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Literature summary for 5.6.2.1 extracted from

  • Arno, B.; Coletta, A.; Tesauro, C.; Zuccaro, L.; Fiorani, P.; Lentini, S.; Galloni, P.; Conte, V.; Floris, B.; Desideri, A.
    A small organic compound enhances the religation reaction of human topoisomerase I and identifies crucial elements for the religation mechanism (2013), Biosci. Rep., 33, e00025.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
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 Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
gene Top1, recombinant expression in Saccharomyces cerevisiae strain EKY3 from YCpGAL1-e-Top1 single copy plasmid, N-terminally epitope-tagged with sequence DYKDDDY Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
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 Homo sapiens
camptothecin the natural compound reversibly binds the covalent Top1-DNA complex slowing down the religation of the cleaved DNA strand, thus inducing cell death Homo sapiens
irinotecan water-soluble camptothecin derivative Homo sapiens
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 Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
gene Top1
-

Purification (Commentary)

Purification (Comment) Organism
N-terminally epitope-tagged with sequence DYKDDDY, i.e. FLAG-tag, recombinant enzyme from Saccharomyces cerevisiae strain EKY3 by immunoaffinity chromatography Homo sapiens

Reaction

Reaction Comment Organism Reaction ID
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 Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
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 Homo sapiens ?
-
?

Synonyms

Synonyms Comment Organism
DNA Top IB
-
Homo sapiens
Top1
-
Homo sapiens
Topoisomerase I
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
assay at Homo sapiens