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Information on EC 2.7.1.145 - deoxynucleoside kinase and Organism(s) Drosophila melanogaster and UniProt Accession Q9XZT6
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2.7.1.145 deoxynucleoside kinaseIUBMB Comments
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.
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Word Map
- 2.7.1.145
- thymidine
- drosophila
- deoxycytidine
-
suicide
- deoxyguanosine
-
herpes
- medicine
- deoxyadenosine
-
e-5-2-bromovinyl-2'-deoxyuridine
-
kinase-deficient
- dttp
- deoxythymidine
-
dado
- 1-beta-d-arabinofuranosylthymine
- synthesis
- agriculture
The taxonomic range for the selected organisms is: Drosophila melanogaster
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
dm-dnk, deoxyribonucleoside kinase, deoxynucleoside kinase, multisubstrate deoxyribonucleoside kinase, pyrimidine deoxyribonucleoside kinase, dmdnk, deoxyribonucleoside phosphotransferase, xen-pyk, multi-substrate deoxyribonucleoside kinase, d. melanogaster deoxynucleoside kinase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
dNK
-
nucleoside triphosphate: deoxyribonucleoside 5'-phosphotransferase
-
D. melanogaster deoxynucleoside kinase
-
-
-
-
deoxyribonucleoside kinase
-
-
-
-
deoxyribonucleoside phosphotransferase
-
-
-
-
Dm-dNK
dNK
kinase (phosphorylating), deoxynucleoside
-
-
-
-
ms-dNK
-
-
-
-
multifunctional deoxynucleoside kinase
-
-
-
-
multispecific deoxynucleoside kinase
-
-
-
-
multisubstrate deoxyribonucleoside kinase
additional information
Dm-dNK
-
-
-
-
dNK
-
-
-
-
dNK
-
-
multisubstrate deoxyribonucleoside kinase
-
-
-
-
multisubstrate deoxyribonucleoside kinase
-
-
additional information
the enzyme belongs to the thymidine kinase 2-like, i.e. TK2-like, family of enzymes
additional information
the enzyme belongs to the thymidine kinase 2-like, i.e. TK2-like, family of enzymes
additional information
-
the enzyme belongs to the thymidine kinase 2-like, i.e. TK2-like, family of enzymes
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + a 2'-deoxyribonucleoside = ADP + a 2'-deoxyribonucleoside 5'-phosphate
compulsory ordered steady-state reaction mechanism with formation of a ternary complex with the phosphate donor and acceptor
-
ATP + a 2'-deoxyribonucleoside = ADP + a 2'-deoxyribonucleoside 5'-phosphate
straight forward hyperbolic kinetic reaction mechanism following a compulsory ordered steady-state reaction mechanism with formation of a ternary complex, substrate interactions
ATP + a 2'-deoxyribonucleoside = ADP + a 2'-deoxyribonucleoside 5'-phosphate
substrate binding and interactions
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
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
52227-81-3
-
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
(E)-5-(2-bromovinyl)-2'-deoxyuridine + ATP
(E)-5-(2-bromovinyl)-2'-deoxyuridine 5'-phosphate + ADP
54% of the activity with thymidine
-
-
?
1-beta-D-arabinofuranosylcytosine + ATP
1-beta-D-arabinofuranosylcytosine 5'-phosphate + ADP
58.2% of the activity with thymidine
-
-
?
1-beta-D-arabinofuranosylthymine + ATP
1-beta-D-arabinofuranosylthymine 5'-phosphate + ADP
53.9% of the activity with thymidine
-
-
?
2',3'-dideoxyadenosine + ATP
2',3'-dideoxyadenosine 5'-phosphate + ADP
0.9% of the activity with thymidine
-
-
?
2',3'-dideoxycytidine + ATP
2',3'-dideoxycytidine 5'-phosphate + ADP
11.1% of the activity with thymidine
-
-
?
2',3'-dideoxythymidine + ATP
2',3'-dideoxythymidine 5'-phosphate + ADP
4.44% of the activity with thymidine
-
-
?
2'-deoxyadenosine + ATP
2'-deoxyadenosine 5'-phosphate + ADP
96% of the activity with thymidine
-
-
?
2'-deoxyguanosine + ATP
2'-deoxyguanosine 5'-phosphate + ADP
53% of the activity with thymidine
-
-
?
2'-deoxyuridine + ATP
2'-deoxyuridine 5'-phosphate + ADP
113% of the activity with thymidine
-
-
?
2-chloro-2'-deoxyadenosine + ATP
2-chloro-2'-deoxyadenosine 5'-phosphate + ADP
126% of the activity with thymidine
-
-
?
3'-azido-2',3'-dideoxythymidine + ATP
3'-azido-2',3'-dideoxythymidine 5'-phosphate + ADP
2% of the activity with thymidine
-
-
?
5-fluoro-2'-deoxyuridine + ATP
5-fluoro-2'-deoxyuridine 5'-phosphate + ADP
92% of the activity with thymidine
-
-
?
adenosine + ATP
adenosine 5'-phosphate + ADP
0.82% of the activity with thymidine
-
-
?
ATP + 1-beta-D-arabinofuranosylcytosine
ADP + 1-beta-D-arabinofuranosylcytosine 5'-phosphate
-
-
-
?
ATP + 1-beta-D-arabinofuranosylthymine
ADP + 1-beta-D-arabinofuranosylthymine 5'-phosphate
-
-
-
?
ATP + 2'-deoxy-2',2'-difluorocytidine
ADP + difluorodeoxycytidine 5'-phosphate
2'-deoxy-2',2'-difluorocytidine is gemcitabine, dNK is an activator of gemcitabine
-
-
?
ATP + 2'-deoxyinosine
ADP + 2'-deoxyinosine 5'-phosphate
-
-
-
?
ATP + 2-amino-8-(1'-beta-D-2'-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one
ADP + 2-amino-8-(1'-beta-D-2'-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one 5'-phosphate
-
-
-
?
ATP + 2-chloro-2'-deoxyadenosine
ADP + 2-chloro-2'-deoxyadenosine 5'-phosphate
-
-
-
?
ATP + 2-hydroxy-2'-deoxyadenosine
ADP + 2-hydroxy-2'-deoxyadenosine 5'-monophosphate
preferred substrate for enzyme mutant 4
-
-
?
ATP + 5-fluoro-2'-deoxyuridine
ADP + 5-fluoro-2'-deoxyuridine 5'-phosphate
-
-
-
?
ATP + 6-amino-5-nitro-3-(1'-beta-D-2'-deoxyribofuranosyl)-2(1H)-pyridone
ADP + 6-amino-5-nitro-3-(1'-beta-D-2'-deoxyribofuranosyl)-2(1H)-pyridone 5'-phosphate
-
-
-
?
ATP + adenosine
ADP + adenosine 5'-phosphate
low activity
-
-
?
ATP + arabinosyl-2-fluoroadenine
ADP + arabinosyl-2-fluoroadenine 5'-monophosphate
-
-
-
?
ATP + arabinosyladenine
ADP + arabinosyladenine 5'-monophosphate
-
-
-
?
ATP + arabinosyluridine
ADP + arabinosyluridine 5'-monophosphate
-
-
-
?
ATP + E-5-(2-bromovinyl)-2'-deoxyuridine
ADP + E-5-(2-bromovinyl)-2'-deoxyuridine phosphate
-
-
-
?
ATP + guanosine
ADP + guanosine 5'-phosphate
low activity
-
-
?
ATP + inosine
ADP + inosine 5'-phosphate
very low activity
-
-
?
ATP + uridine
ADP + uridine 5'-phosphate
very low activity
-
-
?
cytidine + ATP
cytidine 5'-phosphate + ADP
16% of the activity with thymidine
-
-
?
guanosine + ATP
guanosine 5'-phosphate + ADP
1.18% of the activity with thymidine
-
-
?
uridine + ATP
uridine 5'-phosphate + ADP
6.45% of the activity with thymidine
-
-
?
(E)-5-(2-bromovinyl)-2'-deoxyuridine + ATP
(E)-5-(2-bromovinyl)-2'-deoxyuridine 5'-phosphate + ADP
1-beta-D-arabinofuranosylcytosine + ATP
1-beta-D-arabinofuranosylcytosine 5'-phosphate + ADP
1-beta-D-arabinofuranosylthymine + ATP
1-beta-D-arabinofuranosylthymine 5'-phosphate + ADP
2',3'-didehydro-3'-deoxythymidine + ATP
2',3'-didehydro-3'-deoxythymidine 5'-phosphate + ADP
-
-
-
-
?
2',3'-dideoxyadenosine + ATP
2',3'-dideoxyadenosine 5'-phosphate + ADP
-
0.9% of the activity with thymidine
-
-
?
2'-deoxy-2'-fluoroadenosine 3'-triphosphate + 2'-deoxyadenosine
2'-deoxy-2'-fluoroadenosine 3'-diphosphate + 2'-deoxyadenosine 5'-phosphate
-
low activity
-
-
?
2-chloro-2'-deoxyadenosine + ATP
2-chloro-2'-deoxyadenosine 5'-phosphate + ADP
-
126% of the activity with thymidine
-
-
?
3'-azido-2',3'-dideoxythymidine + ATP
3'-azido-2',3'-dideoxythymidine 5'-phosphate + ADP
-
-
-
-
?
3'-fluoro-2',3'-dideoxythymidine + ATP
3'-fluoro-2',3'-dideoxythymidine 5'-phosphate + ADP
-
0.03% of the activity with thymidine and 2'-deoxycytidine
-
-
?
adenosine + ATP
adenosine 5'-phosphate + ADP
-
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
-
low activity
-
-
?
adenosine-2'-deoxy-3'-triphosphate + 2'-deoxyadenosine
adenosine-2'-deoxy-3'-diphosphate + 2'-deoxyadenosine 5'-phosphate
-
low activity
-
-
?
adenosine-2'-deoxy-3'-triphosphate + 2'-deoxycytidine
adenosine-2'-deoxy-3'-diphosphate + 2'-deoxycytidine 5'-phosphate
-
low activity
-
-
?
adenosine-3'-deoxy-2'-triphosphate + 2'-deoxyadenosine
adenosine-3'-deoxy-2'-diphosphate + 2'-deoxyadenosine 5'-phosphate
-
low activity
-
-
?
adenosine-3'-deoxy-2'-triphosphate + 2'-deoxycytidine
adenosine-3'-deoxy-2'-diphosphate + 2'-deoxycytidine 5'-phosphate
-
low activity
-
-
?
adenosine-3'-deoxy-3'-fluoro-2'-triphosphate + 2'-deoxycytidine
adenosine-3'-deoxy-3'-fluoro-2'-diphosphate + 2'-deoxycytidine 5'-phosphate
-
low activity
-
-
?
ATP + 1-(beta-D-arabinofuranosyl)-cytosine
ADP + 1-(beta-D-arabinofuranosyl)-cytosine 5'-phosphate
-
-
-
-
?
ATP + 1-(beta-D-arabinofuranosyl)-thymine
ADP + 1-(beta-D-arabinofuranosyl)-thymine 5'-phosphate
-
-
-
-
?
ATP + 1-beta-D-arabinofuranosylcytosine
ADP + 1-beta-D-arabinofuranosylcytosine 5'-phosphate
-
-
-
-
?
ATP + 1-beta-D-arabinofuranosylguanine
ADP + 1-beta-D-arabinofuranosylguanine 5'-phosphate
-
poor substrate for the wild-type enzyme but moderate activity with N-terminally truncated mutants M88R and V84A/M88R
-
-
?
ATP + 2',2'-difluorodeoxyguanosine
ADP + 2',2'-difluorodeoxyguanosine 5'-phosphate
-
poor substrate for the wild-type enzyme but moderate activity with N-terminally truncated mutants M88R and V84A/M88R
-
-
?
ATP + 2-chlorodeoxyadenosine
ADP + 2-chlorodeoxyadenosine 5'-phosphate
-
-
-
-
?
ATP + 3'-azido-2',3'-didehydro-3'-deoxythymidine
ADP + 3'-azido-2',3'-didehydro-3'-deoxythymidine 5'-phosphate
-
-
-
-
?
ATP + 5-(E)-(2-bromvinyl)-2'-deoxyuridine
ADP + 5-(E)-(2-bromvinyl)-2'-deoxyuridine 5'-phosphate
-
-
-
-
?
ATP + 9-beta-D-arabinofuranosyladenine
ADP + 9-beta-D-arabinofuranosyladenine 5'-phosphate
-
poor substrate for the wild-type enzyme but moderate activity with N-terminally truncated mutants M88R and V84A/M88R
-
-
?
ATP + a 2'-deoxyribonucleoside
ADP + a 2'-deoxyribonucleoside 5'-phosphate
-
-
-
-
?
ATP + dideoxycytidine
ADP + dideoxycytidine 5'-phosphate
-
wild-type enzyme: low activity
-
-
?
ATP + E-5-(2-bromovinyl)-2'-deoxyuridine
ADP + E-5-(2-bromovinyl)-2'-deoxyuridine 5'-phosphate
-
-
-
-
?
ATP + E-5-(2-bromovinyl)-2'-deoxyuridine
ADP + E-5-(2-bromovinyl)-2'-deoxyuridine phosphate
-
-
-
-
?
ATP + ganciclovir
ADP + ganciclovir phosphate
-
poor substrate for the wild-type enzyme but moderate activity with N-terminally truncated mutants M88R and V84A/M88R
-
-
?
ATP + thymidine
ADP + thymidine 5'-phosphate
-
wild-type enzyme: preferred substrate
-
-
?
cytidine + ATP
cytidine 5'-phosphate + ADP
-
16% of the activity with thymidine
-
-
?
guanosine + ATP
guanosine 5'-phosphate + ADP
-
1.18% of the activity with thymidine
-
-
?
thymidine + ATP
thymidine 5'-phosphate + ADP
-
-
-
-
?
uridine + ATP
uridine 5'-phosphate + ADP
-
6.45% of the activity with thymidine
-
-
?
2'-deoxycytidine + ATP
2'-deoxycytidine 5'-phosphate + ADP
-
-
-
?
2'-deoxycytidine + ATP
2'-deoxycytidine 5'-phosphate + ADP
134% of the activity with thymidine
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
-
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
1% of the activity with 2'-deoxythymidine
-
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
88% of the activity with 2'-deoxythymidine
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
-
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
-
-
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
0.2% of the activity with 2'-deoxythymidine
-
-
?
ATP + 2'-deoxyribonucleoside
ADP + 2'-deoxyribonucleoside 5'-phosphate
-
-
-
?
ATP + 2'-deoxyribonucleoside
ADP + 2'-deoxyribonucleoside 5'-phosphate
-
-
-
-
?
ATP + 2'-deoxyribonucleoside
ADP + 2'-deoxyribonucleoside 5'-phosphate
-
-
-
?
ATP + 2'-deoxyribonucleoside
ADP + 2'-deoxyribonucleoside 5'-phosphate
-
-
-
-
?
ATP + 2'-deoxythymidine
ADP + 2'-deoxythymidine 5'-phosphate
-
-
-
?
ATP + 2'-deoxythymidine
ADP + 2'-deoxythymidine 5'-phosphate
-
-
-
-
?
ATP + 2'-deoxythymidine
ADP + 2'-deoxythymidine 5'-phosphate
best substrate
-
-
?
ATP + 2'-deoxythymidine
ADP + 2'-deoxythymidine 5'-phosphate
2'-deoxythymidine binding structure at the active site, overview
-
-
?
ATP + a 2'-deoxyribonucleoside
ADP + a 2'-deoxyribonucleoside 5'-phosphate
-
-
-
?
ATP + a 2'-deoxyribonucleoside
ADP + a 2'-deoxyribonucleoside 5'-phosphate
-
-
-
-
?
(E)-5-(2-bromovinyl)-2'-deoxyuridine + ATP
(E)-5-(2-bromovinyl)-2'-deoxyuridine 5'-phosphate + ADP
-
-
-
-
?
(E)-5-(2-bromovinyl)-2'-deoxyuridine + ATP
(E)-5-(2-bromovinyl)-2'-deoxyuridine 5'-phosphate + ADP
-
54% of the activity with thymidine
-
-
?
1-beta-D-arabinofuranosylcytosine + ATP
1-beta-D-arabinofuranosylcytosine 5'-phosphate + ADP
-
10% of the activity with thymidine and 2'-deoxycytidine
-
-
?
1-beta-D-arabinofuranosylcytosine + ATP
1-beta-D-arabinofuranosylcytosine 5'-phosphate + ADP
-
58.2% of the activity with thymidine
-
-
?
1-beta-D-arabinofuranosylcytosine + ATP
1-beta-D-arabinofuranosylcytosine 5'-phosphate + ADP
-
50% of the activity with thymidine and 2'-deoxycytidine
-
-
?
1-beta-D-arabinofuranosylthymine + ATP
1-beta-D-arabinofuranosylthymine 5'-phosphate + ADP
-
15% of the activity with thymidine and 2'-deoxycytidine
-
-
?
1-beta-D-arabinofuranosylthymine + ATP
1-beta-D-arabinofuranosylthymine 5'-phosphate + ADP
-
53.9% of the activity with thymidine
-
-
?
2',3'-dideoxycytidine + ATP
2',3'-dideoxycytidine 5'-phosphate + ADP
-
-
-
-
?
2',3'-dideoxycytidine + ATP
2',3'-dideoxycytidine 5'-phosphate + ADP
-
0.02% of the activity with thymidine and 2'-deoxycytidine
-
-
?
2'-deoxyadenosine + ATP
2'-deoxyadenosine 5'-phosphate + ADP
-
-
-
-
?
2'-deoxyadenosine + ATP
2'-deoxyadenosine 5'-phosphate + ADP
-
5% of the activity with thymidine and 2'-deoxycytidine
-
-
?
2'-deoxyadenosine + ATP
2'-deoxyadenosine 5'-phosphate + ADP
-
15% of the activity with thymidine and 2'-deoxycytidine
-
-
?
2'-deoxycytidine + ATP
2'-deoxycytidine 5'-phosphate + ADP
-
-
-
?
2'-deoxycytidine + ATP
2'-deoxycytidine 5'-phosphate + ADP
-
-
-
-
?
2'-deoxyguanosine + ATP
2'-deoxyguanosine 5'-phosphate + ADP
-
-
-
-
?
2'-deoxyguanosine + ATP
2'-deoxyguanosine 5'-phosphate + ADP
-
1% of the activity with thymidine and 2'-deoxycytidine
-
-
?
2'-deoxyguanosine + ATP
2'-deoxyguanosine 5'-phosphate + ADP
-
4% of the activity with thymidine and 2'-deoxycytidine
-
-
?
2'-deoxyuridine + ATP
2'-deoxyuridine 5'-phosphate + ADP
-
113% of the activity with thymidine
-
-
?
2'-deoxyuridine + ATP
2'-deoxyuridine 5'-phosphate + ADP
-
90% of the activity with thymidine and 2'-deoxycytidine
-
-
?
3'-azidothymidine + ATP
3'-azidothymidine 5'-phosphate + ADP
-
0.5% of the activity with thymidine and 2'-deoxycytidine
-
-
?
3'-azidothymidine + ATP
3'-azidothymidine 5'-phosphate + ADP
-
0.3% of the activity with thymidine and 2'-deoxycytidine
-
-
?
5-fluoro-2'-deoxyuridine + ATP
5-fluoro-2'-deoxyuridine 5'-phosphate + ADP
-
92% of the activity with thymidine
-
-
?
5-fluoro-2'-deoxyuridine + ATP
5-fluoro-2'-deoxyuridine 5'-phosphate + ADP
-
activity is 10% higher than with thymidine and 2'-deoxycytidine
-
-
?
ATP + 2',2'-difluorodeoxycytidine
ADP + 2',2'-difluorodeoxycytidine 5'-phosphate
-
-
-
-
?
ATP + 2',2'-difluorodeoxycytidine
ADP + 2',2'-difluorodeoxycytidine 5'-phosphate
-
best substrate for the N-terminally truncated mutant M88R
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
-
-
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
-
best substrate for the N-terminally truncated mutant V84A/M88R
-
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
-
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
-
wild-type enzyme: second-best substrate
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
-
-
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
-
poor substrate for the wild-type enzyme
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
-
poor substrate for the wild-type enzyme but moderate activity with N-terminally truncated mutants M88R and V84A/M88R
-
-
?
ATP + 2'-deoxynucleoside
ADP + 2'-deoxynucleoside 5'-phosphate
-
-
-
-
ir
ATP + 2'-deoxynucleoside
ADP + 2'-deoxynucleoside 5'-phosphate
-
dNK has a significant preference for pyrimidine deoxynucleosides over purine deoxynucleosides, but it does phosphorylate deoxyadenosine and deoxyguanosine at significant rates
-
-
?
ATP + 2'-deoxythymidine
ADP + 2'-deoxythymidine 5'-phosphate
-
-
-
-
?
ATP + 2'-deoxythymidine
ADP + 2'-deoxythymidine 5'-phosphate
-
best substrate for the wild-type enzyme
-
-
?
ATP + 2'-deoxythymidine
ADP + 2'-deoxythymidine 5'-phosphate
-
substrate binding structure of mutant N64D
-
-
?
additional information
?
-
the recombinant enzyme preferentially phosphorylates the pyrimidine nucleosides, but phosphorylation of the purine nucleosidesis also efficiently catalyzed
-
-
?
additional information
?
-
-
the recombinant enzyme preferentially phosphorylates the pyrimidine nucleosides, but phosphorylation of the purine nucleosidesis also efficiently catalyzed
-
-
?
additional information
?
-
enzyme shows broad substrate specificity, this enzyme specificity-type is the earliest in evolution probably encoded by the so-called dCK/dGK/TK2-like gene, several duplications of the progenitor gene are the reason for evolutionary occurring of nucleoside kinases with strict substrate specificities in other organism, phylogenetic tree, insects lost all but 1 nucleotide kinase, overview
-
-
?
additional information
?
-
enzyme shows broad substrate specificity involving V84, M88, and A110
-
-
?
additional information
?
-
the enzyme shows broad substrate specificity probably due to a wide substrate binding cleft
-
-
?
additional information
?
-
the multisubstrate kinase from Drosophila prefers pyrimidines
-
-
?
additional information
?
-
Dm-dNK phosphorylates a broad range of substrates including analogues of both purine and pyrimidine nucleosides, and exhibits a higher activity than other nucleoside kinases
-
-
?
additional information
?
-
-
Dm-dNK phosphorylates a broad range of substrates including analogues of both purine and pyrimidine nucleosides, and exhibits a higher activity than other nucleoside kinases
-
-
?
additional information
?
-
enzyme DmdNK is able to phosphorylate all four natural 2'-deoxyribonucleosides with high efficiency, it shows broad specificity and high turnover towards the naturally occurring 2'-deoxyribonucleosides and a similar broad specificity towards nucleoside analogues used in chemotherapy, substrate specificity towards natural and non-natural nucleosides, overview
-
-
?
additional information
?
-
substrate binding of non-TK1-like dNKs, overview
-
-
?
additional information
?
-
-
activity with CTP is 110% of the activity ATP
-
-
?
additional information
?
-
-
CTP has the same phosphotransfer capability as ATP
-
-
?
additional information
?
-
-
enzyme evolution by gene duplication of a progenitor kinase
-
-
?
additional information
?
-
-
amino acid residues responsible for substrate specificity are V84, M88, and A110, wild-type enzyme shows broad substrate specificity preferring pyrimidines to purines, substrate specificities of wild-type and mutant enzymes, overview
-
-
?
additional information
?
-
-
no activity with adenosine-3'-deoxy-3'-fluoroxylo-2'-triphosphate and adenosine-2'-deoxy-3'-fluoroara-3'-triphosphate as phosphate donors
-
-
?
additional information
?
-
-
no activity with diphosphate, or triphosphate as phosphate donors
-
-
?
additional information
?
-
-
substrate specificities of wild-type and mutant enzymes, overview, no or poor activity with ganciclovir
-
-
?
additional information
?
-
-
dNK plays a role in cell proliferation in physiological conditions
-
-
?
additional information
?
-
-
transient expression of Drosophila melanogaster deoxynucleoside kinase gene in HeLa cells enhances cytotoxicity of nucleoside analogs
-
-
?
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
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
-
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
-
-
-
?
ATP + 2'-deoxythymidine
ADP + 2'-deoxythymidine 5'-phosphate
-
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
-
-
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
-
-
-
-
?
ATP + 2'-deoxynucleoside
ADP + 2'-deoxynucleoside 5'-phosphate
-
-
-
-
ir
ATP + 2'-deoxythymidine
ADP + 2'-deoxythymidine 5'-phosphate
-
-
-
-
?
ATP + a 2'-deoxyribonucleoside
ADP + a 2'-deoxyribonucleoside 5'-phosphate
-
-
-
-
?
ATP + 2'-deoxyribonucleoside
ADP + 2'-deoxyribonucleoside 5'-phosphate
-
-
-
?
ATP + 2'-deoxyribonucleoside
ADP + 2'-deoxyribonucleoside 5'-phosphate
-
-
-
-
?
ATP + 2'-deoxyribonucleoside
ADP + 2'-deoxyribonucleoside 5'-phosphate
-
-
-
?
ATP + 2'-deoxyribonucleoside
ADP + 2'-deoxyribonucleoside 5'-phosphate
-
-
-
-
?
ATP + a 2'-deoxyribonucleoside
ADP + a 2'-deoxyribonucleoside 5'-phosphate
-
-
-
?
ATP + a 2'-deoxyribonucleoside
ADP + a 2'-deoxyribonucleoside 5'-phosphate
-
-
-
-
?
additional information
?
-
enzyme shows broad substrate specificity, this enzyme specificity-type is the earliest in evolution probably encoded by the so-called dCK/dGK/TK2-like gene, several duplications of the progenitor gene are the reason for evolutionary occurring of nucleoside kinases with strict substrate specificities in other organism, phylogenetic tree, insects lost all but 1 nucleotide kinase, overview
-
-
?
additional information
?
-
the multisubstrate kinase from Drosophila prefers pyrimidines
-
-
?
additional information
?
-
-
enzyme evolution by gene duplication of a progenitor kinase
-
-
?
additional information
?
-
-
dNK plays a role in cell proliferation in physiological conditions
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
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
ATP
stabilizes the enzyme structure, binding structure, Q111 and Arg118 are involved
ATP
-
cannot be substituted by with diphosphate, triphosphate, or polyphosphate as phosphate donors
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
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
IC50: 0.00257 mM for reaction with thymidine and 0.00194 mM for reaction with 2'-deoxycytidine
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-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
(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
dTTP
competitive versus ATP inpresence of 2'-deoxythymidine as substrate, feedback inhibition, mechanism, binding structure at the active site, overview
dTTP
-
IC50: 0.012 mM, reaction with thymidine, fusion protein with glutathione S-transferase
dTTP
-
competitive versus ATP, feedback inhibition, binding at the active site, binding structure of mutant N64D, modelling
thymidine
-
strong inhibitor of reaction with 2'-deoxycytidine, 2'-deoxyguanosine or 2'-deoxyadenosine
TTP
-
mutant enzyme N45D/N64D shows a decrease in feedback inhibition compared to the wild-type enzyme
additional information
no inhibition by dNTPs other than dTTP
-
additional information
-
multifunctional deoxynucleoside kinase of insect cells is a target for development of new highly selective insecticidial drugs
-
additional information
-
increased cell sensitivity to nucleoside analogues E-5-(2-bromovinyl)-2'-deoxyuridine and 1-beta-D-arabinofuranosylthymine in recombinant cancer cells overexpressing the enzyme in the nucleus or cytosol
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0217 - 0.09
2-amino-8-(1'-beta-D-2'-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one
-
0.0045
(E)-5-(2-bromovinyl)-2'-deoxyuridine
-
37°C, fusion protein with glutathione S-transferase
0.0113
2'-deoxycytidine
mutant enzyme Q81E, at pH 7.6 and 37°C
0.4307
2'-deoxyguanosine
wild type enzyme, at pH 7.6 and 37°C
1.612
2'-deoxyguanosine
mutant enzyme Q81E, at pH 7.6 and 37°C
0.0217
2-amino-8-(1'-beta-D-2'-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one
mutant enzyme Q81E, at pH 7.6 and 37°C
-
0.09
2-amino-8-(1'-beta-D-2'-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one
wild type enzyme, at pH 7.6 and 37°C
-
0.00068
6-amino-5-nitro-3-(1'-beta-D-2'-deoxyribofuranosyl)-2(1H)-pyridone
mutant enzyme Q81E, at pH 7.6 and 37°C
-
0.1017
6-amino-5-nitro-3-(1'-beta-D-2'-deoxyribofuranosyl)-2(1H)-pyridone
wild type enzyme, at pH 7.6 and 37°C
-
0.0243
1-(beta-D-arabinofuranosyl)-cytosine
-
37°C, pH 7.5, wild-type enzyme
1.441
1-(beta-D-arabinofuranosyl)-cytosine
-
37°C, pH 7.5, mutant enzyme Y70W
0.062
1-(beta-D-arabinofuranosyl)-thymine
-
37°C, pH 7.5, wild-type enzyme
0.357
1-(beta-D-arabinofuranosyl)-thymine
-
37°C, pH 7.5, mutant enzyme Y70W
0.0025
2'-deoxythymidine
-
pH 7.6, 37°C, recombinant wild-type enzyme
0.0025
2'-deoxythymidine
-
recombinant wild-type enzyme, pH 7.6, 37°C
0.1
2'-deoxythymidine
-
above, pH 7.6, 37°C, recombinant mutants I29H and Q81D
0.79
2'-deoxythymidine
-
recombinant N-terminally truncated mutant M88R, pH 7.6, 37°C
3.3
2'-deoxythymidine
-
recombinant N-terminally truncated mutant V84A/M88R, pH 7.6, 37°C
0.0111
3'-azido-2',3'-didehydro-3'-deoxythymidine
-
recombinant mutant N64D
0.0117
3'-azido-2',3'-didehydro-3'-deoxythymidine
-
recombinant mutant N45D
0.0022
5-(E)-(2-bromvinyl)-2'-deoxyuridine
-
37°C, pH 7.5, wild-type enzyme
0.0049
5-(E)-(2-bromvinyl)-2'-deoxyuridine
-
37°C, pH 7.5, mutant enzyme Y70W
1.2
ganciclovir
-
recombinant N-terminally truncated mutant M88R, pH 7.6, 37°C
1.75
ganciclovir
-
recombinant N-terminally truncated mutant V84A/M88R, pH 7.6, 37°C
additional information
additional information
straight forward hyperbolic kinetic reaction mechanism following a compulsory ordered steady-state reaction mechanism with formation of a ternary complex
-
additional information
additional information
-
Km-values of chimeric enzymes
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.817 - 1.398
2-amino-8-(1'-beta-D-2'-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one
-
0.728
2'-deoxyguanosine
mutant enzyme Q81E, at pH 7.6 and 37°C
0.817
2-amino-8-(1'-beta-D-2'-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one
wild type enzyme, at pH 7.6 and 37°C
-
1.398
2-amino-8-(1'-beta-D-2'-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one
mutant enzyme Q81E, at pH 7.6 and 37°C
-
0.00583
6-amino-5-nitro-3-(1'-beta-D-2'-deoxyribofuranosyl)-2(1H)-pyridone
wild type enzyme, at pH 7.6 and 37°C
-
0.067
6-amino-5-nitro-3-(1'-beta-D-2'-deoxyribofuranosyl)-2(1H)-pyridone
mutant enzyme Q81E, at pH 7.6 and 37°C
-
0.0029
1-(beta-D-arabinofuranosyl)-cytosine
-
37°C, pH 7.5, wild-type enzyme
2.1
1-(beta-D-arabinofuranosyl)-cytosine
-
37°C, pH 7.5, mutant enzyme Y70W
0.0003
1-(beta-D-arabinofuranosyl)-thymine
-
37°C, pH 7.5, wild-type enzyme
1
1-(beta-D-arabinofuranosyl)-thymine
-
37°C, pH 7.5, mutant enzyme Y70W
0.03
3'-azido-2',3'-didehydro-3'-deoxythymidine
-
recombinant mutant N45D
0.037
3'-azido-2',3'-didehydro-3'-deoxythymidine
-
recombinant mutant N64D
0.0059
5-(E)-(2-bromvinyl)-2'-deoxyuridine
-
37°C, pH 7.5, wild-type enzyme
0.4
5-(E)-(2-bromvinyl)-2'-deoxyuridine
-
37°C, pH 7.5, mutant enzyme Y70W
additional information
additional information
-
turnover-numbers of chimeric enzymes
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
9 - 65
2-amino-8-(1'-beta-D-2'-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one
-
183.3
2'-deoxycytidine
mutant enzyme Q81E, at pH 7.6 and 37°C
0.45
2'-deoxyguanosine
mutant enzyme Q81E, at pH 7.6 and 37°C
9
2-amino-8-(1'-beta-D-2'-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one
wild type enzyme, at pH 7.6 and 37°C
-
65
2-amino-8-(1'-beta-D-2'-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one
mutant enzyme Q81E, at pH 7.6 and 37°C
-
0.0583
6-amino-5-nitro-3-(1'-beta-D-2'-deoxyribofuranosyl)-2(1H)-pyridone
wild type enzyme, at pH 7.6 and 37°C
-
98.3
6-amino-5-nitro-3-(1'-beta-D-2'-deoxyribofuranosyl)-2(1H)-pyridone
mutant enzyme Q81E, at pH 7.6 and 37°C
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00066
(E)-5-(2-bromovinyl)-2'-deoxyuridine
-
pH 7.6, 30°C, reaction with thymidine, fusion protein with glutathione S-transferase
0.001
2'-deoxycytidine
-
pH 8.0, 22°C, competitive with thymidine
0.16
2'-deoxyadenosine
-
pH 8.0, 22°C, reaction with 2'-deoxyguanosine
0.4
2'-deoxyguanosine
-
pH 8.0, 22°C, reaction with 2'-deoxyadenosine
0.0047
dTTP
-
uncompetitive versus 2'-deoxythymidine, recombinant wild-type enzyme
0.52
dTTP
-
uncompetitive versus 2'-deoxythymidine, recombinant mutant N64D
0.001
thymidine
-
pH 8.0, 22°C, competitive with 2'-deoxycytidine
additional information
additional information
feedback inhibition kinetics
-
additional information
additional information
-
inhibition kinetics, overview
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
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
0.0163
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
0.76
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
0.0026
(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
0.012
dTTP
Drosophila melanogaster
-
IC50: 0.012 mM, reaction with thymidine, fusion protein with glutathione S-transferase
0.805
2',3'-dehydro-3'-deoxythymidine
Drosophila melanogaster
IC50 for reaction with 2'-deoxycytidine is 0.805 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
catalytic efficiencies of wild-type and mutant enzymes, overview
additional information
-
substrate specificities of wild-type and mutant enzymes
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
dNK is the only deoxyriconucleoside kinase in the fruitfly
SwissProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Dm-dNK localizes to the nucleus through a mitochondrial localization signal
Dm-dNK localizes to the nucleus through a C-terminal nuclear localization signal
-
enzyme possesses 2 potential nuclear targeting sequences
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
evolution of dNKs, overview. The two families of dNKs, the TK1-like kinases and the non-TK1-like kinases, have overall unique monomer structures and only share significant protein sequence similarity at the Ploop, a glycine rich ATP binding domain close to the N-terminus. This suggests that the two families have different evolutionary origins. The insect dNK is a non-TK1 like kinase
physiological function
physiological function
-
dNK expression increases substantially sensitivity of cells to 5-aza-2'-deoxycytidine and 2'-deoxy-zebularine
additional information
physiological function
DmdNK is cell cycle regulated and under the control of cyclin E and the dE2F1 transcription factor, involved in G1/S phase transition
physiological function
no differences between mutant cytosolic Dm-dNK, mitochondrial Dm-dNK, and wild-type nuclear Dm-dNK in regards to enzyme activity, cellular sensitivity to nucleoside analogues, or bystander cell killing. Tan IIA may influence the bystander effect of cancer cells expressing Dm-dNK by regulating the expression of Cx43 and Cx26. Tanshinone (Tan) IIA is a fat-soluble and pharmacologically active ingredient of Danshen, a traditional Chinese medicine used in the treatment of cardiovascular diseases. It is isolated from the rhizome of a Chinese herb Salvia miltiorrhiza. Tan IIA treatment of osteosarcoma cells results in the upregulation of Cx43 and Cx26 proteins
additional information
enzyme identification using a mutagenic nucleoside analogue 2-hydroxy-2'-deoxyadenosine 5'-monophosphate, overview. Method development and evaluation for in vivo evolution selection method for active deoxyribonucleoside kinase proteins, including selection of antibiotic-resistant colonies resulting frommutations by phosphorylated 2-hydroxy-deoxyadenosine and the subsequent isolation of the plasmid DNAs. Fifteen Dm-dNK mutants selected after the seventh and eighth evolutioncycles are actually active in vivo, one shows activity similar to the wild-typ enzyme
additional information
-
enzyme identification using a mutagenic nucleoside analogue 2-hydroxy-2'-deoxyadenosine 5'-monophosphate, overview. Method development and evaluation for in vivo evolution selection method for active deoxyribonucleoside kinase proteins, including selection of antibiotic-resistant colonies resulting frommutations by phosphorylated 2-hydroxy-deoxyadenosine and the subsequent isolation of the plasmid DNAs. Fifteen Dm-dNK mutants selected after the seventh and eighth evolutioncycles are actually active in vivo, one shows activity similar to the wild-typ enzyme
additional information
structure of non-TK1 like kinases, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). DNK_DROME
250
0
29088
Swiss-Prot
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
29000
26900
-
2 * 29100, recombinant full length enzyme, SDS-PAGE, 2 * 26900, recombinant N-terminally truncated enzyme, SDS-PAGE
29100
-
2 * 29100, recombinant full length enzyme, SDS-PAGE, 2 * 26900, recombinant N-terminally truncated enzyme, SDS-PAGE
30000
60000
-
x * 60000, about, recombinant wild-type and mutant GFP-fusion protein, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
?
-
x * 60000, about, recombinant wild-type and mutant GFP-fusion protein, SDS-PAGE
dimer
-
2 * 29100, recombinant full length enzyme, SDS-PAGE, 2 * 26900, recombinant N-terminally truncated enzyme, SDS-PAGE
monomer
additional information
ternary and quarternary structure analysis, overview
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
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
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, 14°C, X-ray diffraction structure determination and analysis at 2.4-2.5 A resolution
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
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
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
-
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, 15°C, X-ray diffraction structure determination and analysis at 3.1 A and 2.2 A resolution, respectively
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
N45D/N64D
site-directed mutagenesis, mutant shows increased drug sensitivity and decreased inhibition by dTTP compared to the wild-type enzyme
Q81E
the mutant enzyme shows higher phosphorylating activity with 6-amino-5-nitro-3-(1'-beta-D-2'-deoxyribofuranosyl)-2(1H)-pyridone as compared to the wild type enzyme
A110D
-
site-directed mutagenesis, altered substrate specificity and kinetics, and highly reduced activity compared to the wild-type enzyme
F114A
-
site-directed mutagenesis, active site mutant, altered substrate specificity compared to the wild-type enzyme
F114Y
-
site-directed mutagenesis, active site mutant, altered substrate specificity compared to the wild-type enzyme
I102M/N117S/M118V/D208N
-
clones harbouring the mutant enzyme are more sensitive to 3'-azido-2',3'-dideoxythymidine and beta-D-arabinofuranosylcytosine
I29H
-
site-directed mutagenesis, active site mutant, altered substrate specificity compared to the wild-type enzyme
I29H/F114Y
-
site-directed mutagenesis, active site mutant, inactive mutant
I47T/N210D
-
clones harbouring the mutant enzyme are more sensitive to 3'-azido-2',3'-dideoxythymidine and beta-D-arabinofuranosylcytosine
M1T/T85A/N121S
-
clones harbouring the mutant enzyme are more sensitive to 1-beta-D-arabinofuranosylcytosine and 2',3'-dideoxycytidine
M88R
M88R/A110D
-
site-directed mutagenesis, altered substrate specificity and kinetics, and highly reduced activity compared to the wild-type enzyme
N210D/L239P
-
clones harbouring the mutant enzyme are more sensitive to 3'-azido-2',3'-dideoxythymidine and beta-D-arabinofuranosylcytosine
N28P
-
site-directed mutagenesis, active site mutant, inactive mutant
N28P/I29H
-
site-directed mutagenesis, active site mutant, inactive mutant
N28P/I29H/F114Y
-
site-directed mutagenesis, active site mutant, inactive mutant
N38D/N64D
-
clones harbouring the mutant enzyme are more sensitive specifically to 3'-azido-2',3'-dideoxythymidine
N45D
-
site-directed mutagenesis, decreased activity with natural substrates
N45D/N64D
N59D/M118V/Y179H
-
clones harbouring the mutant enzyme are more sensitive to 3'-azido-2',3'-dideoxythymidine and beta-D-arabinofuranosylcytosine
N64D
-
site-directed mutagenesis, highly decreased activity with natural substrates, decreased feedback inhibition by dTTP compared to the wild-type enzyme
N64S/L68S/M69L
-
clones harbouring the mutant enzyme are more sensitive specifically to 3'-azido-2',3'-dideoxythymidine
Q81D
-
site-directed mutagenesis, active site mutant, inactive mutant
Q81N
R247S
-
site-directed mutagenesis, mutation abolishes nuclear import of the enzyme, the mutant enzyme is localized in the cytosol
T12A/V84A/N213S
-
clones harbouring the mutant enzyme are more sensitive to 1-beta-D-arabinofuranosylcytosine
T85A
-
clones harbouring the mutant enzyme are more sensitive to 1-beta-D-arabinofuranosylcytosine and 2',3'-dideoxycytidine
V84A
V84A/M88R
-
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
-
site-directed mutagenesis, altered substrate specificity and kinetics, and highly reduced activity compared to the wild-type enzyme
V84S
-
site-directed mutagenesis, altered substrate specificity and kinetics, and reduced activity compared to the wild-type enzyme
V84S/M88R/A110D
-
site-directed mutagenesis, altered substrate specificity and kinetics, and highly reduced activity compared to the wild-type enzyme
Y70W
-
mutant enzyme loses activity towards purines. Negative cooperativity towards dThd and dCyd is observed
additional information
M88R
-
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
M88R
-
site-directed mutagenesis, altered substrate specificity and kinetics, and highly reduced activity compared to the wild-type enzyme
N45D/N64D
-
clones harbouring the mutant enzyme are more sensitive to 3'-azido-2',3'-dideoxythymidine and other nucleoside analogs
N45D/N64D
-
mutant enzyme with the largest und universal increase in sensitivity of all mutants tested. 316fold increase to 3'-azido-2',3'-dideoxythymidine, more than 11fold to 2',3'-dideoxycytidine, and 3.2fold increase in sensitivity to beta-D-arabinofuranosylcytosine and 2',3'-dideoxyadenosine. Higher Km-values for native substrates than wild-type enzyme and Vmax-values are substantially lower, decrease in feedback inhibition by TTP, Km and Vmax values for 3'-azido-2',3'-dideoxythymidine and Km value for 2',3'-dideoxycytidine are nearly unchanged
N45D/N64D
-
decreased activity with natural substrates, decreased feedback inhibition by dTTP compared to the wild-type enzyme
N45D/N64D
-
enhanced cytotoxicity for parimidine analogs especially azidothymidine
Q81N
-
site-directed mutagenesis, active site mutant, altered substrate specificity compared to the wild-type enzyme
Q81N
-
mutation shows a 200fold and 100fold increase in Km. kcat is decreased 5fold and 2fold for dThd and dCyd
V84A
-
clones harbouring the mutant enzyme are more sensitive to 1-beta-D-arabinofuranosylcytosine
V84A
-
site-directed mutagenesis, altered substrate specificity and kinetics, and reduced activity compared to the wild-type enzyme
V84A/M88R/A110D
-
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
-
site-directed mutagenesis, altered substrate specificity and kinetics, and highly reduced activity compared to the wild-type enzyme
additional information
the deletion mutants rDm-dNKDELTAC10 and rDm-dNKDELTAC20 show the same substrate activity pattern as the recombinant wild-type enzyme. Relative phosphorylation of 2'-deoxycytidine and 2-chloro-2'-deoxyadenosine increases with increasing C-terminal truncation. The relative activities of rDm-dNKDELTAC10 and rDm-dNKDELTAC20 with deoxyribonucleosides remains largely unchanged, whereas there is a substantial decrease in the phosphorylation of the purine ribonucleosides adenosine and guanosine, as well as of all dideoxyribonucleosides and 3'-azido-2',3'-dideoxythymidine. The relative activities with the pyrimidine ribonucleosides and 1-beta-D-arabinofuranosylcytosine and 1-beta-D-arabinofuranosylthymine are not affected by the C-terminal deletions
additional information
-
the deletion mutants rDm-dNKDELTAC10 and rDm-dNKDELTAC20 show the same substrate activity pattern as the recombinant wild-type enzyme. Relative phosphorylation of 2'-deoxycytidine and 2-chloro-2'-deoxyadenosine increases with increasing C-terminal truncation. The relative activities of rDm-dNKDELTAC10 and rDm-dNKDELTAC20 with deoxyribonucleosides remains largely unchanged, whereas there is a substantial decrease in the phosphorylation of the purine ribonucleosides adenosine and guanosine, as well as of all dideoxyribonucleosides and 3'-azido-2',3'-dideoxythymidine. The relative activities with the pyrimidine ribonucleosides and 1-beta-D-arabinofuranosylcytosine and 1-beta-D-arabinofuranosylthymine are not affected by the C-terminal deletions
additional information
enzyme DmdNK is adsorbed on a solid ion exchange support (bearing primary amino groups) achieving an expressed activity of over 98%. Upon cross-linking with aldehyde dextran, the expressed activity is 30-40%, both biocatalysts (adsorbed or cross-linked) are stable at pH 10.0 and room temperature for 24 h with about 70% of retained activity. Optimization of the reaction conditions to 50 mM ammonium acetate, a substrate/ATP ratio of 1:1.25, 2 mM MgCl2, 37°C, pH 8.0, results in conversions of up to 90%
additional information
-
expression of the enzyme in enzyme-deficient Escherichia coli strain KY895 confers resistnce against 3'-azido-2',3'-didehydro-3'-deoxythymidine at more than 0.1 mM
additional information
-
overexpression in cancer cell lines leads to increased cell sensitivity to several cytotoxic nucleoside analogues, expression of wild-type and mutant enzyme in an osteosarcoma cell line utilizing a replication-deficient retroviral vector reveals that the localization of the enzyme in cytosol or nucleus is not important for cell sensitivity and bystander cell killing
additional information
-
construction of libraries of hybrid enzymes by non-homologous recombination of the pyrimidinespecific human thymidine kinase 2 and the broad-specificity dNK from Drosophila melanogaster. Identification of chimeras that phosphorylate nucleoside analogs with higher activity than either parental enzyme, and that possess new activity towards the anti-HIV prodrug 2',3'-didehydro-3'-deoxythymidine
additional information
-
creation of mutants with increased specificity for several nucleoside analogs. The mutants have a reduced ability to phosphorylate pyrimidines, while the ability to phosphorylate purine analogs is relatively similar to the wild-type enzyme
additional information
-
engineering of multisubstrate nucleoside kinase targeted to the mitochondrial matrix and expression in thymidine kinase-1 deficient osteosarcoma cell line. Although the total deoxythymidine phosphorylation activity is similar in cells expressing multisubstrate nullceoside kinase in the nucleus or in the mitochondria, the cells expressing the enzyme in the mitochondria show higher sensitivity to the antiproliferative activity of pyrimidine nucleoside analogs, such as (E)-5-(2-bromovinyl)-2-deoxyuridine, 5-bromo-2-deoxyuridine, and 5-fluoro-2-deoxyuridine. Cells expressing the mitochondrial enzyme have an increased incorporation of [3H]dThd into DNA, due to a higher [3H]dTTP specific activity of the total dTTP pool in the cells in which the enzyme is targeted to the mitochondria
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
chelating Sepharose column chromatography and Superdex S200 gel filtration
recombinant His10-tagged enzyme from Spodoptera frugiperda SF9 cells by nickel affinity chromatography and gel filtration
recombinant C-terminally His8-tagged enzyme from Escherichia coli strain BL21 by nickel affinity chromatography, the His-tag is cleaved off by thrombin
-
recombinant C-terminally His8-tagged wild-type and mutant enzymes from Escherichia coli strain BL21 by nickel affinity chromatography
-
recombinant wild-type and mutant enzymes as glutathione-S-transferase fusion proteins from Escherichia coli by glutathione affinity chromatography
-
recombinant wild-type and mutant GST-fusion enzymes from Escherichia coli by glutathione affinity chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
expression in Escherichia coli
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
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
the enzyme with a deletion of the last 20 amino acid residues is expressed in MCF-7-R cells
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
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
-
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
-
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 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
-
expression of the wild-type and mutant enzymes in enzyme-deficient Escherichia coli strain KY895
-
expression of wild-type and mutant enzymes as glutathione-S-transferase fusion proteins in Escherichia coli
-
expression of wild-type and mutant enzymes in Escherichia coli as GST-fusion proteins
-
expression of wild-type and mutant enzymes in Escherichia coli strain BL21 as C-terminally His8-tagged proteins
-
gemcitabine resistance due to deoxycytidine kinase deficiency can be reverted by fruitfly deoxynucleoside kinase, DmdNK, in human uterine sarcoma cells
-
overexpression of wild-type and mutant enzyme fused to GFP in cancer cell lines in the nucleus and cytosol, respectively
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
synthesis
agriculture
-
multifunctional deoxynucleoside kinase of insect cells is a target for development of new highly selective insecticidial drugs
medicine
additional information
DmdNK broad substrate specificity and fast turnover rate make it an interesting candidate for suicide gene therapy, as well as in numerous biotechnological applications
medicine
enzyme with increased specificity towards certain analogues can be used as a suicide gene in combined gene/chemotherapy treatment of cancer
medicine
the enzyme activates a number of medically important nucleoside analogues
medicine
possible use of this enzyme as a suicide gene in vitro and in vivo
medicine
suicide gene dmdnk in several cancer cell lines, overview. In vivo testing in a xenograft model for breast cancer, both wild-type DmdNK and mutants of DmdNK are combined with gemcitabine (dFdC, 2',2'-difluoro-deoxycytidine) as the NA prodrug and a positive effect of decreasing tumor volume and increased survival time
medicine
lentivirusx1emediated Drosophila melanogaster deoxyribonucleoside kinase combined with (E)-5-(2-bromovinyl)-2'-deoxyuridine or 1-beta-D-arabinofuranosylthymine therapy may be effective in treating keloid fibroblasts
medicine
the recombinant enzyme is used to sensitize human cancer cell lines to gemcitabine
synthesis
enzyme can be utilized in industrial large-scale production of dNTPs and analogues, used for DNA synthetic reactions, giving a higher yield and less toxic byproducts compared to chemical processes
synthesis
the cross-linked DmdNK preparation is used for the preparative synthesis of arabinosyladenine monophosphate (ara-AMP) and fludarabine monophosphate (FaraAMP)
medicine
-
the enzyme can be used as a suicide gene in combined gene/chemotherapy treatment of cancer
medicine
-
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
medicine
-
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
medicine
-
transduced deoxyribonucleoside kinases can be used to kill recipient cells in combination with nucleoside prodrugs
medicine
-
mitochondrial targeting of multisubstrate nucleoside kinase 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
medicine
-
the enzyme is a potential candidate for reversing acquired gemcitabine resistance in triplex1enegative breast cancer cells, which may form the basis of strategies for the treatment of patients with drugx1eresistant triplex1enegative breast cancer
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Munch-Petersen, B.; Piskur, J.; Sondergaard, L.
The single deoxynucleoside kinase in Drosophila melanogaster, Dm-dNK, is multifunctional and differs from the mammalian deoxynucleoside kinases
Adv. Exp. Med. Biol.
431
465-469
1998
Drosophila melanogaster, Drosophila melanogaster S-2
Munch-Petersen, B.; Piskur, J.; Sondergaard, L.
Four deoxynucleoside kinase activities from Drosophila melanogaster are contained within a single monomeric enzyme, a new multifunctional deoxynucleoside kinase
J. Biol. Chem.
273
3926-3931
1998
Drosophila melanogaster, Drosophila melanogaster S-2
Johansson, M.; van Rompay, A.R.; Degreve, B.; Balzarini, J.; Karlsson, A.
Cloning and characterization of the multisubstrate deoxyribonucleoside kinase of Drosophila melanogaster
J. Biol. Chem.
274
23814-23819
1999
Drosophila melanogaster (Q9XZT6), Drosophila melanogaster
Munch-Petersen, B.; Knecht, W.; Lenz, C.; Sondergaard, L.; Piskur, J.
Functional expression of a multisubstrate deoxyribonucleoside kinase from Drosophila melanogaster and its C-terminal deletion mutants
J. Biol. Chem.
275
6673-6679
2000
Drosophila melanogaster (Q9XZT6), Drosophila melanogaster
Balzarini, J.; Degreve, B.; Hatse, S.; De Clercq, E.; Breuer, M.; Johansson, M.; Huybrechts, R.; Karlsson, A.
The multifunctional deoxynucleoside kinase of insect cells is a target for the development of new insecticides
Mol. Pharmacol.
57
811-819
2000
Drosophila melanogaster
Knecht, W.; Munch-Petersen, B.; Piskur, J.
Identification of residues involved in the specificity and regulation of the highly efficient multisubstrate deoxyribonucleoside kinase from Drosophila melanogaster
J. Mol. Biol.
301
827-837
2000
Drosophila melanogaster
Zheng, X.; Johansson, M.; Karlsson, A.
Nucleoside analog cytotoxicity and bystander cell killing of cancer cells expressing Drosophila melanogaster deoxyribonucleoside kinase in the nucleus or cytosol
Biochem. Biophys. Res. Commun.
289
229-233
2001
Drosophila melanogaster
Krawiec, K.; Kierdaszuk, B.; Shugar, D.
Inorganic tripolyphosphate (PPP(i)) as a phosphate donor for human deoxyribonucleoside kinases
Biochem. Biophys. Res. Commun.
301
192-197
2003
Drosophila melanogaster
Mikkelsen, N.E.; Johansson, K.; Karlsson, A.; Knecht, W.; Andersen, G.; Piskur, J.; Munch-Petersen, B.; Eklund, H.
Structural basis for feedback inhibition of the deoxyribonucleoside salvage pathway: studies of the Drosophila deoxyribonucleoside kinase
Biochemistry
42
5706-5712
2003
Drosophila melanogaster (Q9XZT6)
Eriksson, S.; Munch-Petersen, B.; Johansson, K.; Eklund, H.
Structure and function of cellular deoxyribonucleoside kinases
Cell. Mol. Life Sci.
59
1327-1346
2002
Bombyx mori, Drosophila melanogaster (Q9XZT6)
Knecht, W.; Sandrini, M.P.; Johansson, K.; Eklund, H.; Munch-Petersen, B.; Piskur, J.
A few amino acid substitutions can convert deoxyribonucleoside kinase specificity from pyrimidines to purines
Embo J.
21
1873-1880
2002
Drosophila melanogaster
Solaroli, N.; Bjerke, M.; Amiri, M.H.; Johansson, M.; Karlsson, A.
Active site mutants of Drosophila melanogaster multisubstrate deoxyribonucleoside kinase
Eur. J. Biochem.
270
2879-2884
2003
Drosophila melanogaster
Welin, M.; Skovgaard, T.; Knecht, W.; Zhu, C.; Berenstein, D.; Munch-Petersen, B.; Piskur, J.; Eklund, H.
Structural basis for the changed substrate specificity of Drosophila melanogaster deoxyribonucleoside kinase mutant N64D
FEBS J.
272
3733-3742
2005
Drosophila melanogaster
Piskur, J.; Sandrini, M.P.B.; Knecht, W.; Munch-Petersen, B.
Animal deoxyribonucleoside kinases: 'forward' and 'retrograde' evolution of their substrate specificity
FEBS Lett.
560
3-6
2004
Drosophila melanogaster (Q9XZT6)
Knecht, W.; Petersen, G.E.; Munch-Petersen, B.; Piskur, J.
Deoxyribonucleoside kinases belonging to the thymidine kinase 2 (TK2)-like group vary significantly in substrate specificity, kinetics and feed-back regulation
J. Mol. Biol.
315
529-540
2002
Drosophila melanogaster, Xenopus laevis (Q8UVZ9), Xenopus laevis, Bombyx mori (Q9BKL3), Bombyx mori
Johansson, K.; Ramaswamy, S.; Ljungcrantz, C.; Knecht, W.; Piskur, J.; Munch-Petersen, B.; Eriksson, S.; Eklund, H.
Structural basis for substrate specificities of cellular deoxyribonucleoside kinases
Nat. Struct. Biol.
8
616-620
2001
Drosophila melanogaster (Q9XZT6)
Krawiec, K.; Kierdaszuk, B.; Kalinichenko, E.N.; Rubinova, E.B.; Mikhailopulo, I.A.; Eriksson, S.; Munch-Petersen, B.; Shugar, D.
Ability of adenosine-2'(3')-deoxy-3'(2')-triphosphates and related analogues to replace ATP as phosphate donor for all human and Drosphila melanogaster deoxyribonucleoside kinases
Nucleosides Nucleotides Nucleic Acids
22
1525-1529
2003
Drosophila melanogaster
Solaroli, N.; Bjerke, M.; Johansson, M.; Karlsson, A.
Investigation of the substrate recognition of Drosophila melanogaster nucleoside kinase by site directed mutagenesis
Nucleosides Nucleotides Nucleic Acids
23
1527-1529
2004
Drosophila melanogaster
Jordheim, L.P.; Galmarini, C.M.; Dumontet, C.
Gemcitabine resistance due to deoxycytidine kinase deficiency can be reverted by fruitfly deoxynucleoside kinase, DmdNK, in human uterine sarcoma cells
Cancer Chemother. Pharmacol.
58
547-554
2006
Drosophila melanogaster
Legent, K.; Mas, M.; Dutriaux, A.; Bertrandy, S.; Flagiello, D.; Delanoue, R.; Piskur, J.; Silber, J.
In vivo analysis of Drosophila deoxyribonucleoside kinase function in cell cycle, cell survival and anti-cancer drugs resistance
Cell Cycle
5
740-749
2006
Drosophila melanogaster
Egeblad-Welin, L.; Sonntag, Y.; Eklund, H.; Munch-Petersen, B.
Functional studies of active-site mutants from Drosophila melanogaster deoxyribonucleoside kinase. Investigations of the putative catalytic glutamate-arginine pair and of residues responsible for substrate specificity
FEBS J.
274
1542-1551
2007
Drosophila melanogaster
Knecht, W.; Rozpedowska, E.; Le Breton, C.; Willer, M.; Gojkovic, Z.; Sandrini, M.P.; Joergensen, T.; Hasholt, L.; Munch-Petersen, B.; Piskur, J.
Drosophila deoxyribonucleoside kinase mutants with enhanced ability to phosphorylate purine analogs
Gene Ther.
14
1278-1286
2007
Drosophila melanogaster
Gerth, M.L.; Lutz, S.
Non-homologous recombination of deoxyribonucleoside kinases from human and Drosophila melanogaster yields human-like enzymes with novel activities
J. Mol. Biol.
370
742-751
2007
Drosophila melanogaster
Solaroli, N.; Zheng, X.; Johansson, M.; Balzarini, J.; Karlsson, A.
Mitochondrial expression of the Drosophila melanogaster multisubstrate deoxyribonucleoside kinase
Mol. Pharmacol.
72
1593-1598
2007
Drosophila melanogaster
Kamiya, H.; Ochiai, H.; Harashima, H.; Ito, M.; Matsuda, A.
Transient expression of Drosophila melanogaster deoxynucleoside kinase gene enhances cytotoxicity of nucleoside analogs
Nucleosides Nucleotides Nucleic Acids
25
553-560
2006
Drosophila melanogaster
Mikkelsen, N.E.; Munch-Petersen, B.; Eklund, H.
Structural studies of nucleoside analog and feedback inhibitor binding to Drosophila melanogaster multisubstrate deoxyribonucleoside kinase
FEBS J.
275
2151-2160
2008
Drosophila melanogaster (Q9XZT6), Drosophila melanogaster
Knecht, W.; Mikkelsen, N.E.; Clausen, A.R.; Willer, M.; Eklund, H.; Gojkovic, Z.; Piskur, J.
Drosophila melanogaster deoxyribonucleoside kinase activates gemcitabine
Biochem. Biophys. Res. Commun.
382
430-433
2009
Drosophila melanogaster (Q9XZT6), Drosophila melanogaster
Betham, B.; Shalhout, S.; Marquez, V.E.; Bhagwat, A.S.
Use of Drosophila deoxynucleoside kinase to study mechanism of toxicity and mutagenicity of deoxycytidine analogs in Escherichia coli
DNA Repair
9
153-160
2010
Drosophila melanogaster
Ito, M.; Suda, Y.; Harashima, H.; Kamiya, H.
Cytotoxic effect of Drosophila deoxynucleoside kinase gene on replicating plasmid in HeLa cells
Biol. Pharm. Bull.
33
1223-1227
2010
Drosophila melanogaster
Serra, I.; Conti, S.; Piškur, J.; Clausen, A.; Munch-Petersen, B.; Terreni, M.; Ubiali, D.
Immobilized Drosophila melanogaster deoxyribonucleoside kinase (DmdNK) as a high performing biocatalyst for the synthesis of purine arabinonucleotides
Adv. Synth. Catal.
356
563-570
2014
Drosophila melanogaster (Q9XZT6)
-
Kamiya, H.; Ito, M.; Nishi, K.; Harashima, H.
In vivo selection of active deoxyribonucleoside kinase by a mutagenic nucleoside analog
J. Biotechnol.
228
52-57
2016
Drosophila melanogaster (Q9XZT6), Drosophila melanogaster
Slot Christiansen, L.; Munch-Petersen, B.; Knecht, W.
Non-viral deoxyribonucleoside kinases - diversity and practical use
J. Genet. Genomics
42
235-248
2015
Anopheles gambiae (Q86LB8), Bombyx mori (Q9BKL3), Drosophila melanogaster (Q9XZT6)
Jiang, H.; Zhao, L.; Dong, X.; He, A.; Zheng, C.; Johansson, M.; Karlsson, A.; Zheng, X.
Tanshinone IIA enhances bystander cell killing of cancer cells expressing Drosophila melanogaster deoxyribonucleoside kinase in nuclei and mitochondria
Oncol. Rep.
34
1487-1493
2015
Drosophila melanogaster (Q9XZT6), Drosophila melanogaster
Fatima, M.; Ahmed, M.; Batool, F.; Riaz, A.; Ali, M.; Munch-Petersen, B.; Mutahir, Z.
Recombinant deoxyribonucleoside kinase from Drosophila melanogaster can improve gemcitabine based combined gene/chemotherapy for targeting cancer cells
Bosn. J. Basic Med. Sci.
19
342-349
2019
Drosophila melanogaster (Q9XZT6), Drosophila melanogaster
Sun, Y.; Jiang, H.; Gu, M.; Zheng, X.
Efficacy of lentivirus-mediated Drosophila melanogaster deoxyribonucleoside kinase combined with (E)-5-(2-bromovinyl)-2'-deoxyuridine or 1-beta-D-arabinofuranosylthymine therapy in human keloid fibroblasts
Mol. Med. Rep.
18
1660-1665
2018
Drosophila melanogaster (Q9XZT6)
Zhao, Y.; Jiang, H.; Gu, M.; Zu, C.; Zheng, X.
Gemcitabine resistance in triple-negative breast cancer cells can be reverted by Drosophila melanogaster deoxyribonucleoside kinase in the nucleus or cytosol
Oncol. Lett.
20
247
2020
Drosophila melanogaster
Chen, F.; Zhang, Y.; Daugherty, A.B.; Yang, Z.; Shaw, R.; Dong, M.; Lutz, S.; Benner, S.A.
Biological phosphorylation of an unnatural base pair (UBP) using a Drosophila melanogaster deoxynucleoside kinase (DmdNK) mutant
PLoS ONE
12
e0174163
2017
Drosophila melanogaster (Q9XZT6), Drosophila melanogaster
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