2.7.4.6: nucleoside-diphosphate kinase
This is an abbreviated version!
For detailed information about nucleoside-diphosphate kinase, go to the full flat file.
Word Map on EC 2.7.4.6
-
2.7.4.6
-
triphosphate
-
node
-
gdp
-
lymph
-
adenylate
-
metastases
-
tumour
-
autophosphorylation
-
colorectal
-
oncogene
-
drosophila
-
guanine
-
c-myc
-
clinicopathological
-
melanoma
-
creatine
-
dictyostelium
-
hexameric
-
gtp-binding
-
discoideum
-
non-metastatic
-
gamma-phosphate
-
anti-metastatic
-
heterotrimeric
-
phosphohistidine
-
transphosphorylation
-
dntp
-
deoxyribonucleoside
-
succinyl-coa
-
phosphoenzyme
-
metastasis-related
-
mastoparan
-
high-metastatic
-
metastasis-associated
-
prune
-
c-erbb-2
-
myxococcus
-
g-quadruplexes
-
deoxynucleoside
-
xanthus
-
medicine
-
drug development
- 2.7.4.6
- triphosphate
- node
- gdp
- lymph
- adenylate
- metastases
- tumour
- autophosphorylation
- colorectal
- oncogene
- drosophila
- guanine
- c-myc
-
clinicopathological
- melanoma
- creatine
- dictyostelium
-
hexameric
-
gtp-binding
- discoideum
-
non-metastatic
-
gamma-phosphate
-
anti-metastatic
-
heterotrimeric
-
phosphohistidine
-
transphosphorylation
- dntp
- deoxyribonucleoside
- succinyl-coa
- phosphoenzyme
-
metastasis-related
- mastoparan
-
high-metastatic
-
metastasis-associated
-
prune
-
c-erbb-2
- myxococcus
-
g-quadruplexes
- deoxynucleoside
- xanthus
- medicine
- drug development
Reaction
Synonyms
AfNDK, Afu5g03490, ASNDK, At4g09320, At4g11010, At5g63310, HsNDK, kinase, nucleoside diphosphate (phosphorylating), mitochondrial nucleoside diphosphate kinase, MJ1265, More, NDK, NDK B, NDK-1, NDKB, NDP kinase, NDP kinase A, NDP kinase alpha, NDP kinase beta, NDPK, NDPK B, NDPK I, NDPK II, NDPK III, NDPK IIpn, NDPK In, NDPK-3, NDPK-B, NDPK-C, NDPK-D, NDPK-In, NDPK1, NDPK2, NDPK3, NDPK3a, NDPKA, NDPKB, NM23, NM23 metastasis suppressor, Nm23-H1, NM23-H2, NM23-H4, NME1, NME2, NME3, NME4, nucleoside 5'-diphosphate kinase, nucleoside diphosphate (UDP) kinase, nucleoside diphosphate kinase, nucleoside diphosphate kinase 1, nucleoside diphosphate kinase 2, nucleoside diphosphate kinase 3, nucleoside diphosphate kinase 3a, nucleoside diphosphate kinase A, nucleoside diphosphate kinase B, nucleoside diphosphate kinase C, nucleoside diphosphate kinase D, nucleoside diphosphate kinase-1, nucleoside diphosphate kinase-2, nucleoside diphosphate kinases alpha, nucleoside diphosphate kinases beta, nucleoside diphosphate phosphotransferase, nucleoside diphosphokinase, nucleoside-diphosphate kinase 3, nucleotide diphosphate kinase, nucleotide phosphate kinase, ORF454, Os12g36194, OsNDPK2, SwoH, TcNDPK1, TcNDPK3, UDP kinase, uridine diphosphate kinase, WSL12, YSS2 protein
ECTree
2.7.4.6 nucleoside-diphosphate kinaseAdvanced search results
results (
results (Engineering
Engineering on EC 2.7.4.6 - nucleoside-diphosphate kinase
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
top
PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
E28A
-
site-directed mutagenesis the mutation interrupts the secondary structure of the protein leading to declined enzymatic activity compared to wild-type
H197C
L225stop
LP175S
no interaction between NDPK2 and small G proteins, EC 3.6.5.2
P175S
R230stop
V83F
the structure of the mutant enzyme is not stable at higher temperature
V83F
-
the structure of the mutant enzyme is not stable at higher temperature
-
G19V
the mutation rigidifies the 43-63 loop in Ndk, using GTP as the phosphate donor a 300fold reduction in phosphotransferase activity is observed
H115Q
H115Q is incompetent in autophosphorylation, confirming the role of histidine as a phosphate acceptor
C139S
C139S
H122G
study of chemical rescue for ATP attack, crystallization data
R31C
-
the mutation destabilizes the hexameric assembly, and causes dissociation to less active dimers at low salt concentrations
D112S
-
the mutant shows reduced specific activity compared to the wild type enzyme
D148C
-
the mutation enhances stability and folding in low salt solution by S-S bond. The mutant shows increased thermal stability by about 10°C in 0.2 M NaCl over the wild type enzyme
D58G
-
the mutant shows strongly reduced specific activity compared to the wild type enzyme
D58G/D63G
-
the mutant shows no refolding enhancement and strongly reduced specific activity compared to the wild type enzyme
D63G
-
the mutant shows slightly reduced specific activity compared to the wild type enzyme
G114D
G114K
active mutant enzyme, refolds in 1M NaCl after heat-denaturation, under which the wild-type enzyme and mutant enzyme G114S proteins show no refolding
G114R
G114S
active mutant enzyme, dissociates as extensively as the wild-type enzyme as low salt buffer
N111L
a HisN111L mutant with an N-terminal extension sequence containing hexa-His tag has enhanced salt requirements for enzymatic activity and refolding even though the secondary structure of the HisN111L mutant is confirmed to be similar to the control
G114D
-
inactive mutant enzyme, dissociates more than wild-type enzyme in low salt buffer
-
G114K
-
active mutant enzyme, refolds in 1M NaCl after heat-denaturation, under which the wild-type enzyme and mutant enzyme G114S proteins show no refolding
-
G114R
-
once folded, the mutant enzyme is stable even in low salt buffer
-
G114S
-
active mutant enzyme, dissociates as extensively as the wild-type enzyme as low salt buffer
-
N111L
-
a HisN111L mutant with an N-terminal extension sequence containing hexa-His tag has enhanced salt requirements for enzymatic activity and refolding even though the secondary structure of the HisN111L mutant is confirmed to be similar to the control
-
C139S
site-directed mutagenesis, the mutation in the dimeric nucleoside diphosphate kinase generates a catalytically competent enzyme monomer
E134A
E134A/E135A
site-directed mutagenesis, the mutant shows increased oligomerization compared to the wild-type enzyme
H118G/F60W
-
mutant engineered for following intrinsic fluorescence during substrate binding, crystallization data
H118N/S120G
site-directed mutagenesis, the mutant is inactive and expressed as insoluble protein in inclusion bodies
K135L
-
isoform B, mutation in dimeric interface, defective DNA-binding and reduced stability of enzyme
N69H
-
isoform B, mutation in dimeric interface, defective DNA-binding and reduced stability of enzyme
R34G
-
isoform B, mutation in dimeric interface, defective DNA-binding and reduced stability of enzyme
S120G
D93N
H52A
unable to complement NdK deficient Pseudomonas aeruginosa, Km values similar to wild type protein but significantly reduced turnover
H53Q
K10A
R80A
less stable than wild-type enzyme. Mutation abolishes the six intersubunit salt bridges. Compensatory stabilizing mechanisms appear for R80A mutant. The R80A mutant crystallizes into space group I222 that is unusual for nucleoside diphosphate kinases, and its hexameric structure reveals the occurrence at the trimer interface of a stabilizing hydrophobic patch around the mutation. The Tm-value of the mutant enzyme is 69.0°C, compared to 76.1°C for the wild-type enzyme
R80N
Y50F
unable to complement NdK deficient Pseudomonas aeruginosa, no phosphotransfer activity
D93N
-
less stable than wild-type enzyme. The Tm-value of the mutant enzyme is 48.4°C, compared to 76.1°C for the wild-type enzyme
-
R80A
-
less stable than wild-type enzyme. Mutation abolishes the six intersubunit salt bridges. Compensatory stabilizing mechanisms appear for R80A mutant. The R80A mutant crystallizes into space group I222 that is unusual for nucleoside diphosphate kinases, and its hexameric structure reveals the occurrence at the trimer interface of a stabilizing hydrophobic patch around the mutation. The Tm-value of the mutant enzyme is 69.0°C, compared to 76.1°C for the wild-type enzyme
-
R80N
-
less stable than wild-type enzyme. Mutation abolishes the six intersubunit salt bridges. The Tm-value of the mutant enzyme is 69.3 °C, compared to 76.1°C for the wild-type enzyme
-
H52A
Mycobacterium tuberculosis H37Ra / ATCC 25177
-
unable to complement NdK deficient Pseudomonas aeruginosa, Km values similar to wild type protein but significantly reduced turnover
-
H53Q
Mycobacterium tuberculosis H37Ra / ATCC 25177
-
unable to complement NdK deficient Pseudomonas aeruginosa, Km values similar to wild type protein but significantly reduced turnover
-
Y50F
Mycobacterium tuberculosis H37Ra / ATCC 25177
-
unable to complement NdK deficient Pseudomonas aeruginosa, no phosphotransfer activity
-
D93N
-
the mutation dramatically decreases protein thermal stability (Tm value of 43.4°C) but is still hexameric and retains full activity. The mutant hexamer is stable and active up to 2.5 M guanidine hydrochloride
-
H117Q
P72H
-
mutant strain is hypersensitive to oxidative and heat stress and shows a decrease in the levels of catalase isoforms Cat-1 and Cat-3 induced by stress and illumination. Catalase Cat-1 interacts with nucleoside diphosphate kinase
A117D
-
complete loss of nucleoside diphosphate kinase activity, but no loss of nuclease activity
A77T
site-directed mutagenesis, the mutant shows an altered import behaviour into chloroplasts compared to the wild-type enzyme, overview
E205K
the mutation of isoform NDPK2 is associated with paraquat resistance
I12L
the mutation of isoform NDPK2 is associated with paraquat resistance
P45S
the mutation of isoform NDPK3 is associated with paraquat resistance
R63D
site-directed mutagenesis, the mutant shows an altered import behaviour into chloroplasts compared to the wild-type enzyme, overview
R74D
site-directed mutagenesis, the mutant shows an altered import behaviour into chloroplasts compared to the wild-type enzyme, overview
S69A
D135A/E136T
A134E
-
site-directed mutagenesis, the mutant forms a dimer in analogy to the wild-type enzyme of Halomonas sp., which possesses an E134 residue, overview
A134E/A135E
-
site-directed mutagenesis, the mutant shows decreased oligomerization compared to the wild-type enzyme
H266L
-
generation of a Gbeta1gamma2-dimer carrying a single amino acid exchange at the intermediately phosphorylated His266 in the beta1 subunit, the mutant is termed Gbeta1H266Lgamma2, the mutant is integrated into heterotrimeric G proteins in rat cardiomyocytes but is deficient in intermediate Gbeta phosphorylation, mutant overexpression suppresses basal cAMP formation as well as the basal contractility up to 50-55% compared to the wild-type enzyme, overview
K56E/R58E
-
site-directed mutation of the residues required for membrane phospholipid binding, the NDKB mutant is defective in anionic phospholipid binding
H117N
site-directed mutagenesis, the mutant His117N fused with GFP is inactive
P95S
site-directed mutagenesis, mutation in Pro95 and in the C-terminus destabilize the hexamer fused with GFP
H117N
-
site-directed mutagenesis, the mutant His117N fused with GFP is inactive
-
P95S
-
site-directed mutagenesis, mutation in Pro95 and in the C-terminus destabilize the hexamer fused with GFP
-
additional information
H197C
no enzymatic activity, stimulates GTPase activites of Pra2 and Pra3, EC 3.6.5.2, in the same manner as wild-type NDPK2
L225stop
increased enzymatic activity, stimulates GTPase activites of Pra2 and Pra3, EC 3.6.5.2, in the same manner as wild-type NDPK2
P175S
stimulates GTPase activites of Pra2 and Pra3, EC 3.6.5.2, with a slight reduction compared to wild-type NDPK2
R230stop
increased enzymatic activity, stimulates GTPase activites of Pra2 and Pra3, EC 3.6.5.2, in the same manner as wild-type NDPK2
C139S
site-directed mutagenesis, the mutation in the dimeric nucleoside diphosphate kinase generates a catalytically competent enzyme monomer. Substitution of Cys139 for Ser causes dissociation of dimeric CsNDK into monomer in Tris buffer, and the mutant CsNDK becomes more susceptible to endproteinase GluC cleavage, which is suppressed by an NDK substrate, ATP
C139S
-
site-directed mutagenesis, the mutation in the dimeric nucleoside diphosphate kinase generates a catalytically competent enzyme monomer. Substitution of Cys139 for Ser causes dissociation of dimeric CsNDK into monomer in Tris buffer, and the mutant CsNDK becomes more susceptible to endproteinase GluC cleavage, which is suppressed by an NDK substrate, ATP
-
G114D
-
the mutant, which forms a dimer in low salt solution, is strongly stabilized by His-tag to form a stable hexamer and shows strongly reduced specific activity compared to the wild type enzyme
G114D
inactive mutant enzyme, dissociates more than wild-type enzyme in low salt buffer
G114R
wild-type enzyme is a hexamer at 25°C and dissociates to dimer at 35°C in low salt medium. Mutant maintains hexameric structure at both 25 and 35°C. Refolding of heat-denatured wild-type enzyme requires salt concentrations above 2 M. Mutant G114R efficiently refolds in presence of 1 M NaCl. Residue 114 is in close proximity to E155 of the neighboring subunit in the enzyme hexamer. In the mutant, R114 may stabilize the hexameric subunit assembly
G114R
random mutagenesis, the mutant enzyme shows increased thermal stability and refolding after salt treatment compared to the wild-type enzyme, substrate specificity and kinetic of the mutant enzyme, overview
G114R
once folded, the mutant enzyme is stable even in low salt buffer
E134A
site-directed mutagenesis, the mutant forms a tetramer in analogy to the wild-type enzyme of Pseudomonas sp., which possesses an A134 residue, overview
E134A
the mutant forms a tetramer and shows 119% specific activity compared to the wild type enzyme
S120G
naturally mutation occuring in neuroblastoma, the mutant has a folding defect, the urea-denatured protein cannot refold in vitro
D93N
the mutation dramatically decreases protein thermal stability (Tm value of 43.4°C) but is still hexameric and retains full activity. The mutant hexamer is stable and active up to 2.5 M guanidine hydrochloride
D93N
-
site-directed mutagenesis, the mutation breaks the intersubunit salt bridge Arg80-Asp93 which contributes to the thermal stability of the hexamer. The mutant thermal stability dramatically decreases by 27.6°C to 48.4°C, compared to 76°C for the wild-type enzyme
D93N
less stable than wild-type enzyme. The Tm-value of the mutant enzyme is 48.4°C, compared to 76.1°C for the wild-type enzyme
H53Q
unable to complement NdK deficient Pseudomonas aeruginosa, Km values similar to wild type protein but significantly reduced turnover
R80N
-
site-directed mutagenesis, the mutation affects the intersubunit salt bridge Arg80-Asp93 which contributes to the thermal stability of the hexamer. The mutant thermal stability dramatically decreases by 8.0°C to 68°C, compared to 76°C for the wild-type enzyme. In mutant R80N, the salt bridge is replaced by intersubunit hydrogen bonds that contribute to the thermal stability of the hexamer
R80N
less stable than wild-type enzyme. Mutation abolishes the six intersubunit salt bridges. The Tm-value of the mutant enzyme is 69.3 °C, compared to 76.1°C for the wild-type enzyme
H117Q
-
the mutation abolishes the ATPase and GTPase activities of the recombinant enzyme in vitro to almost 4.75- and 2fold, respectively. The mutation also reduces the autophosphorylation activity, almost 5fold
H117Q
Mycolicibacterium smegmatis mc(2)155 / ATCC 700084
-
the mutation abolishes the ATPase and GTPase activities of the recombinant enzyme in vitro to almost 4.75- and 2fold, respectively. The mutation also reduces the autophosphorylation activity, almost 5fold
-
S69A
6% and 14% of wild type activity using dCDP or dTDP as substrate respectively, changes in subunit composition with increasing number of tetramers and dimers
S69A
-
complete loss of nucleoside diphosphate kinase activity, but no loss of nuclease activity
additional information
-
construction of a C-terminally truncated mutant, truncation of the C-terminal arginine-threonine-arginine (RTR) residues leads to the instability of the tertiary structure resulting in reduced kinase activity compared to wild-type, mutant crystal structure analysis
additional information
-
a ndpk2 knockout mutant shows increased salt stress sensitivity compared to the wild-type enzyme. The sos2-2/ndpk2 double mutant is more salt sensitive than a sos2-2 single mutant, and does not hyperaccumulate H2O2 in response to salt stress
additional information
-
NDPK3a induction by sugars is reduced in AtWrky4 and AtWrky34 knockout mutants, Wrky4 and Wrky34 are transcription factor proteins involved in sugar induction and response, overview
additional information
transgenic Solanum tubersoum plants overexpressing the Arabidopsis thaliana NDPK2 isozyme show reduced sensitivity to stress caused by methyl viologen, i.e. reactive oxigen species, or salt or heat, compared to the wild-type plants, overview
additional information
construction of NDPK3 knockout and overexpression lines: in the NDPK-3 overexpressor, the enzyme activities of ascorbate peroxidase, peroxiredoxin, catalase, as well as superoxide dismutase are all increased compared to wild-type, in the NDPK-3 knockout line, these enzymes have reduced activity compared to wild-type. Proteomic analysis of mutants, overview
additional information
-
construction of NDPK3 knockout and overexpression lines: in the NDPK-3 overexpressor, the enzyme activities of ascorbate peroxidase, peroxiredoxin, catalase, as well as superoxide dismutase are all increased compared to wild-type, in the NDPK-3 knockout line, these enzymes have reduced activity compared to wild-type. Proteomic analysis of mutants, overview
-
additional information
-
antisense knockdown of nucleoside diphosphate kinase, the stable mutant Mtb Ndk-AS displays attenuated intracellular survival along with reduced persistence in the lungs of infected mice. In the generated mutant strain Mtb Ndk-AS the Ndk protein expression is undetectable. ROS production is inhibited in the presence of Mtb Ndk
additional information
construction of CAT-1 and NDK-1 double mutants, cat-1/ndk-1-1 and cat-1/ndk-1-2, by crossing single mutants of cat-1RIP and ndk-1P72H, which are catalytically inactive, overview
additional information
-
construction of CAT-1 and NDK-1 double mutants, cat-1/ndk-1-1 and cat-1/ndk-1-2, by crossing single mutants of cat-1RIP and ndk-1P72H, which are catalytically inactive, overview
additional information
-
transgenic plants bearing gene for enzyme antisense RNA, inhibition of cell elongation process
additional information
-
immobiliztaion of the purified recombinant enzyme on N-hydroxysuccinimide HS-activated HP resin
additional information
the Pyrobaculum aerophilum NDP kinase sequence contains two unique segments not present in other NDP kinases, comprising residues 66100 and 156165. Deletion mutants of the NDP kinase lacking either or both of these inserts have an altered substrate specificity, allowing dGTP as the phosphate donor. A structural analysis of the evolved NDP kinase in conjunction with mutagenesis experiments suggests that the substrate specificity of the enzyme is related to the presence of these two inserts
additional information
-
the Pyrobaculum aerophilum NDP kinase sequence contains two unique segments not present in other NDP kinases, comprising residues 66100 and 156165. Deletion mutants of the NDP kinase lacking either or both of these inserts have an altered substrate specificity, allowing dGTP as the phosphate donor. A structural analysis of the evolved NDP kinase in conjunction with mutagenesis experiments suggests that the substrate specificity of the enzyme is related to the presence of these two inserts
additional information
-
the Pyrobaculum aerophilum NDP kinase sequence contains two unique segments not present in other NDP kinases, comprising residues 66100 and 156165. Deletion mutants of the NDP kinase lacking either or both of these inserts have an altered substrate specificity, allowing dGTP as the phosphate donor. A structural analysis of the evolved NDP kinase in conjunction with mutagenesis experiments suggests that the substrate specificity of the enzyme is related to the presence of these two inserts
-
additional information
-
construction of chimeric mutants of NDP kinase alpha and NDP kinase beta, i.e. NDP kinase alpha1-130beta131-152 and NDP kinase beta1-130alpha131-152
