment of Topo-V)
R131A
-
mutant shows no detectable DNA relaxation activity, mutations in Topo-44 fragment (an N-terminal 44-kDa fragment of Topo-V) or in Topo-78 fragment (an N-terminal 78-kDa fragment of Topo-V)
R131K
-
conservative substitution that retains both the electrostatic and acid/base properties, except for the loss of the bidentate coordination possible through the guanidinium group of the arginine. Whereas the R131K mutant is purified successfully in the Topo-44 backbone, it results in degradation when expressed in the Topo-78 backbone
R144A
-
mutant enzyme shows no activity, mutation in Topo-78 fragment (an N-terminal 78-kDa fragment of Topo-V)
T226F
-
the mutation abolishes activity at all pH values in T44Y226F and shows only minimal activity at pH 8, mutation in the Topo-44 fragment (an N-terminal 44-kDa fragment of Topo-V)
Y226F
-
mutation abolishes DNA binding, mutation in the Topo-44 fragment (an N-terminal 44-kDa fragment of Topo-V)
D111A
site-directed mutagenesis, mutation of the Mg2+-binding residue affects DNA relaxation activity, mutant D111A is dependent on Mg2+ for DNA cleavage and is compromised in religation
D111N
-
site-directed mutagenesis, the mutation is lethal for the host
E115A
site-directed mutagenesis, mutation of the Mg2+-binding residue affects DNA relaxation activity, the mutant is compromised in religation
G116S
-
site-directed mutagenesis, MtTOP1 TOPRIM motif mutation, the mutation inhibits DNA religation. The DNA cleavage activity of MtTOP1-G116 S is Mg2+-dependent
H139C
-
site-directed mutagenesis, the mutant can be labeled with fluorophores with no significant loss of relaxation activity, the mutant complements the temperature sensitive topA function of Escherichia coli strain AS17
K524C
-
site-directed mutagenesis, the mutant can be labeled with fluorophores with no significant loss of relaxation activity, the mutant complements the temperature sensitive topA function of Escherichia coli strain AS17
L170C
-
site-directed mutagenesis, the mutant can be labeled with fluorophores with no significant loss of relaxation activity, the mutant complements the temperature sensitive topA function of Escherichia coli strain AS17
T142C
-
site-directed mutagenesis, the mutant can be labeled with fluorophores with no significant loss of relaxation activity, the mutant complements the temperature sensitive topA function of Escherichia coli strain AS17
Y174C
-
site-directed mutagenesis, the mutant can be labeled with fluorophores with no significant loss of relaxation activity, the mutant complements the temperature sensitive topA function of Escherichia coli strain AS17
D111A
Mycobacterium tuberculosis H37Ra / ATCC 25177
-
site-directed mutagenesis, mutation of the Mg2+-binding residue affects DNA relaxation activity, mutant D111A is dependent on Mg2+ for DNA cleavage and is compromised in religation
-
E115A
Mycobacterium tuberculosis H37Ra / ATCC 25177
-
site-directed mutagenesis, mutation of the Mg2+-binding residue affects DNA relaxation activity, the mutant is compromised in religation
-
G721D
-
Single amino acid substitutions of yeast Gly721 alters Top1p sensitivity to camptothecin
G721E
-
Single amino acid substitutions of yeast Gly721 alters Top1p sensitivity to camptothecin
G721F
-
Single amino acid substitutions of yeast Gly721 alters Top1p sensitivity to camptothecin
G721L
-
Single amino acid substitutions of yeast Gly721 alters Top1p sensitivity to camptothecin
G721N
-
Single amino acid substitutions of yeast Gly721 alters Top1p sensitivity to camptothecin
G721Q
-
Single amino acid substitutions of yeast Gly721 alters Top1p sensitivity to camptothecin
G721V
-
Single amino acid substitutions of yeast Gly721 alters Top1p sensitivity to camptothecin
L720E
-
Single amino acid substitutions of Leu720 alters Top1p sensitivity to camptothecin
L720Q
-
Single amino acid substitutions of Leu720 alters Top1p sensitivity to camptothecin
N726D
N726F
-
specific activity is about 5fold lower than that of wild-type enzyme, self-poisoning phenotype, mutation enhances the kinetics of DNA cleavage
N726H
-
self-poisoning phenotype, specific activity is about 5fold lower than that of wild-type enzyme, binding of DNA increases from 2.5fold at 50 mM KCl to 4fold at 100 mM KCl, 10fold increase in DNA cleavage activity
N726K
-
camptothecin resistance of cells expressing the mutant enzyme
N726Q
-
camptothecin resistance of cells expressing the mutant enzyme
T722A
-
self-poisoning phenotype, reduced rate of DNA religation relative to wild-type enzyme, specific activity of the mutant enzyme is slightly decreased, however protein binding of DNA and rates of enzyme-catalyzed
T722A/N726H
-
specific activity is about 5fold lower than that of wild-type enzyme, N726H mutation potentiates the cytotoxic activity of T722A, increase in DNA cleavage activity
Y727F
C559A/C561A
no detectable zinc is bound to the mutant enzyme and its fluorescence properties are modified, suggesting a change of conformation in the protein lacking zinc. GThe mutant enzyme exhibits an activity similar to that of the wild-type enzyme with the same optimal temperature for activity. Thermostability is not affected by the mutation. Decatenase activity of wild type and C559A/C561A mutant enzymes shows no significant difference. Cleavage positions obtained with the C559A/C561A mutant is similar to those observed with the wild type enzyme. Preference for cytosine at position -4 is retained, and cleavage intensities are comparable
C559A/C561A
-
no detectable zinc is bound to the mutant enzyme and its fluorescence properties are modified, suggesting a change of conformation in the protein lacking zinc. GThe mutant enzyme exhibits an activity similar to that of the wild-type enzyme with the same optimal temperature for activity. Thermostability is not affected by the mutation. Decatenase activity of wild type and C559A/C561A mutant enzymes shows no significant difference. Cleavage positions obtained with the C559A/C561A mutant is similar to those observed with the wild type enzyme. Preference for cytosine at position -4 is retained, and cleavage intensities are comparable
-
D298A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
E124A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
E299A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
F101A
-
mutant enzyme displayes an aberrant response to magnesium, rate of relaxation is lower by a factor of 4-5 in the presence of 5 mM magnesium than in its absence, the rate of relaxation in presence of NaCl plus magnesium is reduced by a factor of 10.20 compared to wild-type enzyme, affinity for 60-bp duplex is 8fold lower than that of wild-type enzyme
F297A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
F88A
-
mutant enzyme displayes an aberrant response to magnesium, rate of relaxation is lower by a factor of 4-5 in the presence of 5 mM magnesium than in its absence, the rate of relaxation in presence of NaCl plus magnesium is reduced by a factor of 10-20 compared to wild-type enzyme, affinity for 60-bp duplex is 3fold lower than that of wild-type enzyme
K104A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
K107A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
K108A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
K220A
-
supercoil relaxation by mutant enzyme in presence of NaCl and no divalent cation is slower by a factor of 5 than relaxation by wild-type enzyme, mutant enzyme is inhibited by including Mg2+ with NaCl, rate of relaxation in presence of NaCl plus Mg2+ is reduced by 20fold compared to wild-type enzyme
K220H
-
supercoil relaxation by mutant enzyme in presence of NaCl and no divalent cation is slower by a factor of 5 than relaxation by wild-type enzyme, mutant enzyme is inhibited by including Mg2+ with NaCl, rate of relaxation in presence of NaCl plus Mg2+ is reduced by 40fold compared to wild-type enzyme
K220Q
-
supercoil relaxation by mutant enzyme in presence of NaCl and no divalent cation is slower by a factor of 5 than relaxation by wild-type enzyme, mutant enzyme is inhibited by including Mg2+ with NaCl, rate of relaxation in presence of NaCl plus Mg2+ is reduced by 40fold compared to wild-type enzyme
K220R
-
supercoil relaxation by mutant enzyme in presence of NaCl and no divalent cation is slower by a factor of 2 than relaxation by wild-type enzyme, neither stimulated nor inhibited by Mg2+, rate of relaxation in presence of NaCl plus Mg2+ is reduced by 8fold compared to wild-type enzyme
N103A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
N228A
-
relaxation of supercoiled DNA in presence of NaCl and no divalent cation is slower by a factor of 8 than relaxation by the wild-type enzyme
N228D
-
relaxation of supercoiled DNA in presence of NaCl and no divalent cation is slower by a factor of 40 than relaxation by the wild-type enzyme, mutant enzyme is inhibited by Mg2+, oligonucleotide cleavage is slower than that of wild-type enzyme by a factor of 200
N228Q
-
relaxation of supercoiled DNA in presence of NaCl and no divalent cation is slower by a factor of 5 than relaxation by the wild-type enzyme, not stimulated by including magnesium with NaCl
N228S
-
relaxation of supercoiled DNA in presence of NaCl and no divalent cation is slower by a factor of 2 than relaxation by the wild-type enzyme
N99A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
Q116A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
R90A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
R97A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
S204A
-
mutant protein relaxes supercoiled DNA slowly and is strongly inhibited in the presence of salt plus magnesium, the rate of single-turnover religation by covalently bound S204N is indistinguishable from wild-type within the limits of the assay
T296A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
Y274F
-
vaccinia topoisomerase mutant, lacks active site tyrosine nucleophile but binds to DNA containing specific recognition sequence, like wild type vTopo
A383P
-
mutant enzyme has wild-type levels of relaxation and cleavage activity
G122S
M326R
-
overexpression of the M326R mutant YTOP resulted in 4 log loss of viability
M326V
-
mutant enzyme has wild-type levels of relaxation and cleavage activity
R327F
-
site-directed mutagenesis, the mutation leads to the SOS response and has a strong cell killing effect when the mutant is overexpressed in Escherichia coli and induced with 0.2% arabinose, the mutant shows reduced DNA cleavage and requirement for Mg2+
R327I
-
site-directed mutagenesis, the mutation leads to the SOS response and has a strong cell killing effect when the mutant is overexpressed in Escherichia coli and induced with 0.2% arabinose, the mutant shows reduced DNA cleavage and requirement for Mg2+
R327L
-
site-directed mutagenesis, the mutation leads to the SOS response and has a strong cell killing effect when the mutant is overexpressed in Escherichia coli and induced with 0.2% arabinose, the mutant shows reduced DNA cleavage and requirement for Mg2+
R327S
R327W
-
site-directed mutagenesis, the mutation leads to the SOS response and has a strong cell killing effect when the mutant is overexpressed in Escherichia coli and induced with 0.2% arabinose, the mutant shows reduced DNA cleavage and requirement for Mg2+
additional information
D111N
-
site-directed mutagenesis, the mutant is trapped in complex with DNA, accumulation of the covalent complex of bacterial topoisomerase I is lethal. A full-length enzyme with this D111N mutation could not be expressed, but the N-terminal 67-kDa transesterification domain. Structure comparison of wild-type and D111N mutant enzymes, overview
K532A
cleavage and religation activity of the mutant enzyme are reduced, religation is reduced to a greater extent than cleavage
K532A
expression of the mutant enzyme in Saccharomyces cerevisiae is cytotoxic, this mutant enzyme mimics the effects of the anticancer drug camptothecin
T729K
is resistant even at high concentration to camptothecin anti-cancer drug
Y723F
-
the active site mutant shows abolished formation of Top1 covalent adducts with DNA structures
Y327F
site-directed mutagenesis, the active site mutant construct cannot suppress the slow-growth of top3 mutant Saccharomyces cerevisiae
Y327F
-
site-directed mutagenesis, the active site mutant construct cannot suppress the slow-growth of top3 mutant Saccharomyces cerevisiae
-
N726D
-
mutant enzyme is resistant to camptothecin, no appreciable decrease in catalytic activity, exhibits a distributive mode of plasmid DNA relaxation compared to a progressive mode of the wild-type enzyme. Activity of the mutant enzyme is optimal at 75-100 mM KCl, compared to 150 mM KCl for the wild-type enzyme
N726D
-
self-poisoning phenotype, reduced rate of DNA religation relative to wild-type enzyme, affinity for DNA is reduced about 2.5fold relative to that observed for wild-type Top1p at 50 or 75 mM KCl
R327S
-
naturally occuring mutation identified in the AW3-75 mutant, the mutation leads to the SOS response and has a cell killing effect when the mutant is overexpressed in Escherichia coli and induced with 0.2% arabinose
additional information
-
conclude that the active sites of MimiTopIB and vaccinia TopIB are composed of similar functional groups
additional information
An experiment was performed to assess the ability of bcTopo IIIbeta to substitute for ecTopo III in vivo. bcTopo IIIbeta can not substitute for the loss of ecTopo III in Escherichia coli
additional information
-
An experiment was performed to assess the ability of bcTopo IIIbeta to substitute for ecTopo III in vivo. bcTopo IIIbeta can not substitute for the loss of ecTopo III in Escherichia coli
additional information
-
An experiment was performed to assess the ability of bcTopo IIIbeta to substitute for ecTopo III in vivo. bcTopo IIIbeta can not substitute for the loss of ecTopo III in Escherichia coli
-
additional information
comparison of wild-type Escherichia coli topoisomerase III with the Escherichia coli topoisomerase III (Y328F) mutant. Conformational differences: the ssDNA is not as deeply buried in the active site of the open complexes as it is in the topoisomerase IIIY328F+ ssDNA complex. EnzymeDNA interactions along the binding groove in the fully bound wild-type-DNA complex are analogous to those seen in the topoisomerase IIIY328F-DNA structure. Conformation resembles the one observed previously with a DNA-bound, catalytically inactive mutant of topoisomerase III where DNA binding realigns catalytic residues to form a functional active site
additional information
-
comparison of wild-type Escherichia coli topoisomerase III with the Escherichia coli topoisomerase III (Y328F) mutant. Conformational differences: the ssDNA is not as deeply buried in the active site of the open complexes as it is in the topoisomerase IIIY328F+ ssDNA complex. EnzymeDNA interactions along the binding groove in the fully bound wild-type-DNA complex are analogous to those seen in the topoisomerase IIIY328F-DNA structure. Conformation resembles the one observed previously with a DNA-bound, catalytically inactive mutant of topoisomerase III where DNA binding realigns catalytic residues to form a functional active site
additional information
-
expression of His-tagged Yersinia pestis topoisomerase I mutants, that are deficiency in DNA rejoining, under the control of the BAD promoter in plasmid pYTOP in Escherichia coli strain JD5 and purification by nickel affinity chromatography leading to a lethal phenotype of the Escherichia coli cells, overview
additional information
-
dissociation constants obtained for binding of wild-type EcTOP1, R169A, R173A and Y177S mutant enzymes to 3'-labeled 59 base hairpin oligonucleotide substrates, Oligo C, Oligo A and Oligo G, overview
additional information
-
preparation of YrdD protein, the homologue of the topoisomerase I C-terminal region, that contains only iron or zinc by expressing the protein in Escherichia coli cells grown in the M9 minimal media supplemented with either iron or zinc, respectively
additional information
-
usage of isogenic topA+ strain RFM44526 to study the involvement of topoisomerase I function in the SOS response. To monitor the extent of cell killing from accumulation of the topoisomerase I cleavage complex, Escherichia coli strain BW117N with a mutant Yersinia pestis topoisomerase I, YpTOP1-D117N, gene under the control of the BAD promoter inserted into the chromosome36 is used
additional information
-
usage of isogenic topA+ strain RFM44526 to study the involvement of topoisomerase I function in the SOS response. To monitor the extent of cell killing from accumulation of the topoisomerase I cleavage complex, Escherichia coli strain BW117N with a mutant Yersinia pestis topoisomerase I, YpTOP1-D117N, gene under the control of the BAD promoter inserted into the chromosome36 is used
-
additional information
molecular models of human topoisomerase I bearing K532-PL, K532-PLP and K532-PLP-AMP modified residues build with the molecular modelling package Insight II
additional information
-
molecular models of human topoisomerase I bearing K532-PL, K532-PLP and K532-PLP-AMP modified residues build with the molecular modelling package Insight II
additional information
-
Topoisomerase I is modified at the active site by incorporation of a number of tyrosine analogues employed 13 structural analogous of tyrosine. SDS-PAGE, in vitro synthesis of human topoisomerase I analogues modified at position 723. Human topoisomerase I-mediated DNA relaxation assay
additional information
plasmid constructs used: pTop65 has an initiator methionine codon followed by Top1 codons 214-765, pTop68 has an initiator methionine codon followed by six histidine codons and four codons encoding the Factor Xa protease-cleavage site, and then Top1 codons 201-765, pTop68W/A is the same as pTop68 except that Trp203, Trp205 and Trp206 are mutated to alanine, pTop69NLS has an initiator methionine codon followed by six histidine codons and four codons encoding the Factor Xa protease-cleavage site, and then Top1 codons 189-765
additional information
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plasmid constructs used: pTop65 has an initiator methionine codon followed by Top1 codons 214-765, pTop68 has an initiator methionine codon followed by six histidine codons and four codons encoding the Factor Xa protease-cleavage site, and then Top1 codons 201-765, pTop68W/A is the same as pTop68 except that Trp203, Trp205 and Trp206 are mutated to alanine, pTop69NLS has an initiator methionine codon followed by six histidine codons and four codons encoding the Factor Xa protease-cleavage site, and then Top1 codons 189-765
additional information
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enzyme downregulation by topoisomerase I siRNA in HeLa cells
additional information
-
expression of specific siRNA inhibits the enzyme and elicits distinct changes in TF biosynthesis in TNF-alpha-stimulated endothelial cells, which impact endothelial procoagulant activity
additional information
-
generation of mutant cells that are deficient in mitochondrial isozyme Top1mt, i.e. the Top1mt-/- cell line
additional information
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in vitro gene fusion of Leishmania bisubunit topoisomerase I into a single ORF encoding a new monomeric topoisomerase I (LdTOPIL-fus-S), N-terminal truncation mutant (1210 amino acids) of the small subunit, when fused to the intact large subunit [LdTOPIL-fus-D(1210)S], shows reduced topoisomerase I activity and camptothecin sensitivity in comparison to LdTOPIL-fus-S experiments in which Leishmania bisubunit topoisomerase I large subunit (LdTOPIL) and small subunit (LdTOPIS) genes are fused into a single ORF encoding a new topoisomerase I (LdTOPIL-fus-S), suicidal cleavage activity and religation activity of LdTOPIL-fus-S and its mutant variants
additional information
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Leishmania donovani strain Ld160CPTR camptothecin-resistant Leishmania donovani strain. The camptothecin-resistant strain reached a resistance level of 32fold over the wild-type Leishmania donovani AG83 strain. Baicalein and luteolin show inhibition of relaxation activity up to 60% at 30 mM concentration compared with that of camptothecin, where no inhibition of relaxationactivity is observed
additional information
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three truncated Topo V polypeptides comprising the NH2-terminal 44000 Da and 16000 Da domains, the 44000 Da, 16000 Da and 18000 Da domains and the C-terminal 34000 Da domain. Topo61 and Topo78 are active topoisomerases, but in contrast to Topo V these enzymes are inhibited by high salt concentrations. Topo34 has strong DNA-binding ability but shows no topoisomerase activity. Topo78 and Topi34 possess apurinic/apyrimidinic lyase activity that is important in base excision DNA repair
additional information
preparation of several mutant mTopoI promoters, including wild type and E1, E2, Dbox, E1/Dbox, E1/E2, and E1/E2/Dbox mutant types, and measurement of bioluminescence using a real-time monitoring assay
additional information
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preparation of several mutant mTopoI promoters, including wild type and E1, E2, Dbox, E1/Dbox, E1/E2, and E1/E2/Dbox mutant types, and measurement of bioluminescence using a real-time monitoring assay
additional information
the His6 tagged-MtbTopA protein is immobilized on an NTA chip. When an increasing amount of GST tagged-Rv2436 protein pass over the chip, they cause a substantial response, overview
additional information
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the His6 tagged-MtbTopA protein is immobilized on an NTA chip. When an increasing amount of GST tagged-Rv2436 protein pass over the chip, they cause a substantial response, overview
additional information
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the His6 tagged-MtbTopA protein is immobilized on an NTA chip. When an increasing amount of GST tagged-Rv2436 protein pass over the chip, they cause a substantial response, overview
-
additional information
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generation of deletion mutants of the enzyme lacking each one of the three basic stretches of the C-terminal domain. The mutants are highly compromised in binding two DNA molecules
additional information
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TopA depletion in strains PS01 (wild-type background) and PS03 (-parB background). TopA depletion in the -parB background (PS03) leads to a decrease in chromosome segregation abnormalities with 8.9% anucleate prespores compared to that in the parB deletion strain J3305, with 19.5% anucleate prespores
additional information
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modification of vaccinia topoisomerase I at the active site tyrosine (position 274) with several tyrosine analogues. These analogues have varied steric, electronic, and stereochemical features to permit assessment of those structural elements required to support topoisomerase function. Eleven tyrosine analogues are successfully incorporated into the active site of vaccinia topoisomerase I. It is found that only tyrosine analogues having the phenolic -OH group in the normal position relative to the protein backbone are active. Modifications that replace the nucleophilic tyrosine OH group with NH2, SH, or I groups or that changed the orientation of the nucleophilic OH group essentially eliminate topoisomerase I function
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
-
180 min, about 80% loss of activity. 60 min, about 50% loss of activity
37
-
180 min, complete loss of activity. 60 min, about 65% loss of activity
42
-
half-life in absence of VO3-: 5 min, half-life in presence of 0.1 mM VO3-: 60 min
44
-
50% loss of activity after 8 min, complete inactivation after 40 min
45
65
75
80
both wild type and C559A/C561A mutant enzymes remain fully active after 30 min
65
-
30 min, 10 mM Tris-HCl buffer, pH 7.5, 1 mM EDTA, 5 mM 2-mercaptoethanol, 0.5 mM PMSF, 10% glycerol, 150 mM NaCl, protein concentration 1.5 mg/ml, enzyme forms MW 80000, MW 100000 and MW 110000, stable
75
-
30 min, 10 mM Tris-HCl buffer, pH 7.5, 1 mM EDTA, 5 mM 2-mercaptoethanol, 0.5 mM PMSF, 10% glycerol, 150 mM NaCl, protein concentration 1.5 mg/ml, enzyme forms MW 80000, MW 100000 and MW 110000, 30% loss of activity
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
topoisomerase I exhibits a unique hot spot susceptible to proteolytic attack with a variety of proteases (around amino acids 326-330). A truncated version of the enzyme lacking the C-terminal 93 amino acids is more susceptible to proteolysis, which suggests that the C-terminal region of the topoisomerase may be important to maintain the compact folding of the enzyme. Trypsin-digested topoisomerase I retains full DNA binding, cleavage and relaxation activities and full thermostability
-
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70°C, 50 mM Tris-HCl, pH 7.8, 10 mM 2-mercaptoethanol, 0.5 mM dithiothreitol, 0.5 mM PMSF, 15% glycerol, stable for at least 6 months
-
4°C, without stabilizer, half-life: 1 week. 0.1 mM NaVO3, increases storage life approximately 3fold
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
by combination of phosphocellulose, hydroxylapitite and ssDNA agarose column chromatography as described elsewhere
-
chitin affinity chromatography followed by chromatography on hydroxyapatite
from a soluble bacterial lysate by Ni2+-agarose chromatography
-
His6-tagged recombinant enzyme from Escherichia coli strain BL21 (DE3) by nickel affinity chromatography, cleavage and elimination of the His-tag
-
N-terminally epitope-tagged with sequence DYKDDDY, i.e. FLAG-tag, recombinant enzyme from Saccharomyces cerevisiae strain EKY3 by immunoaffinity chromatography
-
Ni Sepharose 6 column chromatography and single-stranded DNA cellulose column chromatography
-
Ni2+-NTA agarose column followed by phosphocellulose column. Concentrations of purified proteins quantified by Bradford reaction
-
partial
phosphocellulose column chromatography and FLAG affinity column chromatography
-
Protein constructs. Structure of recombinant Leishmania donovani topoisomerase I proteins
-
Proteins are purified through Ni-NTA (Ni2+-nitrilotriacetate)agarose or GST (glutathione transferase)Sepharose 4B column followed by phosphocellulose column (P11 cellulose)
-
recombinant enzyme by polymin P and ammonium sulfate fractionations, cation- and anion-exchange chromatography, purified DNA topoisomerase I is free of DNase contamination, method development, overview
-
recombinant His-tagged enzyme from Escherichia coli strain BL21 by nickel affinity chromatography and gel filtration
-
recombinant His-tagged full-length enzyme and enzyme fragments from Saccharomyces cerevisiae by nickel affinity chromatography and cation exchange chromatography
-
recombinant His-tagged TopoI from Escherichia coli strain DH5alpha by ammonium sulfate fractionation and nickel affinity chromatography
recombinant His-tagged topoisomerase I mutants from Escherichia coli strain JD5 and purification by nickel affinity chromatography
-
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21AI by nickel affinity chromatography
-
recombinant nontagged enzyme from Escherichia coli strain BL21 by ammonium sulfate fractionation, dialysis, and heparin affinity chromatography, recombinant wild-type and mutant His-tagged enzymes from Escherichia coli strain BL21(DE3) by ammonium sulfate fractionation, dialysis, and nickel affinity chromatography, native enzyme from Mycobacterium tuberculosis strain H37Ra
recombinant tagged enzyme from Escherichia coli strain BL21(DE3) by heparin affinity chromatography
-
recombinant Yersinia pestis topoisomerase I proteins with the C-terminus hexahistidine tag are purified using the ProPur IMAC Midi spin column
-
three truncated Topo V polypeptides comprising the NH2-terminal 44000 Da and 16000 Da domains, the 44000 Da, 16000 Da and 18000 Da domains and the C-terminal 34000 Da domain
-
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
BPV1 glutathione S-transferase (GST)-E1, BPV1 GST-E1 DBD, BPV1 E2, and the human papillomavirus type 11 (HPV11) GST-E1 truncation mutant (aa 589 to 649) expressed in Escherichia coli BL21(DE3)
-
cloned into T7 RNA polymerase-regulated plasmid expression vectors, expression in Escherichia coli
-
DNA topoisomerase I activity is detected only when both genes LdTOP1A and LdTOP1B are coexpressed in a yeast expression system, LdTOP1A and LdTOP1B are located on different chromosomes
expressed in Escherichia coli. High-copy-number plasmid expressing YpTOP-D117N can not be maintained in Escherichia coli without a second-site mutation
Q7CIL8
expressed in Saccharomyces cerevisiae
expressed in Saccharomyces cerevisiae strain RS190
expression in Escherichia coli
expression in Escherichia coli under the control of a bacteriophage T7 promoter
-
expression of His-tagged TopA in Escherichia coli strain BL21
expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
-
expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21AI
-
expression of His-tagged Yersinia pestis topoisomerase I mutants, under the control of the BAD promoter in plasmid pYTOP, in Escherichia coli strain JD5 and purification by nickel affinity chromatography leading to a lethal phenotype of the Escherichia coli cells, overview
-
expression of the recombinant ETOP is induced in Escherichia coli BL21AI
expression of the soluble His6-tagged enzyme in Escherichia coli strain BL21 (DE3)
-
expression of the tagged enzyme in Escherichia coli strain BL21(DE3) from plasmid pPVN123, cloningi in Escherichia coli strain DH10B
-
expression of YrdD protein, the homologue of the topoisomerase I C-terminal region, that contains only iron or zinc by expressing the protein in Escherichia coli cells grown in the M9 minimal media supplemented with either iron or zinc, respectively
-
gene MsTopA, co-expression with gene Ms4585, encoding a ribokinase, in Escherichia coli strain BL21. Interaction analysis using the two-hybrid system
-
gene MtbTopA, co-expression with gene Rv2436, encoding a ribokinase of Mycobacterium tuberculosis, in Escherichia coli strain BL21. Interaction analysis using the two-hybrid system
gene Sau-TopoI, DNA and amino acid sequence determination and analysis, sequence comparisons, expression of His-tagged enzyme in Escherichia coli strain DH5alpha
gene Top1, DNA and amino acid sequence determination and analysis, promoter sequence analysis, genetic structure, sequence comparisons, expression pattern analysis using MPSS method
gene Top1, recombinant expression in Saccharomyces cerevisiae strain EKY3 from YCpGAL1-e-Top1 single copy plasmid, N-terminally epitope-tagged with sequence DYKDDDY
-
gene topA, expression fo His-tagged enzyme under the control of a modified pET28 Plac promoter in Escherichia coli strain BL21
-
gene topA, the gene is controlled by four promoters recognized by sigma32 and sigmas in addition to sigma70
-
Heterologous co-expression of LdTop1L and LdTop1S in a topoisomerase I deficient Saccharomyces cerevisiae strain (EKY3, MBY3), reconstitutes a fully functional enzyme which can be used for structural studies. Purified fragments of N-terminal truncation are used to transform XL-1Blue Escherichia coli
-
heterologously expressed in Escherichia coli exhibits topoisomerase activity
-
overexpressed in Escherichia coli
overexpression of wild-type and mutant His-tagged and non-tagged enzymes in Escherichia coli strain BL21(DE3)
plasmid-encoded recombinant MtTOP1 can complement the temperature sensitive topA function of Escherichia coli strain AS17 for growth at 42°C. The relaxation activity of recombinant wild-type MtTOP1 is functional in Escherichia coli. No complementation from the Y342A or G116S MtTOP1 mutants, but by mutant H139C, L170C, Y174C, T142C, and K524C. Overexpression of MtTOP1 mutant G116S leads to accumulation of cleavage complex formed by MtTOP1 in Escherichia coli
-
recombinant His-tagged full-length enzyme and enzyme fragments expression in Saccharomyces cerevisiae
-
three truncated Topo V polypeptides comprising the NH2-terminal 44000 Da and 16000 Da domains, the 44000 Da, 16000 Da and 18000 Da domains and the C-terminal 34000 Da domain
-
transformed into the yeast Saccharomyces cerevisiae top1alpha strain RS190 by the lithium acetate procedure
-
two genes encoded in ORFs LmjF28.1780 and LmjF36.3200, DNA and amino acid sequence determination and analysis, sequence comparisons. TopIIIbeta subcloning in Escherichia coli DH5alpha, expression in Escherichia coli strain BL21 and in Saccharomyces cerevisiae strain W5909-3B. Expression of C-terminal-GFP-tagged full length LdTopIII? protein in Leishmania donovani promastigotes. LdTopIIIbeta suppresses the yeast top3DELTA slow-growth phenotype
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the enzyme expression is transiently induced up to 11fold by interleukin-2 at 1000 U/ml after 10 h
-
trimethoprim, mitomycin C, or acidified nitrite induce the enzyme
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
-
the absence of cysteine residues in MtTOP1 makes it an attractive system for introduction of potentially informative chemical or spectroscopic probes at specific positions via cysteine mutagenesis. Such probes could be useful for development of high throughput screening assays and can be utilized for fluorescence probe incorporation and fluorescence resonance energy transfer measurement with fluorophore-labeled oligonucleotide substrate
diagnostics
-
the enzyme hTopI is a biomarker for camptothecin-based therapy at direct determination of the drug response level
drug development
medicine
pharmacology
drug development
-
3,3-diindolylmethane is a novel Leishmania donovani topoisomerase I poison which acts as a noncompetitive inhibitor. So this intriguing dietary component might be exploited for therapeutic development against leishmaniasis
drug development
-
anticancer agents that target TOP1 achieve their cytotoxic effects by stabilizing and trapping the cleavable TOP1-DNA complex, which ultimately leads to the accumulation of DNA strand breaks and cell death
drug development
-
dimeric compounds are promising candidates to be further elaborated as anticancer leads
drug development
-
DNA topoisomerase I is a potential target for chemotherapy
drug development
-
DNA topoisomerase I is a potential target for chemotherapy
drug development
-
DNA topoisomerase I is a potential target for chemotherapy
drug development
-
DNA topoisomerase I is a potential target for chemotherapy
drug development
-
DNA topoisomerase I is a potential target for chemotherapy
drug development
DNA topoisomerase I is a potential target for chemotherapy
drug development
-
DNA topoisomerase I is an important cellular target in drug discovery
drug development
-
potential target for drug treatment against smallpox and molluscum contagiosum virus
drug development
-
potential target for drug treatment against smallpox and molluscum contagiosum virus
drug development
-
to identify new molecular targets for antiparasitic drugs, attention focuses on DNA topoisomerases
drug development
-
topoisomerase poisoning has been recognized as an effective approach for the development of chemotherapeutics
drug development
-
topoisomerasedrug interactions for clinical development of chemotherapeutics
drug development
-
comparison of the target sites in plants exploited for obtaining additional information on drug-target interaction and for designing advanced drugs to prevent resistance in cancer cells and combat drug resistance
drug development
-
comparison of the target sites in plants exploited for obtaining additional information on drug-target interaction and for designing advanced drugs to prevent resistance in cancer cells and combat drug resistance
drug development
-
comparison of the target sites in plants exploited for obtaining additional information on drug-target interaction and for designing advanced drugs to prevent resistance in cancer cells and combat drug resistance
drug development
-
comparison of the target sites in plants exploited for obtaining additional information on drug-target interaction and for designing advanced drugs to prevent resistance in cancer cells and combat drug resistance
drug development
-
comparison of the target sites in plants exploited for obtaining additional information on drug-target interaction and for designing advanced drugs to prevent resistance in cancer cells and combat drug resistance
drug development
comparison of the target sites in plants exploited for obtaining additional information on drug-target interaction and for designing advanced drugs to prevent resistance in cancer cells and combat drug resistance
drug development
-
the enzyme is an attractive target for discovery of novel tuberculosis drugs that act by enhancing the accumulation of the topoisomerase-DNA cleavage product
drug development
-
the enzyme is a potential selective target for chemotherapy and drug development against malaria
drug development
-
the enzyme is a potential selective target for chemotherapy and drug development against malaria
drug development
-
the enzyme is often upregulated in cancer cells, and it is a target for chemotherapeutic drugs of the camptothecin family
medicine
TopoI is very important for the antitumor efficacy of many drugs, through the regulating the circadian clock genes and cell cycle control genes
pharmacology
-
The structure of the variola topoisomerase IBDNA cleavage complex, together with the unique biochemical features of the enzyme, provides a starting point for the rational design of antismallpox therapeutics
pharmacology
-
topoisomerase I is the target for camptothecin-based anticancer drugs that act by increasing levels of topoisomerase I-mediated DNA scission
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EXTERNAL LINKS (specific for EC-Number 5.6.2.1)
Transporter Classification Database (TCDB): 3.A.7.7.1
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Release 2023.1 (January 2023)
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