Information on EC 2.7.1.145 - deoxynucleoside kinase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.7.1.145
-
RECOMMENDED NAME
GeneOntology No.
deoxynucleoside kinase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + 2'-deoxynucleoside = ADP + 2'-deoxynucleoside 5'-phosphate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
purine deoxyribonucleosides salvage
-
-
pyrimidine deoxyribonucleosides salvage
-
-
purine metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:deoxynucleoside 5'-phosphotransferase
The enzyme from embryonic cells of the fruit fly Drosophila melanogaster differs from other 2'-deoxyribonucleoside kinases [EC 2.7.1.76 (deoxyadenosine kinase) and EC 2.7.1.113 (deoxyguanosine kinase)] in its broad specificity for all four common 2'-deoxyribonucleosides.
CAS REGISTRY NUMBER
COMMENTARY hide
52227-81-3
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
putative
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(E)-5-(2-bromovinyl)-2'-deoxyuridine + ATP
(E)-5-(2-bromovinyl)-2'-deoxyuridine 5'-phosphate + ADP
show the reaction diagram
1-beta-D-arabinofuranosylcytosine + ATP
1-beta-D-arabinofuranosylcytosine 5'-phosphate + ADP
show the reaction diagram
1-beta-D-arabinofuranosylthymine + ATP
1-beta-D-arabinofuranosylthymine 5'-phosphate + ADP
show the reaction diagram
2',3'-didehydro-3'-deoxythymidine + ATP
2',3'-didehydro-3'-deoxythymidine 5'-phosphate + ADP
show the reaction diagram
-
-
-
-
?
2',3'-dideoxyadenosine + ATP
2',3'-dideoxyadenosine 5'-phosphate + ADP
show the reaction diagram
-
0.9% of the activity with thymidine
-
-
?
2',3'-dideoxycytidine + ATP
2',3'-dideoxycytidine 5'-phosphate + ADP
show the reaction diagram
2',3'-dideoxythymidine + ATP
2',3'-dideoxythymidine 5'-phosphate + ADP
show the reaction diagram
-
4.44% of the activity with thymidine
-
-
?
2'-deoxy-2'-fluoroadenosine 3'-triphosphate + 2'-deoxyadenosine
2'-deoxy-2'-fluoroadenosine 3'-diphosphate + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
low activity
-
-
?
2'-deoxyadenosine + ATP
2'-deoxyadenosine 5'-phosphate + ADP
show the reaction diagram
2'-deoxycytidine + ATP
2'-deoxycytidine 5'-phosphate + ADP
show the reaction diagram
2'-deoxycytidine + CTP
2'-deoxycytidine 5'-phosphate + CDP
show the reaction diagram
-
-
-
-
?
2'-deoxyguanosine + ATP
2'-deoxyguanosine 5'-phosphate + ADP
show the reaction diagram
2'-deoxyuridine + ATP
2'-deoxyuridine 5'-phosphate + ADP
show the reaction diagram
2-chloro-2'-deoxyadenosine + ATP
2-chloro-2'-deoxyadenosine 5'-phosphate + ADP
show the reaction diagram
-
126% of the activity with thymidine
-
-
?
3'-azido-2',3'-dideoxythymidine + ATP
3'-azido-2',3'-dideoxythymidine 5'-phosphate + ADP
show the reaction diagram
3'-azidothymidine + ATP
3'-azidothymidine 5'-phosphate + ADP
show the reaction diagram
3'-fluoro-2',3'-dideoxythymidine + ATP
3'-fluoro-2',3'-dideoxythymidine 5'-phosphate + ADP
show the reaction diagram
-
0.03% of the activity with thymidine and 2'-deoxycytidine
-
-
?
5-fluoro-2'-deoxyuridine + ATP
5-fluoro-2'-deoxyuridine 5'-phosphate + ADP
show the reaction diagram
adenosine + ATP
adenosine 5'-phosphate + ADP
show the reaction diagram
-
0.82% of the activity with thymidine
-
-
?
adenosine-2'-deoxy-2'-fluoro-3'-triphosphate + 2'-deoxycytidine
adenosine-2'-deoxy-2'-fluoro-3'-diphosphate + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
low activity
-
-
?
adenosine-2'-deoxy-3'-triphosphate + 2'-deoxyadenosine
adenosine-2'-deoxy-3'-diphosphate + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
low activity
-
-
?
adenosine-2'-deoxy-3'-triphosphate + 2'-deoxycytidine
adenosine-2'-deoxy-3'-diphosphate + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
low activity
-
-
?
adenosine-3'-deoxy-2'-triphosphate + 2'-deoxyadenosine
adenosine-3'-deoxy-2'-diphosphate + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
low activity
-
-
?
adenosine-3'-deoxy-2'-triphosphate + 2'-deoxycytidine
adenosine-3'-deoxy-2'-diphosphate + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
low activity
-
-
?
adenosine-3'-deoxy-3'-fluoro-2'-triphosphate + 2'-deoxycytidine
adenosine-3'-deoxy-3'-fluoro-2'-diphosphate + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
low activity
-
-
?
ATP + (E)-5-(2-bromovinyl)-2'-deoxyuridine
ADP + (E)-5-(2-bromovinyl)-2'-deoxyuridine 5'-phosphate
show the reaction diagram
high activity
-
-
?
ATP + 1-(beta-D-arabinofuranosyl)-cytosine
ADP + 1-(beta-D-arabinofuranosyl)-cytosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 1-(beta-D-arabinofuranosyl)-thymine
ADP + 1-(beta-D-arabinofuranosyl)-thymine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 1-beta-D-arabinofuranosylcytosine
ADP + 1-beta-D-arabinofuranosylcytosine 5'-phosphate
show the reaction diagram
ATP + 1-beta-D-arabinofuranosylguanine
ADP + 1-beta-D-arabinofuranosylguanine 5'-phosphate
show the reaction diagram
-
poor substrate for the wild-type enzyme but moderate activity with N-terminally truncated mutants M88R and V84A/M88R
-
-
?
ATP + 1-beta-D-arabinofuranosylthymine
ADP + 1-beta-D-arabinofuranosylthymine 5'-phosphate
show the reaction diagram
ATP + 2',2'-difluorodeoxycytidine
ADP + 2',2'-difluorodeoxycytidine 5'-phosphate
show the reaction diagram
ATP + 2',2'-difluorodeoxyguanosine
ADP + 2',2'-difluorodeoxyguanosine 5'-phosphate
show the reaction diagram
-
poor substrate for the wild-type enzyme but moderate activity with N-terminally truncated mutants M88R and V84A/M88R
-
-
?
ATP + 2',3'-didehydro-3'-deoxythymidine
ADP + 2',3'-didehydro-3'-deoxythymidine 5'-phosphate
show the reaction diagram
ATP + 2',3'-dideoxycytidine
ADP + 2',3'-dideoxycytidine 5'-phosphate
show the reaction diagram
ATP + 2',3'-dideoxythymidine
ADP + 2',3'-dideoxythymidine 5'-phosphate
show the reaction diagram
ATP + 2'-deoxy-2',2'-difluorocytidine
ADP + difluorodeoxycytidine 5'-phosphate
show the reaction diagram
-
2'-deoxy-2',2'-difluorocytidine is gemcitabine, dNK is an activator of gemcitabine
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
ATP + 2'-deoxyinosine
ADP + 2'-deoxyinosine 5'-phosphate
show the reaction diagram
-
-
-
?
ATP + 2'-deoxynucleoside
ADP + 2'-deoxynucleoside 5'-phosphate
show the reaction diagram
ATP + 2'-deoxyribonucleoside
ADP + 2'-deoxyribonucleoside 5'-phosphate
show the reaction diagram
ATP + 2'-deoxythymidine
ADP + 2'-deoxythymidine 5'-phosphate
show the reaction diagram
ATP + 2'-deoxyurimidine
ADP + 2'-deoxyurimidine 5'-phosphate
show the reaction diagram
-
-
-
?
ATP + 2-chloro-2'-deoxyadenosine
ADP + 2-chloro-2'-deoxyadenosine 5'-phosphate
show the reaction diagram
ATP + 2-chlorodeoxyadenosine
ADP + 2-chlorodeoxyadenosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 2-hydroxy-2'-deoxyadenosine
ADP + 2-hydroxy-2'-deoxyadenosine 5'-monophosphate
show the reaction diagram
-
preferred substrate for enzyme mutant 4
-
-
?
ATP + 3'-azido-2',3'-didehydro-3'-deoxythymidine
ADP + 3'-azido-2',3'-didehydro-3'-deoxythymidine 5'-phosphate
show the reaction diagram
ATP + 3'-deoxyadenosine
ADP + 3'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
-
-
?
ATP + 5-(E)-(2-bromvinyl)-2'-deoxyuridine
ADP + 5-(E)-(2-bromvinyl)-2'-deoxyuridine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 5-fluoro-2'-deoxyuridine
ADP + 5-fluoro-2'-deoxyuridine 5'-phosphate
show the reaction diagram
ATP + 9-beta-D-arabinofuranosyladenine
ADP + 9-beta-D-arabinofuranosyladenine 5'-phosphate
show the reaction diagram
ATP + aciclovir
ADP + aciclovir phosphate
show the reaction diagram
ATP + adenosine
ADP + adenosine 5'-phosphate
show the reaction diagram
low activity
-
-
?
ATP + arabinosyl-2-fluoroadenine
ADP + arabinosyl-2-fluoroadenine 5'-monophosphate
show the reaction diagram
-
-
-
?
ATP + arabinosyladenine
ADP + arabinosyladenine 5'-monophosphate
show the reaction diagram
-
-
-
?
ATP + arabinosyluridine
ADP + arabinosyluridine 5'-monophosphate
show the reaction diagram
-
-
-
?
ATP + cytidine
ADP + cytidine 5'-phosphate
show the reaction diagram
ATP + deoxyuridine
ADP + deoxyuridine 5'-phosphate
show the reaction diagram
ATP + dideoxycytidine
ADP + dideoxycytidine 5'-phosphate
show the reaction diagram
-
wild-type enzyme: low activity
-
-
?
ATP + E-5-(2-bromovinyl)-2'-deoxyuridine
ADP + E-5-(2-bromovinyl)-2'-deoxyuridine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + E-5-(2-bromovinyl)-2'-deoxyuridine
ADP + E-5-(2-bromovinyl)-2'-deoxyuridine phosphate
show the reaction diagram
ATP + fludarabine
ADP + fludarabine phosphate
show the reaction diagram
-
-
-
?
ATP + ganciclovir
ADP + ganciclovir phosphate
show the reaction diagram
-
poor substrate for the wild-type enzyme but moderate activity with N-terminally truncated mutants M88R and V84A/M88R
-
-
?
ATP + guanosine
ADP + guanosine 5'-phosphate
show the reaction diagram
low activity
-
-
?
ATP + inosine
ADP + inosine 5'-phosphate
show the reaction diagram
very low activity
-
-
?
ATP + stavudine
ADP + stavudine phosphate
show the reaction diagram
ATP + thymidine
ADP + thymidine 5'-phosphate
show the reaction diagram
ATP + uridine
ADP + uridine 5'-phosphate
show the reaction diagram
bromovinyldeoxyuridine + ATP
bromovinyldeoxyuridine 5'-phosphate + ADP
show the reaction diagram
-
specificity constant 930 per s and M
-
-
?
cytidine + ATP
cytidine 5'-phosphate + ADP
show the reaction diagram
-
16% of the activity with thymidine
-
-
?
difluorodeoxycytidine + ATP
difluorodeoxycytidine 5'-phosphate + ADP
show the reaction diagram
-
i.e. gemcitabine. Efficient in vivo phosphorylation, specificity constant 4800 per s and M
-
-
?
guanosine + ATP
guanosine 5'-phosphate + ADP
show the reaction diagram
-
1.18% of the activity with thymidine
-
-
?
thymidine + ATP
thymidine 5'-phosphate + ADP
show the reaction diagram
thymidine + CTP
thymidine 5'-phosphate + CDP
show the reaction diagram
-
-
-
-
?
uridine + ATP
uridine 5'-phosphate + ADP
show the reaction diagram
-
6.45% of the activity with thymidine
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
ATP + 2'-deoxynucleoside
ADP + 2'-deoxynucleoside 5'-phosphate
show the reaction diagram
-
-
-
-
ir
ATP + 2'-deoxyribonucleoside
ADP + 2'-deoxyribonucleoside 5'-phosphate
show the reaction diagram
ATP + 2'-deoxythymidine
ADP + 2'-deoxythymidine 5'-phosphate
show the reaction diagram
thymidine + ATP
thymidine 5'-phosphate + ADP
show the reaction diagram
-
-
-
-
-
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2'-deoxy-2'-fluoroadenosine 3'-triphosphate
-
0.2-0.6% of the activity with ATP, dependent on the nucleoside substrate
adenosine-2'-deoxy-3'-triphosphate
-
0.5-1% of the activity with ATP, dependent on the nucleoside substrate
adenosine-3'-deoxy-2'-triphosphate
-
6-10% of the activity with ATP, dependent on the nucleoside substrate
-
adenosine-3'-deoxy-3'-fluoro-2'-triphosphate
-
0.2% of the activity with ATP and 2'deoxycytidine, no activity with 2'-deoxyadenosine
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(E)-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil
-
IC50: 0.0277 mM for reaction with thymidine and 0.0158 mM for reaction with 2'-deoxycytidine
(E)-5-(2-bromovinyl)-2'-deoxyuridine
(E)-5-(2-bromovinyl)-2'-deoxyuridine 5'-monophosphate
-
IC50: 0.0026 mM, reaction with thymidine, fusion protein with glutathione S-transferase
(E)-5-(2-bromovinyl)-2'-deoxyuridine 5'-triphosphate
-
IC50: 0.0069 mM, reaction with thymidine, fusion protein with glutathione S-transferase. The inhibitor is efficiently metabolized to its 5'-mono-, 5'-di- and 5'-triphosphate derivatives in the insect cell culture and abundently incorporated into the insect cell DNA
1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodouracil
-
IC50: 0.0163 mM for reaction with thymidine and 0.0154 mM for reaction with 2'-deoxycytidine
1-beta-D-arabinofuranosylcytosine
-
IC50: 0.0534 mM for reaction with thymidine and 0.089 mM for reaction with 2'-deoxycytidine
1-beta-D-arabinofuranosylthymidine
-
IC50: 0.0648 mM for reaction with thymidine and 0.0348 mM for reaction with 2'-deoxycytidine
1-beta-D-arabinofuranosyluracil
-
IC50: 0.057 mM for reaction with thymidine and 0.058 mM for reaction with 2'-deoxycytidine
2',2'-difluorodeoxycytidine
-
IC50: 0.145 mM for reaction with thymidine and 0.102 mM for reaction with 2'-deoxycytidine
2',3'-dehydro-3'-deoxythymidine
-
IC50 for reaction with thymidine is greater than 1000 mM, IC50 for reaction with 2'-deoxycytidine is 0.805 mM
2',3'-dideoxycytidine
-
IC50: 0.76 mM for reaction with thymidine and 0.838 mM for reaction with 2'-deoxycytidine
2',3'-dideoxythymidine
-
IC50: 0.075 mM for reaction with thymidine and 0.0703 mM for reaction with 2'-deoxycytidine
2'-deoxy-3'-thiacytidine
-
IC50: 0.74 mM for reaction with thymidine and 0.868 mM for reaction with 2'-deoxycytidine
2'-deoxyadenosine
-
reaction with thymidine or 2'-deoxyguanosine
2'-deoxycytidine
-
competitive with thymidine
2'-deoxyguanosine
2'-deoxyuridine
-
reaction with thymidine and 2'-deoxycytidine
2-chloro-2'-deoxyadenosine
-
IC50: 0.123 mM for reaction with thymidine and 0.12 mM for reaction with 2'-deoxycytidine
3'-azido-2',3'-dideoxythymidine
-
IC50: 0.0419 mM for reaction with thymidine and 0.0296 mM for reaction with 2'-deoxycytidine
5-fluoro-2'-deoxyuridine
-
IC50: 0.0258 mM for reaction with thymidine and 0.02235 mM for reaction with 2'-deoxycytidine
dCTP
competitive versus ATP, feedback inhibition
diphosphate
-
competitive versus ATP
thymidine
Triphosphate
-
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0045
(E)-5-(2-bromovinyl)-2'-deoxyuridine
-
37C, fusion protein with glutathione S-transferase
0.0243 - 1.441
1-(beta-D-arabinofuranosyl)-cytosine
0.062 - 0.357
1-(beta-D-arabinofuranosyl)-thymine
0.028
1-beta-D-arabinofuranosylcytosine
-
-
1.093 - 1.124
2',3'-dideoxycytidine
0.0207
2'-deoxy-2',2'-difluorocytidine
-
-
0.0181 - 3.82
2'-deoxyadenosine
0.0009 - 2.162
2'-deoxycytidine
0.0095 - 20.35
2'-deoxyguanosine
0.0009 - 5.02
2'-deoxythymidine
0.0111 - 0.0117
3'-azido-2',3'-didehydro-3'-deoxythymidine
0.0072 - 0.0083
3'-azido-2',3'-dideoxythymidine
0.0022 - 0.0049
5-(E)-(2-bromvinyl)-2'-deoxyuridine
0.0014 - 0.0025
ATP
0.292 - 1.124
Dideoxycytidine
0.92 - 5.06
ganciclovir
0.0009 - 6.56
thymidine
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0029 - 2.1
1-(beta-D-arabinofuranosyl)-cytosine
0.0003 - 1
1-(beta-D-arabinofuranosyl)-thymine
0.54 - 4.2
2',3'-dideoxycytidine
6.5
2'-deoxy-2',2'-difluorocytidine
Drosophila melanogaster
-
-
0.021 - 20.6
2'-deoxyadenosine
0.00071 - 16.5
2'-deoxycytidine
0.019 - 19
2'-deoxyguanosine
0.00072 - 5.4
2'-deoxythymidine
0.03 - 0.037
3'-azido-2',3'-didehydro-3'-deoxythymidine
0.036 - 0.052
3'-azido-2',3'-dideoxythymidine
0.0059 - 0.4
5-(E)-(2-bromvinyl)-2'-deoxyuridine
0.93 - 4.2
Dideoxycytidine
0.034 - 15
thymidine
additional information
additional information
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
314
2'-deoxy-2',2'-difluorocytidine
Drosophila melanogaster
-
-
40092
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00066
(E)-5-(2-bromovinyl)-2'-deoxyuridine
-
pH 7.6, 30C, reaction with thymidine, fusion protein with glutathione S-transferase
0.02 - 0.16
2'-deoxyadenosine
0.001
2'-deoxycytidine
-
pH 8.0, 22C, competitive with thymidine
0.1 - 0.4
2'-deoxyguanosine
0.08
diphosphate
-
versus ATP, with substrate 2'-deoxycytidine
0.0047 - 0.829
dTTP
0.001 - 0.003
thymidine
0.143
Triphosphate
-
versus ATP, with substrate 2'-deoxycytidine
0.005
TTP
-
pH 8.0, 22C
additional information
additional information
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0277
(E)-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil
Drosophila melanogaster
-
IC50: 0.0277 mM for reaction with thymidine and 0.0158 mM for reaction with 2'-deoxycytidine
0.00257
(E)-5-(2-bromovinyl)-2'-deoxyuridine
Drosophila melanogaster
-
IC50: 0.00257 mM for reaction with thymidine and 0.00194 mM for reaction with 2'-deoxycytidine
0.0026
(E)-5-(2-bromovinyl)-2'-deoxyuridine 5'-monophosphate
Drosophila melanogaster
-
IC50: 0.0026 mM, reaction with thymidine, fusion protein with glutathione S-transferase
0.0069
(E)-5-(2-bromovinyl)-2'-deoxyuridine 5'-triphosphate
Drosophila melanogaster
-
IC50: 0.0069 mM, reaction with thymidine, fusion protein with glutathione S-transferase. The inhibitor is efficiently metabolized to its 5'-mono-, 5'-di- and 5'-triphosphate derivatives in the insect cell culture and abundently incorporated into the insec
0.0163
1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodouracil
Drosophila melanogaster
-
IC50: 0.0163 mM for reaction with thymidine and 0.0154 mM for reaction with 2'-deoxycytidine
0.0534
1-beta-D-arabinofuranosylcytosine
Drosophila melanogaster
-
IC50: 0.0534 mM for reaction with thymidine and 0.089 mM for reaction with 2'-deoxycytidine
0.0648
1-beta-D-arabinofuranosylthymidine
Drosophila melanogaster
-
IC50: 0.0648 mM for reaction with thymidine and 0.0348 mM for reaction with 2'-deoxycytidine
0.057
1-beta-D-arabinofuranosyluracil
Drosophila melanogaster
-
IC50: 0.057 mM for reaction with thymidine and 0.058 mM for reaction with 2'-deoxycytidine
0.145
2',2'-difluorodeoxycytidine
Drosophila melanogaster
-
IC50: 0.145 mM for reaction with thymidine and 0.102 mM for reaction with 2'-deoxycytidine
0.805 - 1
2',3'-dehydro-3'-deoxythymidine
0.76
2',3'-dideoxycytidine
Drosophila melanogaster
-
IC50: 0.76 mM for reaction with thymidine and 0.838 mM for reaction with 2'-deoxycytidine
0.075
2',3'-dideoxythymidine
Drosophila melanogaster
-
IC50: 0.075 mM for reaction with thymidine and 0.0703 mM for reaction with 2'-deoxycytidine
0.74
2'-deoxy-3'-thiacytidine
Drosophila melanogaster
-
IC50: 0.74 mM for reaction with thymidine and 0.868 mM for reaction with 2'-deoxycytidine
0.123
2-chloro-2'-deoxyadenosine
Drosophila melanogaster
-
IC50: 0.123 mM for reaction with thymidine and 0.12 mM for reaction with 2'-deoxycytidine
0.0419
3'-azido-2',3'-dideoxythymidine
Drosophila melanogaster
-
IC50: 0.0419 mM for reaction with thymidine and 0.0296 mM for reaction with 2'-deoxycytidine
0.0258
5-fluoro-2'-deoxyuridine
Drosophila melanogaster
-
IC50: 0.0258 mM for reaction with thymidine and 0.02235 mM for reaction with 2'-deoxycytidine
0.012
dTTP
Drosophila melanogaster
-
IC50: 0.012 mM, reaction with thymidine, fusion protein with glutathione S-transferase
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.35
-
C-terminal truncated enzyme rDm-dNKDELTAC30
2.7
-
substrates 2'-deoxyadenosine and ATP
3
-
substrates 2'-deoxycytidine and ATP
23.8
-
C-terminal truncated enzyme rDm-dNKDELTAC10
36.5
-
recombinant enzyme
51.6
-
C-terminal truncated enzyme rDm-dNKDELTAC20
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
26300
2 * 26300, recombinant enzyme, SDS-PAGE
26900
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2 * 29100, recombinant full length enzyme, SDS-PAGE, 2 * 26900, recombinant N-terminally truncated enzyme, SDS-PAGE
29100
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2 * 29100, recombinant full length enzyme, SDS-PAGE, 2 * 26900, recombinant N-terminally truncated enzyme, SDS-PAGE
31300
2 * 31300, recombinant enzyme, SDS-PAGE
33000
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gel filtration
44600
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recombinant N-terminally truncated enzyme, gel filtration
46000
recombinant enzyme, native PAGE
48500
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recombinant full length enzyme, gel filtration
49000
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recombinant N-terminally truncated enzyme, native PAGE
49800
recombinant enzyme, gel filtration
57700
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recombinant full length enzyme, native PAGE
60000
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x * 60000, about, recombinant wild-type and mutant GFP-fusion protein, SDS-PAGE
64400
recombinant enzyme, gel filtration
69300
recombinant enzyme, native PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
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x * 60000, about, recombinant wild-type and mutant GFP-fusion protein, SDS-PAGE
monomer
additional information
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystal structure determination, PDB IDs 1OE0, 1OT3, 1J90, 1ZM7, 1ZMX, 2JCS, 2VP0, 2VP2, 2VP4, 2VP, 2VP6, 2VP9, 2VPP, 2VQ, and 2JJ8
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crystals of a C-terminally truncated (D20) recombinant Dm-dNK mutant E52D are grown using the vapour diffusion method by hanging drop geometry. The E52D mutant is crystallized with its feedback inhibitor dTTP. The backbone conformation remains unchanged, and coordination between D52 and the dTTPMg complex is observed
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in complex with floxuridine, brivudine, zidovudine, zalcitabine, or dCTP or dGTP with resolution of 2.2-2.9 A. dCTP and dGTP bind with the base in the substrate site, similarly to feedback inhibitor dTTP. Contrary to nucleoside analogs, dGTP adopts a syn conformation
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purified recombinant enzyme in complex with dT and dTPP, hanging drop vapour diffusion method, enzyme solution containing 5-10 mg/ml protein, 5 mM dT or dTTP, is mixed in equal volumes with cyrstallization solution containing 0.1 M MES, pH 6.5, 0.2 M ammonium sulfate, 18-22% w/v PEG 5000 monomethylether, and 5-10% w/v PEG 400, 3-5 days, 14C, X-ray diffraction structure determination and analysis at 2.4-2.5 A resolution
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purified recombinant enzyme, hanging drop vapour diffusion method, enzyme solution containing 10 mg/ml protein and 10 mM deoxycytidine, mixed with an equal volume of cyrstallization solution containing 0.1 M MES, pH 6.5, 0.2 M ammonium sulfate, 20% w/v PEG 5000, and 8-10% v/v PEG 400, X-ray diffraction structure determination and analysis at 2.6 A resolution, molecular replacement method
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purified recombinant mutant N64D in complex with dT or dTTP, counter diffusion and vapour diffusion methods, 20 mg/ml enzyme with 10 mM dT, is mixed with cyrstallization solution containing 0.15 M MES, pH 6.5, 0.3 M lithium sulfate, and 27,5% w/v PEG 2000 monomethylether, or 10 mg/ml enzyme with 5 mM dTTP is mixed with 0.1 M MES, pH 6.5, 0.16 M lithium sulfate, and 25% v/v PEG 2000 monomethylether, 2 weeks, 15C, X-ray diffraction structure determination and analysis at 3.1 A and 2.2 A resolution, respectively
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truncated dNK lacking the last 20 amino acid residues in complex with gemcitabine, hanging drop vapor diffusion method, using 0.1 M MES pH 6.5, 0.2 M lithium sulfate and 26% (w/v) mPEG2000
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
ATP stabilizes the enzyme structure
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
native enzyme from cell lines in a 5-step procedure, recombinant GST-fusion enzyme from Escherichia coli strain KY895 by GST-affinity chromatography
recombinant C-terminally His8-tagged enzyme from Escherichia coli strain BL21 by nickel affinity chromatography
recombinant C-terminally His8-tagged enzyme from Escherichia coli strain BL21 by nickel affinity chromatography, the His-tag is cleaved off by thrombin
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recombinant C-terminally His8-tagged wild-type and mutant enzymes from Escherichia coli strain BL21 by nickel affinity chromatography
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recombinant enzyme
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recombinant full length and N-terminally truncated His-tagged enzymes, the His-tags are cleaved off
recombinant His10-tagged enzyme from Spodoptera frugiperda SF9 cells by nickel affinity chromatography and gel filtration
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recombinant wild-type and mutant enzymes as glutathione-S-transferase fusion proteins from Escherichia coli by glutathione affinity chromatography
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recombinant wild-type and mutant GST-fusion enzymes from Escherichia coli by glutathione affinity chromatography
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
deoxynucleoside kinase gene is introduced into HeLa cells with cationic lipids, to allow its transient expression. Cytotoxicities of 1-beta-D-arabinofuranosylcytosine, 5-fluorodeoxyuridine, and 1-(2-deoxy-2-methylene-beta-D-erythro-pentofuranosyl)cytosine are increased by the deoxynucleoside kinase gene. The combination of the transient expression of the Drosophila deoxynucleoside kinase gene and these nucleoside analogs is a candidate for suicide gene therapy
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DNA and amino acid sequence determination and analysis, gene is located on chromosome 3 at position 91D-91E, expression of wild-type and mutant enzymes in Escherichia coli TK-deficient strain KY895
DNA and amino acid sequence determination and analysis, overexpression in TK-deficient Escherichia coli strain KY895 as GST-fusion protein
DNA and amino acid sequence determination and analysis, phylogenetic analysis, expression as C-terminally His8-tagged protein in Escherichia coli strain BL21
DNA and amino acid sequence determination and analysis, phylogenetic analysis, expression as full length and N-terminally truncated His-tagged enzymes in Escherichia coli
DNA and amino acid sequence determination and analysis, phylogenetic analysis, expression of wild-type and as C-terminally His8-tagged protein in Escherichia coli strain BL21
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expressed in Escherichia coli K-12 cells
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expression in a thymidine kinase 1-deficient osteosarcoma cell line. Mitochondrial targeting of Dm-dNK facilitates nucleoside and nucleoside analog phosphorylation and could be used as a strategy to enhance the efficacy of nucleoside analog phosphorylation and concomitantly their cytostatic potential; expression in osteosarcoma cell line
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expression in Escherichia coli
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expression in Escherichia coli; wild-type and truncated enzyme forms with removal of 10, 20 or 30 C-terminal amino acids, expression as a fusion protein with glutathione S-transferase
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expression in HeLa cells from replicating plasmid, using pYK-CMV-luc, pCMV-dNK-T, and pCMV-dNK, is highly cytotoxic and causes cell death without help of nucleoside analogues. Caspase 3/7 activities are not enhanced by transfection of the Dm-dNK gene on a replicating plasmid
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expression of the wild-type and mutant enzymes in enzyme-deficient Escherichia coli strain KY895
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expression of wild-type and mutant enzymes as glutathione-S-transferase fusion proteins in Escherichia coli
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expression of wild-type and mutant enzymes in Escherichia coli as GST-fusion proteins
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expression of wild-type and mutant enzymes in Escherichia coli strain BL21 as C-terminally His8-tagged proteins
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gemcitabine resistance due to deoxycytidine kinase deficiency can be reverted by fruitfly deoxynucleoside kinase, DmdNK, in human uterine sarcoma cells
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gene dnk, isolated from a phage library, DNA and amino acid sequence determination and analysis, recombinant expression of randomly mutated genes for deoxyribonucleoside kinase in Escherichia coli strain BL21, recombinant expression of catalytically active His10-tagged mutant 4 enzyme in Spodoptera frugiperda SF9 cells
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heterologous expression of Drosophila melanogaster enzyme Dm-dNK increases the sensitivity of cancer cells to several cytotoxic nucleoside analogues, recombinant expression of GFP-tagged mutant and wild-type enzymes in TK-1-deficient osteosarcoma cells. dThd kinase activities increased about 40fold in the cells expressing the nuclear dNK-GFP and about 35fold in the cells expressing the mitochondrial mito-dNK-GFP, compared with the untransduced parent cells
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overexpression of wild-type and mutant enzyme fused to GFP in cancer cell lines in the nucleus and cytosol, respectively
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upon expression in Escherichia coli, enzyme sensitizes cells against various nucleic acid analogs such as gemcitabine
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wild-type and mutant enzymes, expression in Escherichia coli
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A110D
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site-directed mutagenesis, altered substrate specificity and kinetics, and highly reduced activity compared to the wild-type enzyme
E52D
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markedly decreased kcat
E52H
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markedly decreased kcat
E52Q
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inactive mutant protein
F114A
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site-directed mutagenesis, active site mutant, altered substrate specificity compared to the wild-type enzyme
F114Y
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site-directed mutagenesis, active site mutant, altered substrate specificity compared to the wild-type enzyme
I102M/N117S/M118V/D208N
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clones harbouring the mutant enzyme are more sensitive to 3'-azido-2',3'-dideoxythymidine and beta-D-arabinofuranosylcytosine
I29H
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site-directed mutagenesis, active site mutant, altered substrate specificity compared to the wild-type enzyme
I29H/F114Y
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site-directed mutagenesis, active site mutant, inactive mutant
I47T/N210D
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clones harbouring the mutant enzyme are more sensitive to 3'-azido-2',3'-dideoxythymidine and beta-D-arabinofuranosylcytosine
M1T/T85A/N121S
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clones harbouring the mutant enzyme are more sensitive to 1-beta-D-arabinofuranosylcytosine and 2',3'-dideoxycytidine
M88R/A110D
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site-directed mutagenesis, altered substrate specificity and kinetics, and highly reduced activity compared to the wild-type enzyme
N210D/L239P
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clones harbouring the mutant enzyme are more sensitive to 3'-azido-2',3'-dideoxythymidine and beta-D-arabinofuranosylcytosine
N28P
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site-directed mutagenesis, active site mutant, inactive mutant
N28P/I29H
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site-directed mutagenesis, active site mutant, inactive mutant
N28P/I29H/F114Y
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site-directed mutagenesis, active site mutant, inactive mutant
N38D/N64D
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clones harbouring the mutant enzyme are more sensitive specifically to 3'-azido-2',3'-dideoxythymidine
N45D
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site-directed mutagenesis, decreased activity with natural substrates
N45D/N64D
N59D/M118V/Y179H
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clones harbouring the mutant enzyme are more sensitive to 3'-azido-2',3'-dideoxythymidine and beta-D-arabinofuranosylcytosine
N64D
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site-directed mutagenesis, highly decreased activity with natural substrates, decreased feedback inhibition by dTTP compared to the wild-type enzyme
N64S/L68S/M69L
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clones harbouring the mutant enzyme are more sensitive specifically to 3'-azido-2',3'-dideoxythymidine
Q81D
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site-directed mutagenesis, active site mutant, inactive mutant
R105H
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markedly decreased kcat
R105K
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inactive mutant protein
R247S
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site-directed mutagenesis, mutation abolishes nuclear import of the enzyme, the mutant enzyme is localized in the cytosol
T12A/V84A/N213S
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clones harbouring the mutant enzyme are more sensitive to 1-beta-D-arabinofuranosylcytosine
T85A
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clones harbouring the mutant enzyme are more sensitive to 1-beta-D-arabinofuranosylcytosine and 2',3'-dideoxycytidine
V84A/M88R
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site-directed mutagenesis of the full length enzyme and of the DELTA20 N-terminally truncated enzyme, highly increased Km for acceptor substrates, altered substrate specificity compared to the wild-type enzyme
V84A/M88R/A110D
V84M
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site-directed mutagenesis, altered substrate specificity and kinetics, and highly reduced activity compared to the wild-type enzyme
V84S
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site-directed mutagenesis, altered substrate specificity and kinetics, and reduced activity compared to the wild-type enzyme
V84S/M88R/A110D
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site-directed mutagenesis, altered substrate specificity and kinetics, and highly reduced activity compared to the wild-type enzyme
Y70W
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mutant enzyme loses activity towards purines. Negative cooperativity towards dThd and dCyd is observed
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
agriculture
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multifunctional deoxynucleoside kinase of insect cells is a target for development of new highly selective insecticidial drugs
medicine
synthesis
additional information
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DmdNK broad substrate specificity and fast turnover rate make it an interesting candidate for suicide gene therapy, as well as in numerous biotechnological applications