Information on EC 2.7.1.74 - deoxycytidine kinase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY
2.7.1.74
-
RECOMMENDED NAME
GeneOntology No.
deoxycytidine kinase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
NTP + deoxycytidine = NDP + dCMP
show the reaction diagram
cytosine arabinoside can act as acceptor, all natural nucleoside triphosphates except dCTP can act as donors
-
-
-
NTP + deoxycytidine = NDP + dCMP
show the reaction diagram
mechanism
-
NTP + deoxycytidine = NDP + dCMP
show the reaction diagram
mechanism; ordered A-B random B-Q reaction sequence
-
NTP + deoxycytidine = NDP + dCMP
show the reaction diagram
random bi-bi mechanism
-
NTP + deoxycytidine = NDP + dCMP
show the reaction diagram
mechanism
-
NTP + deoxycytidine = NDP + dCMP
show the reaction diagram
active site structure, substrate binding structure simulation and analysis
-
NTP + deoxycytidine = NDP + dCMP
show the reaction diagram
substrate-enzyme interactions, bi bi random reaction mechanism with ATP, but ordered with UTP binding before the acceptor substrate, substrate binding site structures
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
purine deoxyribonucleosides salvage
-
pyrimidine deoxyribonucleosides salvage
-
Purine metabolism
-
Pyrimidine metabolism
-
Metabolic pathways
-
SYSTEMATIC NAME
IUBMB Comments
NTP:deoxycytidine 5'-phosphotransferase
Cytosine arabinoside can act as acceptor; all natural nucleoside triphosphates (except dCTP) can act as donors.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
2'-deoxycytidine kinase
-
-
-
-
ara-C kinase
-
-
-
-
arabinofuranosylcytosine kinase
-
-
-
-
dC kinase
-
-
dC kinase
Bacillus megaterium KM
-
-
-
dCK
-
-
-
-
dCK
P43346
-
dCK
Mus musculus C57BL/6J
-
-
-
deoxycytidine kinase
-
-
deoxycytidine-cytidine kinase
-
-
-
-
dNTP:deoxycytidine 5'-phosphotransferase
-
-
kinase, deoxycytidine (phosphorylating)
-
-
-
-
NTP:deoxycytidine 5'-phosphotransferase
P27707
-
CAS REGISTRY NUMBER
COMMENTARY
9039-45-6
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
owl monkey
-
-
Manually annotated by BRENDA team
strain KM
-
-
Manually annotated by BRENDA team
Bacillus megaterium KM
strain KM
-
-
Manually annotated by BRENDA team
; patients with B-cell chronic lymphocytic leukaemia
-
-
Manually annotated by BRENDA team
B-CLL patients
-
-
Manually annotated by BRENDA team
differences in mRNA levels in African and European individuals detected
-
-
Manually annotated by BRENDA team
patients suffering from pancreatic cancer, survival of patients is found to be correlated to the detected enzyme level
-
-
Manually annotated by BRENDA team
patients with pancreatic cancer
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
Ada-/- mice
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
dCK inhibition reduces the induction of apoptosis in thymocytes
malfunction
-
inhibition of the enzyme results in diminished dAdomediated apoptosis in the lungs
malfunction
-
inhibition of the enzyme results in diminished deoxyadenosine-mediated apoptosis in the lungs
malfunction
-
mechanisms of cell killing by activated bromovinyl-deoxyuridine in Jurkat cells expressing thymidine-activating deoxycytidine kinase, cell fate control gene therapy strategy, overview. Tumor formation is repressed by dCK-based cell fate control gene therapy strategy in vivo in a xenogeneic murine model and thymidine-activating dCK mutant increased survival in a stringent model of T cell leukemia
malfunction
-
deoxxycytidine kinase inhibition causes gemcitabine resistance, overview
malfunction
-
dCK inactivation selectively and profoundly affects T and B cell development, severe impact of dCK inactivation on lymphopoiesis. Inactivation of dCK induces a partial block in B cell development
metabolism
-
dCK plays an important role in the salvage pathway of nucleoside metabolism
metabolism
-
deoxycytidine kinase is a rate-limiting enzyme in the deoxyribonucleoside salvage pathway
metabolism
-
2',2'-difluorodeoxycytidine, i.e. gemcitabine, is phosphorylated intracellularly via multiple steps, and the triphosphate inhibits DNA synthesis by interfering with incorporation of endogenous dCTP into DNA, deocycytidine kinase catalyzes the first phosphorylation step, overview
metabolism
-
dCK function in the context of cytosolic deoxycytidine metabolism, model, overview
physiological function
-
cytosolic and mitochondrial deoxynucleoside kinases, as well as 5'-deoxynucleotidases, control intracellular and intramitochondrial phosphorylation of natural nucleotides and nucleoside analogs used in antiviral and cancer chemotherapy, overview
physiological function
-
phosphorylation of Ser74 might be a mechanism for regulating the specificity of the kinase to favor deoxycytidine
physiological function
-
deoxycytidine kinase modulates the impact of the ABC transporter ABCG2 on clofarabine cytotoxicity in Saos-2 cells and OCI-AML3 cells, ABCG2 primarily effluxes clofarabine, but not chlorfarabine-monophosphate, overview
physiological function
-
deoxycitidine kinase is a major enzyme for deoxyadenosine phosphorylation. Hypoxia-induced deoxycytidine kinase expression contributes to apoptosis in chronic lung disease, hypoxia is a regulator of the enzyme
physiological function
-
deoxycitidine kinase is a major enzyme for deoxyadenosine phosphorylation. Hypoxia-induced deoxycytidine kinase expression contributes to apoptosis in chronic lung disease, hypoxia is a regulator of the enzyme. Activating the dAdo-DCK-dATP pathway directly results in increased apoptosis in the lungs of mice with air-space enlargement, the dAdo-DCK pathway is activated in the lungs of Ada-/- mice, overview
physiological function
-
deoxycytidine kinase (dCK) is a rate limiting enzyme critical for phosphorylation of endogenous deoxynucleosides for DNA synthesis and exogenous nucleoside analogues for anticancer and antiviral drug actions. The enzyme is activated in response to DNA damage. Deoxycytidine kinase regulates the G2/M checkpoint through interaction with cyclin-dependent kinase 1 in response to DNA damagereqquiring its phosphorylation at Ser74, overview
physiological function
-
deoxycytidine kinase is a key enzyme in the salvage of deoxyribonucleosides and in the activation of several anticancer and antiviral nucleoside analogues
physiological function
-
deoxycytidine kinase is a rate-limiting enzyme in deoxyribonucleoside salvage, a metabolic pathway that recycles products of DNA degradation. The enzyme phosphorylates and therefore activates nucleoside analogue prodrugs frequently used in cancer, autoimmunity, and viral infections. Normal lymphocyte development critically requires the deoxyribonucleoside salvage pathway
metabolism
Mus musculus C57BL/6J
-
deoxycytidine kinase is a rate-limiting enzyme in the deoxyribonucleoside salvage pathway
-
additional information
-
deoxycytidine kinase is a key enzyme in the activation of several therapeutic nucleoside analogues
additional information
-
structure-function analysis and substrate specificity, overview
additional information
-
structure-function analysis, comparison of wild-type enzyme and mutant S74E
additional information
-
biodistribution of cytosine derivative substrates in mouse healthy and malignant tissues, overview
additional information
Mus musculus C57BL/6J
-
biodistribution of cytosine derivative substrates in mouse healthy and malignant tissues, overview
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2',2'-difluoro-2'-deoxyguanosine + ATP
ADP + 2',2'-difluoro-2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
2'-fluoro-2'-deoxyarabinosylcytidine + ATP
ADP + 2'-fluoro-2'-deoxyarabinosylcytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
2'-fluoro-2'-deoxycytidine + ATP
ADP + 2'-fluoro-2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
2'-O-methyl-cytidine + ATP
ADP + 2'-O-methyl-cytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
2-chloro-2'-deoxyadenosine + NTP
NDP + 2-chloro-2'-deoxy-AMP
show the reaction diagram
-
-
-
-
?
2-chloro-2'-deoxyadenosine + NTP
NDP + 2-chloro-2'-deoxy-AMP
show the reaction diagram
-
-
-
-
?
3'-O-methyl-2'-deoxycytidine + ATP
ADP + 3'-O-methyl-2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
4'-thio-2'-deoxycytidine + UTP
UDP + 4'-thio-2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
4'-thio-beta-D-arabinofuranosylcytosine + UTP
UDP + 4'-thio-beta-D-arabinofuranosylcytosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
9-(beta-D-arabinofuranosyl)-adenine + ATP
9-(beta-D-arabinofuranosyl)-adenine 5'-phosphate + ADP
show the reaction diagram
-
-
-
-
?
9-beta-D-arabinofuranosylguanine + NTP
NDP + 9-beta-D-arabinofuranosylguanine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + (-)-beta-2',3'-dideoxy-3'-thiacytidine
ADP + (-)-beta-2',3'-dideoxy-3'-thiacytidine 5'-phosphate
show the reaction diagram
-
-, i.e. lamivudine
-
-
?
ATP + (E)-5-(2-bromovinyl)-2'-deoxyuridine
ADP + ?
show the reaction diagram
-
substrate of enzyme mutant R104M/D133A, poor substrate of the wild-type enzyme
-
-
?
ATP + 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)cytosine
ADP + 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)cytosine monophosphate
show the reaction diagram
-
-
-
-
?
ATP + 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)cytosine
ADP + 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)cytosine monophosphate
show the reaction diagram
-
-
-
-
?
ATP + 1-(2'-deoxy-2'-fluoro-beta-L-arabinofuranosyl)-5-bromocytosine
ADP + 1-(2'-deoxy-2'-fluoro-beta-L-arabinofuranosyl)-5-bromocytosine monophosphate
show the reaction diagram
-
-
-
-
?
ATP + 1-(2'-deoxy-2'-fluoro-beta-L-arabinofuranosyl)-5-chlorocytosine
ADP + 1-(2'-deoxy-2'-fluoro-beta-L-arabinofuranosyl)-5-chlorocytosine monophosphate
show the reaction diagram
-
-
-
-
?
ATP + 1-(2'-deoxy-2'-fluoro-beta-L-arabinofuranosyl)-5-methylcytosine
ADP + 1-(2'-deoxy-2'-fluoro-beta-L-arabinofuranosyl)-5-methylcytosine monophosphate
show the reaction diagram
-
-
-
-
?
ATP + 1-(2-deoxy-beta-D-ribofuranosyl)-isocarbostyril
ADP + ?
show the reaction diagram
-
poor substrate, 1.4% of the activity with 2'-deoxycytidine
-
-
?
ATP + 1-beta-D-arabinofuranosylcytosine
ADP + 1-beta-D-arabinofuranosylcytosine 5'-phosphate
show the reaction diagram
-
-
-
-
-
ATP + 1-beta-D-arabinosylcytosine
ADP + 1-beta-D-arabinosylcytosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 2',2'-difluoro-2'-deoxycytidine
ADP + 2',2'-difluoro-2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
i.e. gemcitabine
-
-
?
ATP + 2',2'-difluorodeoxycytidine
ADP + 2',2'-difluorodeoxycytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 2',2'-difluorodeoxycytidine
ADP + 2',2'-difluorodeoxycytidine 5'-phosphate
show the reaction diagram
-
i.e. gemcitabine
-
-
?
ATP + 2',2'-difluorodeoxycytidine
ADP + 2',2'-difluorodeoxycytidine 5'-monophosphate
show the reaction diagram
-
i.e. gemcitabine
-
-
?
ATP + 2',2'-difluorodeoxycytidine
ADP + 2',2'-difluorodeoxycytidine monophosphate
show the reaction diagram
-
i.e. gemcitabine, i.e. gemcitabine, transport and metabolism in vivo, overview
-
-
?
ATP + 2',3'-dideoxycytidine
ADP + 2',3'-dideoxycytidine 5'-phosphate
show the reaction diagram
P27707
i.e. zalcitabine
-
-
?
ATP + 2'-deoxy-3'-thiacytidine
ADP + 2'-deoxy-3'-thiacytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
P27707
-
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
P43346
-
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides, supplying cells with deoxyribonucleotides for DNA replicative and repair synthesis
-
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
P27707
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
P43346
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
involved in nucleotide synthesis, involved in DNA repair
-
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides
-
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides, supplying cells with deoxyribonucleotides for DNA replicative and repair synthesis
-
-
?
ATP + 2'-deoxycytidine
ADP + 5'-dCMP
show the reaction diagram
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 5'-dCMP
show the reaction diagram
-
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 5'-dCMP
show the reaction diagram
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 5'-dCMP
show the reaction diagram
-
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 5'-dCMP
show the reaction diagram
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 5'-dCMP
show the reaction diagram
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 5'-dCMP
show the reaction diagram
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 5'-dCMP
show the reaction diagram
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 5'-dCMP
show the reaction diagram
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 5'-dCMP
show the reaction diagram
-
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 5'-dCMP
show the reaction diagram
-
best phosphate donor cytosolic isozyme II and mitochondrial isozyme
-
?
ATP + 2'-deoxycytidine
ADP + 5'-dCMP
show the reaction diagram
-
best phosphate donor
-
?
ATP + 2'-deoxycytidine
ADP + 5'-dCMP
show the reaction diagram
-
in the presence of DTT less effective than dUTP, UTP, dTTP or GTP, without DTT only less effective than dUTP
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxy-CMP
show the reaction diagram
-
-
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
P27707
-
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
P43346
-
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides
-
-
?
ATP + 2,5-difluoro-4-[1-(2-deoxy-beta-L-ribofuranosyl)]-aniline
ADP + ?
show the reaction diagram
-
nucleoside mimic, 14.6% of the activity with 2'-deoxycytidine
-
-
?
ATP + 2-chloro-2'-deoxyadenosine
ADP + 2-chloro-2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
i.e. cladribine
-
-
?
ATP + 2-chloro-2'-deoxyadenosine
ADP + 2-chloro-2'-deoxyadenosine 5'-phosphate
show the reaction diagram
P27707
i.e. cladribine
-
-
?
ATP + 2-chlorodeoxyadenosine
ADP + 2-chlorodeoxyadenosine 5'-phosphate
show the reaction diagram
-
i.e. cladribine
-
-
?
ATP + 5-(3-pyridyl)-2'-deoxycytidine
ADP + 5-(3-pyridyl)-2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
cytosolic enzyme, poor substrate
-
-
?
ATP + 5-(4-pyridyl)-2'-deoxycytidine
ADP + 5-(4-pyridyl)-2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
cytosolic enzyme, poor substrate
-
-
?
ATP + 5-bromodeoxycytidine
ADP + 5-bromo-dCMP
show the reaction diagram
-
-
-
-
?
ATP + 5-iododeoxycytidine
ADP + 5-iodo-dCMP
show the reaction diagram
-
-
-
-
?
ATP + 5-methyldeoxycytidine
ADP + 5-methyl-dCMP
show the reaction diagram
-
-
-
-
?
ATP + 5-propynyldeoxycytidine
ADP + 5-propynyl-dCMP
show the reaction diagram
-
-
-
-
?
ATP + adenosine
ADP + adenosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + arabinosyl adenine
ADP + arabinosyl adenine 5'-phosphate
show the reaction diagram
P27707
-
-
-
?
ATP + arabinosyl cytosine
ADP + arabinosyl cytosine 5'-phosphate
show the reaction diagram
-
i.e. cytosar
-
-
?
ATP + arabinosyl cytosine
ADP + arabinosyl cytosine 5'-phosphate
show the reaction diagram
P27707
i.e. cytosar
-
-
?
ATP + beta-L-2',3'-dideoxy-3'-thiacytidine
ADP + beta-L-2',3'-dideoxy-3'-thiacytidine 5'-phosphate
show the reaction diagram
P27707
-
-
-
?
ATP + cladribine
ADP + cladribine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + cladribine
ADP + phospho-cladribine
show the reaction diagram
-
-
-
-
?
ATP + clofarabine
ADP + phospho-clofarabine
show the reaction diagram
-
-
-
-
?
ATP + clofarabine
ADP + phospho-clofarabine
show the reaction diagram
-
-
-
-
?
ATP + clofarabine
ADP + phospho-clofarabine
show the reaction diagram
Mus musculus C57BL/6J
-
-
-
-
?
ATP + cytarabine
ADP + cytarabine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + cytarabine
ADP + cytarabine 5'-phosphate
show the reaction diagram
-
drug against acute myeloid and lymphoblastic leukemia, i.e. 1-beta-D-arabinofuranosylcytosine
-
-
?
ATP + cytidine
ADP + ?
show the reaction diagram
-
-
-
-
?
ATP + cytidine
ADP + ?
show the reaction diagram
-
-
-
-
?
ATP + cytidine
ADP + ?
show the reaction diagram
-
not
-
-
-
ATP + cytidine
ADP + ?
show the reaction diagram
-
poor: beta-isomer, not: alpha-isomer
-
-
?
ATP + cytidine
ADP + cytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-2'-deoxycytidine
ADP + D-2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-deoxycytidine
ADP + D-dCMP
show the reaction diagram
-
-
-
-
?
ATP + D-deoxythymidine
ADP + D-dTMP
show the reaction diagram
-
-
-
-
?
ATP + D-deoxyuridine
ADP + D-dUMP
show the reaction diagram
-
-
-
-
?
ATP + deoxyadenosine
ADP + dAMP
show the reaction diagram
-
-
-
-
?
ATP + deoxyadenosine
ADP + dAMP
show the reaction diagram
-
-
-
-
?
ATP + deoxyadenosine
ADP + dAMP
show the reaction diagram
Mus musculus C57BL/6J
-
-
-
-
?
ATP + deoxycytidine
ADP + dCMP
show the reaction diagram
-
-
-
-
?
ATP + deoxycytidine
ADP + dCMP
show the reaction diagram
-
-
-
-
?
ATP + deoxycytidine
ADP + dCMP
show the reaction diagram
-
-
-
-
?
ATP + deoxycytidine
ADP + dCMP
show the reaction diagram
-
-
-
-
?
ATP + deoxycytidine
ADP + dCMP
show the reaction diagram
-
-
-
-
?
ATP + deoxycytidine
ADP + dCMP
show the reaction diagram
Mus musculus C57BL/6J
-
-
-
-
?
ATP + deoxycytidine
ADP + dCMP
show the reaction diagram
Bacillus megaterium KM
-
-
-
-
?
ATP + deoxycytidine
ADP + ?
show the reaction diagram
-
-
-
-
?
ATP + deoxycytidine
ADP + ?
show the reaction diagram
-
key enzyme in anabolic phosphorylation of deoxyribonucleosides and their analogues
-
-
?
ATP + deoxycytidine
ADP + ?
show the reaction diagram
-
key anabolic enzyme for activation of purine or pyrimidine deoxynucleosides as well as cytidine arabinoside and other anti-tumor drugs
-
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
-
-
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
-
-
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
Mus musculus C57BL/6J
-
-
-
-
?
ATP + dideoxythymidine
ADP + dideoxythymidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + difluoro-arabinofuranosyl adenine
ADP + difluoro-arabinofuranosyl adenine 5'-phosphate
show the reaction diagram
P27707
i.e. fludarabine
-
-
?
ATP + difluorodeoxycytidine
ADP + difluorodeoxycytidine 5'-phosphate
show the reaction diagram
P27707
i.e. gemcitabine
-
-
?
ATP + fludarabine
ADP + fludarabine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + fludarabine
ADP + phospho-fludarabine
show the reaction diagram
-
-
-
-
?
ATP + gemcitabine
ADP + gemcitabine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + gemcitabine
ADP + gemcitabine 5'-phosphate
show the reaction diagram
-
i.e. difluorodeoxycytidine
-
-
?
ATP + gemcitabine
ADP + phospho-gemcitabine
show the reaction diagram
-
-
-
-
?
ATP + L-2',3'-dideoxy-3'-thiacytidine
ADP + L-2',3'-dideoxy-3'-thiacytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + L-2'-deoxycytidine
ADP + L-2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + L-deoxythymidine
ADP + L-dTMP
show the reaction diagram
-
-
-
-
?
ATP + L-deoxyuridine
ADP + L-dUMP
show the reaction diagram
-
-
-
-
?
ATP + L-thymidine
?
show the reaction diagram
-
human dCK, in addition to being able to phosphorylate both purines and pyrimidines, has the special ability to accept L-nucleosides as substrates
-
-
?
ATP + lamivudine
ADP + lamivudine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + thymidine
ADP + TMP
show the reaction diagram
-
-
-
-
?
ATP + thymidine
ADP + TMP
show the reaction diagram
-
cytosolic enzyme, poor substrate
-
-
?
ATP + troxacitabine
ADP + troxacitabine 5'-phosphate
show the reaction diagram
-
-
-
-
?
beta-D-3'-hydroxymethyl-2',3'dideoxycytidine + ATP
ADP + beta-D-3'-hydroxymethyl-2',3'dideoxycytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
CTP + 2'-deoxycytidine
CDP + 2'-deoxy-CMP
show the reaction diagram
-
-
-
-
-
CTP + 2'-deoxycytidine
CDP + 2'-deoxy-CMP
show the reaction diagram
-
-
-
-
?
CTP + 2'-deoxycytidine
CDP + 2'-deoxy-CMP
show the reaction diagram
-
-
-
-
?
CTP + 2'-deoxycytidine
CDP + 2'-deoxy-CMP
show the reaction diagram
-
poor
-
-
?
CTP + 2'-deoxycytidine
CDP + 2'-deoxy-CMP
show the reaction diagram
-
as good as GTP, UTP, dATP, mitochondrial isozyme
-
-
?
CTP + deoxycytidine
CDP + dCMP
show the reaction diagram
Bacillus megaterium, Bacillus megaterium KM
-
-
-
-
?
dATP + deoxycytidine
dADP + dCMP
show the reaction diagram
Bacillus megaterium, Bacillus megaterium KM
-
-
-
-
?
dCTP + 2'-deoxycytidine
dCDP + 2'-deoxy-CMP
show the reaction diagram
-
only in the absence of ATP
-
-
?
dCTP + deoxycytidine
dCDP + dCMP
show the reaction diagram
Bacillus megaterium, Bacillus megaterium KM
-
-
-
-
?
dGTP + 2'-deoxycytidine
dGDP + 2'-deoxy-CMP
show the reaction diagram
-
-
-
-
?
dGTP + 2'-deoxycytidine
dGDP + 2'-deoxy-CMP
show the reaction diagram
-
-
-
-
?
dGTP + 2'-deoxycytidine
dGDP + 2'-deoxy-CMP
show the reaction diagram
-
cytosolic isozyme I
-
-
?
dGTP + 2'-deoxycytidine
dGDP + 2'-deoxy-CMP
show the reaction diagram
-
best phosphate donor
-
-
?
dGTP + 2'-deoxycytidine
dGDP + 2'-deoxy-CMP
show the reaction diagram
-
best phosphate donor
-
-
?
dGTP + 2'-deoxycytidine
dGDP + 2'-deoxy-CMP
show the reaction diagram
-
poor substrate of mitochondrial isozyme
-
-
?
dGTP + deoxycytidine
dGDP + dCMP
show the reaction diagram
Bacillus megaterium, Bacillus megaterium KM
-
-
-
-
?
dTTP + 2'-deoxycytidine
dTDP + 2'-deoxy-CMP
show the reaction diagram
-
-
-
-
-
dTTP + 2'-deoxycytidine
dTDP + 2'-deoxy-CMP
show the reaction diagram
-
-
-
-
?
dTTP + 2'-deoxycytidine
dTDP + 2'-deoxy-CMP
show the reaction diagram
-
-
-
-
?
dTTP + deoxycytidine
dTDP + dCMP
show the reaction diagram
-
-
-
-
?
dUTP + 2'-deoxycytidine
dUDP + 2'-deoxy-CMP
show the reaction diagram
-
best phosphate donor
-
-
?
dUTP + 2'-deoxycytidine
dUDP + 2'-deoxy-CMP
show the reaction diagram
-
best phosphate donor, cytosolic enzyme I, poor, mitochondrial isozyme
-
-
?
GTP + 2'-deoxycytidine
GDP + 2'-deoxy-CMP
show the reaction diagram
-
-
-
-
-
GTP + 2'-deoxycytidine
GDP + 2'-deoxy-CMP
show the reaction diagram
-
-
-
-
?
GTP + 2'-deoxycytidine
GDP + 2'-deoxy-CMP
show the reaction diagram
-
-
-
-
?
GTP + 2'-deoxycytidine
GDP + 2'-deoxy-CMP
show the reaction diagram
-
as good as ATP
-
-
?
GTP + 2'-deoxycytidine
GDP + 2'-deoxy-CMP
show the reaction diagram
-
best phosphate donor
-
-
?
GTP + 2'-deoxycytidine
GDP + 2'-deoxy-CMP
show the reaction diagram
-
as good as dGTP, dTTP or dUTP, cytosolic isozyme I, as good as CTP, dATP or UTP, mitochondrial isozyme
-
-
?
NTP + (-)-beta-2',3'-dideoxy-3'-thiacytidine
NDP + (-)-beta-2',3'-dideoxy-3'-thiacytidine 5'-phosphate
show the reaction diagram
-
activation of the clinically relevant substrate
-
-
?
NTP + 1-beta-D-arabinofuranosylcytosine
NDP + 1-beta-D-arabinofuranosylcytosine 5'-phosphate
show the reaction diagram
-
antineoplastic agent
-
-
?
NTP + 1-beta-D-arabinofuranosylcytosine
NDP + 1-beta-D-arabinofuranosylcytosine 5'-phosphate
show the reaction diagram
-
i.e. cytarabine, rate limiting enzyme in the activation of the prodrug
-
-
?
NTP + 1-beta-D-arabinosylcytosine
NDP + 1-beta-D-arabinosylcytosine 5'-phosphate
show the reaction diagram
-
i.e. cytaribine, activation of the pharmaceutically relevant substrate which is commonly used in the treatment of lymphoproliferative malignancies
-
-
?
NTP + 2',2'-difluoro-2'-deoxycytidine
NDP + 2',2'-difluoro-2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
best acceptor substrate, best phosphate donors: UTP or NTP-mixture, better than ATP
-
-
?
NTP + 2',2'-difluoro-2'-deoxycytidine
NDP + 2',2'-difluoro-2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
cytosolic isozyme I, not mitochondrial isozyme
-
-
?
NTP + 2',2'-difluorodeoxycytidine
NDP + 2',2'-difluorodeoxycytidine 5'-phosphate
show the reaction diagram
-
i.e. gemcitabine, activation of the pharmaceutically relevant substrate which is commonly used in the treatment of solid malignant tumors
-
-
?
NTP + 2',2'-difluorodeoxycytidine
NDP + 2',2'-difluorodeoxycytidine 5'-phosphate
show the reaction diagram
-
i.e. gemcitabine, rate limiting enzyme in the activation of the pharmaceutically relevant substrate which is commonly used in the treatment of solid malignant tumors
-
-
?
NTP + 2',2'-difluorodeoxycytidine
NDP + 2',2'-difluorodeoxycytidine 5'-phosphate
show the reaction diagram
-
i.e. gemcitabine, rate limiting enzyme in the activation of the pharmaceutically relevant substrate which is commonly used in the treatment of tumors
-
-
?
NTP + 2',2'-difluorodeoxycytidine
NDP + 2',2'-difluorodeoxycytidine 5'-phosphate
show the reaction diagram
-
substrate also termed gemcitabine
-
-
?
NTP + 2',3'-dideoxycytidine
NDP + 2',3'-dideoxycytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
NTP + 2',3'-dideoxycytidine
NDP + 2',3'-dideoxycytidine 5'-phosphate
show the reaction diagram
-
poor
-
-
?
NTP + 2',3'-dideoxycytidine
NDP + 2',3'-dideoxycytidine 5'-phosphate
show the reaction diagram
-
antiviral agent
-
-
?
NTP + 2',3'-dideoxycytidine
NDP + 2',3'-dideoxycytidine 5'-phosphate
show the reaction diagram
-
i.e. zalcitabine, activation of the pharmaceutically relevant substrate which is used in the treatment of HIV infections
-
-
?
NTP + 2'-deoxy-3'-thiacytidine
NDP + 2'-deoxy-3'-thiacytidine 5'-phosphate
show the reaction diagram
-
antiviral agent
-
-
?
NTP + 2'-deoxy-3'-thiacytidine
NDP + 2'-deoxy-3'-thiacytidine 5'-phosphate
show the reaction diagram
-
i.e. lamivudine, activation of the pharmaceutically relevant substrate which is used in the treatment of HIV infections
-
-
?
NTP + 2'-deoxyadenosine
NDP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
NTP + 2'-deoxyadenosine
NDP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides
-
-
?
NTP + 2'-deoxycytidine
NDP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
NTP + 2'-deoxycytidine
NDP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
more effective substrate than 2'-deoxyadenosine and 2'-deoxyguanosine
-
-
?
NTP + 2'-deoxycytidine
NDP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides
-
-
?
NTP + 2'-deoxyguanosine
NDP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
NTP + 2'-deoxyguanosine
NDP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides
-
-
?
NTP + 2-chloro-2'-deoxyadenosine
NDP + 2-chloro-2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
NTP + 2-chloro-2'-deoxyadenosine
NDP + 2-chloro-2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
i.e. cladribine, activation of the pharmaceutically relevant substrate which is commonly used in the treatment of lymphoproliferative malignancies
-
-
?
NTP + 2-chloro-2'-deoxyadenosine
NDP + 2-chloro-2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
i.e. cladribine, antineoplastic agent
-
-
?
NTP + 2-chloro-2'-deoxyadenosine
NDP + 2-chloro-2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
phosphorylation of chemotherapeutically important nucleoside analogues
-
-
?
NTP + 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-9H-purin-6-amine
NDP + 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-9H-purin-6-amine 5'-phosphate
show the reaction diagram
-
i.e. clofarabine, rate-limiting step in the activation of the prodrug, precursor of an effective chemotherapeutic agent for leukemias and other haematological malignancies
-
-
?
NTP + 9-beta-D-arabinofuranosyl-2-fluoroadenine
NDP + 9-beta-D-arabinofuranosyl-2-fluoroadenine 5'-phosphate
show the reaction diagram
-
-
-
-
?
NTP + 9-beta-D-arabinosyl 2-fluoroadenine
NDP + 9-beta-D-arabinosyl 2-fluoroadenine 5'-phosphate
show the reaction diagram
-
activation of the pharmaceutically relevant substrate which is commonly used in the treatment of lymphoproliferative malignancies
-
-
?
NTP + 9-beta-D-arabinosyl 2-fluoroadenine
NDP + 9-beta-D-arabinosyl 2-fluoroadenine 5'-phosphate
show the reaction diagram
-
i.e. fludarabine, activation of the pharmaceutically relevant substrate which is commonly used in the treatment of lymphoproliferative malignancies
-
-
?
NTP + 9-beta-D-arabinosyl-2-fluoroadenine
NDP + 9-beta-D-arabinosyl-2-fluoroadenine 5'-phosphate
show the reaction diagram
-
phosphorylation of chemotherapeutically important nucleoside analogues
-
-
?
NTP + beta-D-2'-deoxythioguanosine
NDP + ?
show the reaction diagram
-
not alpha-isomer
-
-
?
NTP + cytosine arabinoside
NDP + cytosine arabinoside 5'-monophosphate
show the reaction diagram
-
-
-
-
?
NTP + cytosine arabinoside
NDP + cytosine arabinoside 5'-monophosphate
show the reaction diagram
-
-
-
-
?
NTP + cytosine arabinoside
NDP + cytosine arabinoside 5'-monophosphate
show the reaction diagram
-
-
-
-
?
NTP + cytosine arabinoside
NDP + cytosine arabinoside 5'-monophosphate
show the reaction diagram
-
ATP can be replaced by GTP, dATP, dGTP or dTTP
-
?
NTP + cytosine arabinoside
NDP + cytosine arabinoside 5'-monophosphate
show the reaction diagram
-
D-isomer
-
-
?
NTP + cytosine arabinoside
NDP + cytosine arabinoside 5'-monophosphate
show the reaction diagram
-
best phosphate donors: UTP or NTP-mixture, even better than ATP
-
-
?
NTP + cytosine arabinoside
NDP + cytosine arabinoside 5'-monophosphate
show the reaction diagram
-
cytosolic isozyme I, no acceptor substrate for cytosolic isozyme II or mitochondrial isozyme
-
-
?
NTP + cytosine arabinoside
NDP + cytosine arabinoside 5'-monophosphate
show the reaction diagram
-
i.e. 1-beta-arabinofuranosyl cytosine, L-isomer better substrate than D-isomer
-
-
?
NTP + deoxyadenosine
NDP + dAMP
show the reaction diagram
-
-
-
-
?
NTP + deoxyadenosine
NDP + dAMP
show the reaction diagram
-
-
-
-
?
NTP + deoxyadenosine
NDP + dAMP
show the reaction diagram
-
-
-
-
?
NTP + deoxyadenosine
NDP + dAMP
show the reaction diagram
-
-
-
-
?
NTP + deoxyadenosine
NDP + dAMP
show the reaction diagram
-
-
-
-
?
NTP + deoxyadenosine
NDP + dAMP
show the reaction diagram
-
not
-
-
-
NTP + deoxyadenosine
NDP + dAMP
show the reaction diagram
-
poor
-
-
?
NTP + deoxyadenosine
NDP + dAMP
show the reaction diagram
-
cytosolic isozyme I, not mitochondrial isozyme
-
-
?
NTP + deoxyadenosine
NDP + dAMP
show the reaction diagram
Lactobacillus acidophilus R-26
-
-
-
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
-
-
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
-
-
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
-
-
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
-
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
-
-
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
-
-
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
-
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
-
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
-
-
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
-
-
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
-
-
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
specificity
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
no substrate: phosphate
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
no substrate: dCTP
-
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
no substrate: dCTP
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
no substrate: guanosine
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
no substrate: guanosine
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
poor substrate: arabinosyl-CTP
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
enzyme shows little specificity towards phosphate donor
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
enzyme shows little specificity towards phosphate donor
-
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
enzyme shows little specificity towards phosphate donor
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
in order of decreasing activity: dGTP, CTP, ATP, dATP, dTTP, UTP, GTP
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
no substrate: beta-gamma-methylene diphosphonate analogue of dTTP
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
no substrate: ribavirin
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
no substrate: uridine arabinoside, cytosine
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
beta-D-2'-deoxyribonucleosides are more efficient than corresponding beta-D-arabinonucleosides or beta-ribonucleosides, rather nonspecific for base moiety of nucleoside substrate
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
no substrate: adenosine, uridine
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
no substrate: adenosine, uridine
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
no substrate: adenosine, uridine
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
no substrate: nucleoside diphosphates and their deoxy derivatives
-
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
poor substrate: beta-5-azacytidine
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
no substrate: deoxyuridine
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
best acceptor substrate at low substrate concentrations
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
no substrate: thymidine
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
Lactobacillus acidophilus R-26
-
-
-
-
?
NTP + deoxyguanosine
NDP + dGMP
show the reaction diagram
-
-
-
-
?
NTP + deoxyguanosine
NDP + dGMP
show the reaction diagram
-
-
-
-
?
NTP + deoxyguanosine
NDP + dGMP
show the reaction diagram
-
not
-
-
-
NTP + deoxyguanosine
NDP + dGMP
show the reaction diagram
-
cytosolic isozyme I, not mitochondrial isozyme
-
-
?
NTP + deoxythymidine
NDP + dTMP
show the reaction diagram
-
mitochondrial isozyme, better than deoxycytidine, not cytosolic isozyme I
-
-
?
NTP + deoxyuridine
NDP + dUMP
show the reaction diagram
-
mitochondrial isozyme, not cytosolic isozyme I
-
-
?
NTP + deoxyuridine
NDP + dUMP
show the reaction diagram
-
cytosolic enzyme, poor substrate
-
-
?
NTP + troxacitabine
?
show the reaction diagram
-
activation of the clinically relevant substrate
-
-
?
UTP + (-)-beta-2',3'-dideoxy-3'-thiacytidine
UDP + (-)-beta-2',3'-dideoxy-3'-thiacytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
UTP + 1-beta-D-arabinofuranosylcytosine
UDP + 1-beta-D-arabinofuranosylcytosine 5'-phosphate
show the reaction diagram
-
i.e. cytarabine
-
-
?
UTP + 2',2'-difluorodeoxycytidine
UDP + 2',2'-difluorodeoxycytidine 5'-phosphate
show the reaction diagram
-
i.e. gemcitabine
-
-
?
UTP + 2',3'-dideoxycytidine
UDP + 2',3'-dideoxycytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
UTP + 2',3'-dideoxycytidine
UDP + 2',3'-dideoxycytidine 5'-phosphate
show the reaction diagram
P27707
i.e. zalcitabine
-
-
?
UTP + 2',3'-dideoxycytidine
UDP + 2',3'-dideoxycytidine 5'-phosphate
show the reaction diagram
-
i.e. zalcitabine, activation of the pharmaceutically relevant substrate which is used for the treatment of HIV infections
-
-
?
UTP + 2'-deoxy-3'-thiacytidine
UDP + 2'-deoxy-3'-thiacytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
UTP + 2'-deoxy-3'-thiacytidine
UDP + 2'-deoxy-3'-thiacytidine 5'-phosphate
show the reaction diagram
-
i.e. lamivudine, activation of the pharmaceutically relevant substrate which is used for the treatment of HIV infections
-
-
?
UTP + 2'-deoxyadenosine
UDP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
UTP + 2'-deoxyadenosine
UDP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
P27707
-
-
-
?
UTP + 2'-deoxyadenosine
UDP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
UTP + 2'-deoxyadenosine
UDP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides
-
-
?
UTP + 2'-deoxyadenosine
UDP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides, supplying cells with deoxyribonucleotides for DNA replicative and repair synthesis
-
-
?
UTP + 2'-deoxycytidine
UDP + 2'-deoxy-CMP
show the reaction diagram
-
-
-
-
?
UTP + 2'-deoxycytidine
UDP + 2'-deoxy-CMP
show the reaction diagram
-
-
-
-
?
UTP + 2'-deoxycytidine
UDP + 2'-deoxy-CMP
show the reaction diagram
-
poor
-
-
?
UTP + 2'-deoxycytidine
UDP + 2'-deoxy-CMP
show the reaction diagram
-
best phosphate donor at low substrate levels, as good as CTP, GTP or dATP
-
-
?
UTP + 2'-deoxycytidine
UDP + 2'-deoxy-CMP
show the reaction diagram
-
as good as CTP, GTP or dATP
-
-
?
UTP + 2'-deoxycytidine
UDP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
P27707
-
-
-
?
UTP + 2'-deoxycytidine
UDP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
UTP + 2'-deoxycytidine
UDP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
preferred donor and acceptor substrates
-
-
?
UTP + 2'-deoxycytidine
UDP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides
-
-
?
UTP + 2'-deoxycytidine
UDP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides, supplying cells with deoxyribonucleotides for DNA replicative and repair synthesis
-
-
?
UTP + 2'-deoxyguanosine
UDP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
UTP + 2'-deoxyguanosine
UDP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
P27707
-
-
-
?
UTP + 2'-deoxyguanosine
UDP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
UTP + 2'-deoxyguanosine
UDP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides
-
-
?
UTP + 2-chloro-2'-deoxyadenosine
UDP + 2-chloro-2'-deoxyadenosine 5'-phosphate
show the reaction diagram
P27707
i.e. cladribine
-
-
?
UTP + 2-chloro-2'-deoxyadenosine
UDP + 2-chloro-2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
i.e. cladribine
-
-
?
UTP + 2-chlorodeoxyadenosine
UDP + 2-chlorodeoxyadenosine 5'-phosphate
show the reaction diagram
-
i.e. cladribine
-
-
?
UTP + 2-fluoro-9-beta-D-arabinofuranosyladenine
UDP + 2-fluoro-9-beta-D-arabinofuranosyladenine 5'-phosphate
show the reaction diagram
-
i.e. fludarabine
-
-
?
UTP + 9-beta-D-arabinofuranosylguanine
UDP + 9-beta-D-arabinofuranosylguanine 5'-phosphate
show the reaction diagram
-
i.e. nelarabine
-
-
?
UTP + adenosine
UDP + adenosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
UTP + arabinosyl adenine
UDP + arabinosyl adenine 5'-phosphate
show the reaction diagram
P27707
-
-
-
?
UTP + arabinosyl cytosine
UDP + arabinosyl cytosine 5'-phosphate
show the reaction diagram
-
i.e. cytosar
-
-
?
UTP + arabinosyl cytosine
UDP + arabinosyl cytosine 5'-phosphate
show the reaction diagram
P27707
i.e. cytosar
-
-
?
UTP + beta-L-2',3'-dideoxy-3'-thiacytidine
UDP + beta-L-2',3'-dideoxy-3'-thiacytidine 5'-phosphate
show the reaction diagram
P27707
-
-
-
?
UTP + beta-L-dioxolane-cytidine
UDP + beta-L-dioxolane-cytidine 5'-phosphate
show the reaction diagram
P27707
antitumor drug
-
-
?
UTP + cladribine
UDP + cladribine 5'-phosphate
show the reaction diagram
-
-
-
-
?
UTP + cladribine
UDP + phospho-cladribine
show the reaction diagram
-
-
-
-
?
UTP + clofarabine
UDP + phospho-clofarabine
show the reaction diagram
-
-
-
-
?
UTP + cytidine
UDP + cytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
UTP + D-2'-deoxycytidine
UDP + D-2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
UTP + deoxyadenosine
UDP + dAMP
show the reaction diagram
-
-
-
-
?
UTP + deoxycytidine
UDP + dCMP
show the reaction diagram
-
-
-
-
?
UTP + deoxycytidine
UDP + dCMP
show the reaction diagram
-
UTP is physiological phosphate donor
-
-
?
UTP + deoxyguanosine
UDP + dGMP
show the reaction diagram
-
-
-
-
?
UTP + difluoro-arabinofuranosyl adenine
UDP + difluoro-arabinofuranosyl adenine 5'-phosphate
show the reaction diagram
P27707
i.e. fludarabine
-
-
?
UTP + difluorodeoxycytidine
UDP + difluorodeoxycytidine 5'-phosphate
show the reaction diagram
P27707
i.e. gemcitabine
-
-
?
UTP + fludarabine
UDP + fludarabine 5'-phosphate
show the reaction diagram
-
-
-
-
?
UTP + fludarabine
UDP + phospho-fludarabine
show the reaction diagram
-
-
-
-
?
UTP + gemcitabine
UDP + gemcitabine 5'-phosphate
show the reaction diagram
-
-
-
-
?
UTP + L-2',3'-dideoxy-3'-thiacytidine
UDP + L-2',3'-dideoxy-3'-thiacytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
UTP + L-2'-deoxycytidine
UDP + L-2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
UTP + troxacitabine
UDP + troxacitabine 5'-phosphate
show the reaction diagram
-
-
-
-
?
GTP + deoxycytidine
GDP + dCMP
show the reaction diagram
-
optimal activity with GTP as phosphoryl donor
-
-
?
additional information
?
-
-
purine deoxynucleoside activity inseparably associated with deoxycytidine kinase protein
-
-
-
additional information
?
-
-
multisubstrate enzyme, that also phosphorylates purine deoxyribonucleotides
-
-
-
additional information
?
-
-
remarkably relaxed enantioselectivity with respect to cytidine derivatives in beta configuration
-
-
-
additional information
?
-
-
enzyme has two separate active sites for deoxycytidine and deoxyadenosine activity
-
-
-
additional information
?
-
-
several isozymes: cytosolic deoxycytidine kinase I and II, plus mitochondrial isozyme
-
-
-
additional information
?
-
-
lack of enantioselectivity for D- and L-analogues of cytidine and adenosine
-
-
-
additional information
?
-
-
presumably one common nucleoside acceptor site
-
-
-
additional information
?
-
-
enzyme exists in different conformational states with different substrate kinetic properties
-
-
-
additional information
?
-
-
reacts with both enantiomers of beta-deoxycytidine, beta-deoxyguanidine, beta-deoxyadenosine, and alpha-D-deoxycytidine is also substrate
-
-
-
additional information
?
-
-
reacts with both enantiomers of beta-deoxyadenosine, beta-arabinofuranosyl-adenine and beta-deoxyguanine
-
-
-
additional information
?
-
-
5'-phosphorylation of is a crucial step in metabolic activation of anticancer and antiviral nucleoside antimetabolites, such as cladribine, gemcitabine, cytarabine, and lamivudine
-
-
-
additional information
?
-
-
de novo synthesis and salvage of ribonucleotides and deoxyribonucleotides, metabolism overview, enzyme is active and medically important in anticancer and antiviral therapy due to high phosphorylation activity of prodrugs, overview
-
-
-
additional information
?
-
-
enzyme is active and medically important in anticancer and antiviral therapy due to high phosphorylation activity of prodrugs, overview
-
-
-
additional information
?
-
-
resistance of cells to cytarabine is caused by dCK enzyme deficiency
-
-
-
additional information
?
-
-
the activation of the enzyme is a first step in 2-chloro-2'-deoxyadenosine-induced cytotoxicity
-
-
-
additional information
?
-
-
the earliest nucleotide kinase in evolution, probably encoded by the so-called dCK/dGK/TK2-like gene, is the progenitor gene, several duplications of it are the reason for evolutionary occurrence of nucleoside kinases with strict substrate specificities in other organism, phylogenetic tree, overview
-
-
-
additional information
?
-
P43346
the earliest nucleotide kinase in evolution, probably encoded by the so-called dCK/dGK/TK2-like gene, is the progenitor gene, several duplications of it are the reason for evolutionary occurrence of nucleoside kinases with strict substrate specificities in other organism, phylogenetic tree, overview
-
-
-
additional information
?
-
-
the enzyme is active and important in activation of several clinically important deoxynucleoside analogues used for the treatment of haematological and solid malignancies
-
-
-
additional information
?
-
-
broad substrate specificity, overview, binding of acceptor subtrates is more tightly in presence of phosphate donor molecules
-
-
-
additional information
?
-
-
dioxolane guanosine is no substrate
-
-
-
additional information
?
-
-
enzyme can utilizes several phosphate donors, with preference for UTP
-
-
-
additional information
?
-
-
no activity with several difluorophenyl nucleoside analogues and with 1-(2-deoxy-beta-D-ribofuranosyl)-7-iodoisocarbostyril, overview
-
-
-
additional information
?
-
P27707
substrate-enzyme interactions, overview, enzyme prefers nucleosides with sugars in the S-conformation, i.e C2'-endo-C3'-exo, binding of substrate induces conformational changes, the phosphate donor influences the acceptor substrate specificity, mechanism, overview
-
-
-
additional information
?
-
-
the enzyme shows broad substrate specificity
-
-
-
additional information
?
-
-
catalyzes the rate-limiting step of the deoxyribonucleoside salvage pathway, key role in the activation of numerous nucleoside analogues used in anti-cancer and antiviral chemotherapy
-
-
-
additional information
?
-
-
dCK is able to phosphorylate both D- and L-nucleosides and nucleoside analogs
-
-
-
additional information
?
-
-
enzyme of the salvage pathway for deoxyribonucleotide synthesis, which provides resting cells with deoxynucleotides for DNA repair and mitochondrial DNA synthesis, important enzyme for the phosphorylation/activation of deoxynucleoside analogues, which are cytotoxic towards both replicating and indolent malignancies
-
-
-
additional information
?
-
-
essential for the synthesis of deoxynucleotides required for DNA repair and involved in deoxynucleoside analogue activation
-
-
-
additional information
?
-
-
key enzyme in the deoxynucleoside salvage pathway and in the activation of numerous nucleoside analogues used in cancer and antiviral chemotherapy
-
-
-
additional information
?
-
-
phosphorylates both pyrimidine and purine deoxynucleosides, including numerous nucleoside analogue anticancer and antiviral prodrugs
-
-
-
additional information
?
-
-
dCK phosphorylates all three natural deoxyribonucleosides, exhibiting the highest affinity for 2'-deoxycytidine
-
-
-
additional information
?
-
-
dCK interacts with cyclin-dependent kinase 1 (Cdk1) and the interaction inhibits Cdk1 activity both in vitro and in vivo
-
-
-
additional information
?
-
-
development and evaluation of a homogeneous fluorescence-based assay for real-time and simultaneous detection of thymidine kinase 1 and deoxycytidine kinase activities, detailed overview
-
-
-
additional information
?
-
-
1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)uracil is no substrate. But 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)cytosine can be converted to 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)uracil by cytidine deaminase
-
-
-
additional information
?
-
-
deoxycytidine kinase shows broad substrate specificity, catalyzing the phosphorylation of deoxycytidine, deoxyadenosine, and deoxyguanosine with ATP or UTP as phosphoryl donor
-
-
-
additional information
?
-
-
substrate specificity or wild-type an dmutant enzymes, overview
-
-
-
additional information
?
-
-
the human enzyme is not active with the acyclic guanine analogue acyclovir. Acyclovir binds at the dCK active site, but does so adopting a nonproductive conformation. Despite binding ACV, the enzyme remains in the open, inactive state, overview. dCK would phosphorylate acyclic guanine analogs if they can induce a similar rotation
-
-
-
additional information
?
-
Mus musculus C57BL/6J
-
1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)uracil is no substrate. But 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)cytosine can be converted to 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)uracil by cytidine deaminase
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + 2',2'-difluorodeoxycytidine
ADP + 2',2'-difluorodeoxycytidine monophosphate
show the reaction diagram
-
i.e. gemcitabine, transport and metabolism in vivo, overview
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
P43346
-
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides, supplying cells with deoxyribonucleotides for DNA replicative and repair synthesis
-
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
P27707
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
P43346
-
-
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
involved in nucleotide synthesis, involved in DNA repair
-
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides
-
-
?
ATP + 2'-deoxycytidine
ADP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides, supplying cells with deoxyribonucleotides for DNA replicative and repair synthesis
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
P43346
-
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides
-
-
?
ATP + 2-chlorodeoxyadenosine
ADP + 2-chlorodeoxyadenosine 5'-phosphate
show the reaction diagram
-
i.e. cladribine
-
-
?
ATP + 5-methyldeoxycytidine
ADP + 5-methyl-dCMP
show the reaction diagram
-
-
-
-
?
ATP + cladribine
ADP + phospho-cladribine
show the reaction diagram
-
-
-
-
?
ATP + clofarabine
ADP + phospho-clofarabine
show the reaction diagram
-
-
-
-
?
ATP + cytarabine
ADP + cytarabine 5'-phosphate
show the reaction diagram
-
drug against acute myeloid and lymphoblastic leukemia
-
-
?
ATP + deoxyadenosine
ADP + dAMP
show the reaction diagram
-
-
-
-
?
ATP + deoxyadenosine
ADP + dAMP
show the reaction diagram
-
-
-
-
?
ATP + deoxyadenosine
ADP + dAMP
show the reaction diagram
Mus musculus C57BL/6J
-
-
-
-
?
ATP + deoxycytidine
ADP + dCMP
show the reaction diagram
-
-
-
-
?
ATP + deoxycytidine
ADP + dCMP
show the reaction diagram
-
-
-
-
?
ATP + deoxycytidine
ADP + dCMP
show the reaction diagram
-
-
-
-
?
ATP + deoxycytidine
ADP + dCMP
show the reaction diagram
-
-
-
-
?
ATP + deoxycytidine
ADP + ?
show the reaction diagram
-
-
-
-
?
ATP + deoxycytidine
ADP + ?
show the reaction diagram
-
key enzyme in anabolic phosphorylation of deoxyribonucleosides and their analogues
-
-
?
ATP + deoxycytidine
ADP + ?
show the reaction diagram
-
key anabolic enzyme for activation of purine or pyrimidine deoxynucleosides as well as cytidine arabinoside and other anti-tumor drugs
-
-
?
ATP + deoxycytidine
ADP + dCMP
show the reaction diagram
Mus musculus C57BL/6J
-
-
-
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
-
-
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
-
-
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
Mus musculus C57BL/6J
-
-
-
-
?
ATP + fludarabine
ADP + phospho-fludarabine
show the reaction diagram
-
-
-
-
?
NTP + (-)-beta-2',3'-dideoxy-3'-thiacytidine
NDP + (-)-beta-2',3'-dideoxy-3'-thiacytidine 5'-phosphate
show the reaction diagram
-
activation of the clinically relevant substrate
-
-
?
NTP + 1-beta-D-arabinofuranosylcytosine
NDP + 1-beta-D-arabinofuranosylcytosine 5'-phosphate
show the reaction diagram
-
antineoplastic agent
-
-
?
NTP + 1-beta-D-arabinofuranosylcytosine
NDP + 1-beta-D-arabinofuranosylcytosine 5'-phosphate
show the reaction diagram
-
i.e. cytarabine, rate limiting enzyme in the activation of the prodrug
-
-
?
NTP + 1-beta-D-arabinosylcytosine
NDP + 1-beta-D-arabinosylcytosine 5'-phosphate
show the reaction diagram
-
i.e. cytaribine, activation of the pharmaceutically relevant substrate which is commonly used in the treatment of lymphoproliferative malignancies
-
-
?
NTP + 2',2'-difluorodeoxycytidine
NDP + 2',2'-difluorodeoxycytidine 5'-phosphate
show the reaction diagram
-
i.e. gemcitabine, activation of the pharmaceutically relevant substrate which is commonly used in the treatment of solid malignant tumors
-
-
?
NTP + 2',2'-difluorodeoxycytidine
NDP + 2',2'-difluorodeoxycytidine 5'-phosphate
show the reaction diagram
-
i.e. gemcitabine, rate limiting enzyme in the activation of the pharmaceutically relevant substrate which is commonly used in the treatment of solid malignant tumors
-
-
?
NTP + 2',2'-difluorodeoxycytidine
NDP + 2',2'-difluorodeoxycytidine 5'-phosphate
show the reaction diagram
-
i.e. gemcitabine, rate limiting enzyme in the activation of the pharmaceutically relevant substrate which is commonly used in the treatment of tumors
-
-
?
NTP + 2',2'-difluorodeoxycytidine
NDP + 2',2'-difluorodeoxycytidine 5'-phosphate
show the reaction diagram
-
substrate also termed gemcitabine
-
-
?
NTP + 2',3'-dideoxycytidine
NDP + 2',3'-dideoxycytidine 5'-phosphate
show the reaction diagram
-
antiviral agent
-
-
?
NTP + 2',3'-dideoxycytidine
NDP + 2',3'-dideoxycytidine 5'-phosphate
show the reaction diagram
-
i.e. zalcitabine, activation of the pharmaceutically relevant substrate which is used in the treatment of HIV infections
-
-
?
NTP + 2'-deoxy-3'-thiacytidine
NDP + 2'-deoxy-3'-thiacytidine 5'-phosphate
show the reaction diagram
-
antiviral agent
-
-
?
NTP + 2'-deoxy-3'-thiacytidine
NDP + 2'-deoxy-3'-thiacytidine 5'-phosphate
show the reaction diagram
-
i.e. lamivudine, activation of the pharmaceutically relevant substrate which is used in the treatment of HIV infections
-
-
?
NTP + 2'-deoxyadenosine
NDP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
NTP + 2'-deoxyadenosine
NDP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides
-
-
?
NTP + 2'-deoxycytidine
NDP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
more effective substrate than 2'-deoxyadenosine and 2'-deoxyguanosine
-
-
?
NTP + 2'-deoxycytidine
NDP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides
-
-
?
NTP + 2'-deoxyguanosine
NDP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
NTP + 2'-deoxyguanosine
NDP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides
-
-
?
NTP + 2-chloro-2'-deoxyadenosine
NDP + 2-chloro-2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
i.e. cladribine, activation of the pharmaceutically relevant substrate which is commonly used in the treatment of lymphoproliferative malignancies
-
-
?
NTP + 2-chloro-2'-deoxyadenosine
NDP + 2-chloro-2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
i.e. cladribine, antineoplastic agent
-
-
?
NTP + 2-chloro-2'-deoxyadenosine
NDP + 2-chloro-2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
phosphorylation of chemotherapeutically important nucleoside analogues
-
-
?
NTP + 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-9H-purin-6-amine
NDP + 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-9H-purin-6-amine 5'-phosphate
show the reaction diagram
-
i.e. clofarabine, rate-limiting step in the activation of the prodrug, precursor of an effective chemotherapeutic agent for leukemias and other haematological malignancies
-
-
?
NTP + 9-beta-D-arabinosyl 2-fluoroadenine
NDP + 9-beta-D-arabinosyl 2-fluoroadenine 5'-phosphate
show the reaction diagram
-
activation of the pharmaceutically relevant substrate which is commonly used in the treatment of lymphoproliferative malignancies
-
-
?
NTP + 9-beta-D-arabinosyl 2-fluoroadenine
NDP + 9-beta-D-arabinosyl 2-fluoroadenine 5'-phosphate
show the reaction diagram
-
i.e. fludarabine, activation of the pharmaceutically relevant substrate which is commonly used in the treatment of lymphoproliferative malignancies
-
-
?
NTP + 9-beta-D-arabinosyl-2-fluoroadenine
NDP + 9-beta-D-arabinosyl-2-fluoroadenine 5'-phosphate
show the reaction diagram
-
phosphorylation of chemotherapeutically important nucleoside analogues
-
-
?
NTP + deoxycytidine
NDP + dCMP
show the reaction diagram
-
-
-
-
?
NTP + troxacitabine
?
show the reaction diagram
-
activation of the clinically relevant substrate
-
-
?
UTP + 2',3'-dideoxycytidine
UDP + 2',3'-dideoxycytidine 5'-phosphate
show the reaction diagram
-
i.e. zalcitabine, activation of the pharmaceutically relevant substrate which is used for the treatment of HIV infections
-
-
?
UTP + 2'-deoxy-3'-thiacytidine
UDP + 2'-deoxy-3'-thiacytidine 5'-phosphate
show the reaction diagram
-
i.e. lamivudine, activation of the pharmaceutically relevant substrate which is used for the treatment of HIV infections
-
-
?
UTP + 2'-deoxyadenosine
UDP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
UTP + 2'-deoxyadenosine
UDP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides
-
-
?
UTP + 2'-deoxyadenosine
UDP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides, supplying cells with deoxyribonucleotides for DNA replicative and repair synthesis
-
-
?
UTP + 2'-deoxycytidine
UDP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
P27707
-
-
-
?
UTP + 2'-deoxycytidine
UDP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
-
-
-
?
UTP + 2'-deoxycytidine
UDP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
preferred donor and acceptor substrates
-
-
?
UTP + 2'-deoxycytidine
UDP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides
-
-
?
UTP + 2'-deoxycytidine
UDP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides, supplying cells with deoxyribonucleotides for DNA replicative and repair synthesis
-
-
?
UTP + 2'-deoxyguanosine
UDP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
UTP + 2'-deoxyguanosine
UDP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
rate-limiting reaction in the salvage of deoxyribonucleosides
-
-
?
UTP + cladribine
UDP + phospho-cladribine
show the reaction diagram
-
-
-
-
?
UTP + clofarabine
UDP + phospho-clofarabine
show the reaction diagram
-
-
-
-
?
UTP + deoxyadenosine
UDP + dAMP
show the reaction diagram
-
-
-
-
?
UTP + deoxycytidine
UDP + dCMP
show the reaction diagram
-
-
-
-
?
UTP + deoxycytidine
UDP + dCMP
show the reaction diagram
-
UTP is physiological phosphate donor
-
-
?
UTP + deoxyguanosine
UDP + dGMP
show the reaction diagram
-
-
-
-
?
UTP + fludarabine
UDP + phospho-fludarabine
show the reaction diagram
-
-
-
-
?
ATP + L-thymidine
?
show the reaction diagram
-
human dCK, in addition to being able to phosphorylate both purines and pyrimidines, has the special ability to accept L-nucleosides as substrates
-
-
?
additional information
?
-
-
5'-phosphorylation of is a crucial step in metabolic activation of anticancer and antiviral nucleoside antimetabolites, such as cladribine, gemcitabine, cytarabine, and lamivudine
-
-
-
additional information
?
-
-
de novo synthesis and salvage of ribonucleotides and deoxyribonucleotides, metabolism overview, enzyme is active and medically important in anticancer and antiviral therapy due to high phosphorylation activity of prodrugs, overview
-
-
-
additional information
?
-
-
enzyme is active and medically important in anticancer and antiviral therapy due to high phosphorylation activity of prodrugs, overview
-
-
-
additional information
?
-
-
resistance of cells to cytarabine is caused by dCK enzyme deficiency
-
-
-
additional information
?
-
-
the activation of the enzyme is a first step in 2-chloro-2'-deoxyadenosine-induced cytotoxicity
-
-
-
additional information
?
-
-
the earliest nucleotide kinase in evolution, probably encoded by the so-called dCK/dGK/TK2-like gene, is the progenitor gene, several duplications of it are the reason for evolutionary occurrence of nucleoside kinases with strict substrate specificities in other organism, phylogenetic tree, overview
-
-
-
additional information
?
-
P43346
the earliest nucleotide kinase in evolution, probably encoded by the so-called dCK/dGK/TK2-like gene, is the progenitor gene, several duplications of it are the reason for evolutionary occurrence of nucleoside kinases with strict substrate specificities in other organism, phylogenetic tree, overview
-
-
-
additional information
?
-
-
the enzyme is active and important in activation of several clinically important deoxynucleoside analogues used for the treatment of haematological and solid malignancies
-
-
-
additional information
?
-
-
catalyzes the rate-limiting step of the deoxyribonucleoside salvage pathway, key role in the activation of numerous nucleoside analogues used in anti-cancer and antiviral chemotherapy
-
-
-
additional information
?
-
-
dCK is able to phosphorylate both D- and L-nucleosides and nucleoside analogs
-
-
-
additional information
?
-
-
enzyme of the salvage pathway for deoxyribonucleotide synthesis, which provides resting cells with deoxynucleotides for DNA repair and mitochondrial DNA synthesis, important enzyme for the phosphorylation/activation of deoxynucleoside analogues, which are cytotoxic towards both replicating and indolent malignancies
-
-
-
additional information
?
-
-
essential for the synthesis of deoxynucleotides required for DNA repair and involved in deoxynucleoside analogue activation
-
-
-
additional information
?
-
-
key enzyme in the deoxynucleoside salvage pathway and in the activation of numerous nucleoside analogues used in cancer and antiviral chemotherapy
-
-
-
additional information
?
-
-
phosphorylates both pyrimidine and purine deoxynucleosides, including numerous nucleoside analogue anticancer and antiviral prodrugs
-
-
-
additional information
?
-
-
dCK phosphorylates all three natural deoxyribonucleosides, exhibiting the highest affinity for 2'-deoxycytidine
-
-
-
additional information
?
-
-
dCK interacts with cyclin-dependent kinase 1 (Cdk1) and the interaction inhibits Cdk1 activity both in vitro and in vivo
-
-
-
additional information
?
-
-
development and evaluation of a homogeneous fluorescence-based assay for real-time and simultaneous detection of thymidine kinase 1 and deoxycytidine kinase activities, detailed overview
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
UTP
-
preferred phosphate donor
UTP
-
preferred, in vivo important phoaphate donor
UTP
-
preferred phosphoryl group donor
additional information
-
enzyme lalso utilizes other nucleoside triphosphates as phosphate donors
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
-
activation; can replace Mn2+ or Mg2+ to some extent
Ca2+
-
activation; can replace Mn2+ or Mg2+ to some extent
Ca2+
-
about 55% as efficient as Mg2+; activation
Ca2+
-
activation
Ca2+
-
activation
CdCl2
-
activation, in the absence of dithiothreitol
Co2+
-
about 40% as efficient as Mg2+; activation
Co2+
-
activation
Co2+
-
about 30% as efficient as Mg2+; activation
Fe2+
-
activation; can replace Mn2+ or Mg2+ to some extent
Fe2+
-
about 45% as efficient as Mg2+; activation
Fe2+
-
activation
Fe2+
-
about 60% as efficient as Mg2+; activation
Mg2+
-
requirement, 2 mM
Mg2+
-
more efficient than Mn2+ or Ca2+
Mg2+
-
Mg2+/ATP complex is the reactive species
Mg2+
-
below: decrease of activity; maximal activity at a ATP:Mg2+-ratio of 1:1; Mg2+/ATP complex is the reactive species
Mg2+
-
maximal activity at a ATP:Mg2+-ratio of 1:1; Mg2+/ATP complex is the reactive species
Mg2+
-
Mg2+/ATP complex is the reactive species
Mg2+
-
in complex with ATP
Mg2+
-
in complex with ATP or UTP
Mg2+
-
required
Mg2+
-
required
Mn2+
-
0.5 mM; requirement
Mn2+
-
about 80% as efficient as Mg2+; requirement
Mn2+
-
requirement
Ni2+
-
about 20% as efficient as Mg2+; activation
Ni2+
-
activation
Ni2+
-
not
Sr2+
-
about 15% as efficient as Mg2+; activation
Sr2+
-
activation
Zn2+
-
not
Zn2+
-
about 40% as efficient as Mg2+; activation
Zn2+
-
activation
Zn2+
-
about 30% as efficient as Mg2+; activation
Mn2+
-
about 90% as efficient as Mg2+; requirement
additional information
-
no activation by Ba2+, Cu2+
additional information
-
no activation by Ba2+, Cu2+
additional information
-
no activation by Ba2+, Cu2+; no activation by monovalent cations
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2'-deoxy-5-fluorocytidine
-
-
2'-deoxycytidine
-
-
2'-O-methylcytidine
-
-
2-(2-[1-[6-(1-benzothiophen-2-yl)pyrimidin-4-yl]piperidin-4-yl]ethoxy)-5-fluoropyrimidin-4-amine
-
-
2-([1-[6-(1-benzothiophen-2-yl)pyrimidin-4-yl]piperidin-4-yl]methoxy)-5-fluoropyrimidin-4-amine
-
-
2-([1-[6-(1-benzothiophen-2-yl)pyrimidin-4-yl]piperidin-4-yl]oxy)-5-fluoropyrimidin-4-amine
-
-
2-([1-[6-(2-chlorophenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy)-5-fluoropyrimidin-4-amine
-
-
2-([1-[6-(2-ethylphenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy)-5-fluoropyrimidin-4-amine
-
-
2-([1-[6-(3-chlorophenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy)-5-fluoropyrimidin-4-amine
-
-
2-([1-[6-(4-chloro-2-methylphenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy)-5-fluoropyrimidin-4-amine
-
-
2-([1-[6-(4-chlorophenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy)-5-fluoropyrimidin-4-amine
-
-
2-([1-[6-(biphenyl-2-yloxy)pyrimidin-4-yl]piperidin-4-yl]oxy)-5-fluoropyrimidin-4-amine
-
-
2-([6-[4-(4-amino-2-oxopyrimidin-1(2H)-yl)piperidin-1-yl]-5-fluoropyrimidin-4-yl]oxy)benzonitrile
-
-
2-chloroadenosine
-
-
2-[(6-[4-[(4-amino-5-fluoropyrimidin-2-yl)oxy]piperidin-1-yl]-2-bromopyrimidin-4-yl)oxy]benzonitrile
-
-
2-[(6-[4-[(4-amino-5-fluoropyrimidin-2-yl)oxy]piperidin-1-yl]-2-methylpyrimidin-4-yl)oxy]benzonitrile
-
-
2-[(6-[4-[(4-amino-5-fluoropyrimidin-2-yl)oxy]piperidin-1-yl]-5-fluoropyrimidin-4-yl)oxy]-5-methoxybenzonitrile
-
-
2-[(6-[4-[(4-amino-5-fluoropyrimidin-2-yl)oxy]piperidin-1-yl]-5-fluoropyrimidin-4-yl)oxy]benzonitrile
-
-
2-[(6-[4-[(4-amino-5-fluoropyrimidin-2-yl)oxy]piperidin-1-yl]-5-methylpyrimidin-4-yl)oxy]benzonitrile
-
-
2-[(6-[4-[(4-amino-5-fluoropyrimidin-2-yl)oxy]piperidin-1-yl]pyrimidin-4-yl)oxy]-5-methoxybenzonitrile
-
-
2-[(6-[4-[(4-amino-5-fluoropyrimidin-2-yl)oxy]piperidin-1-yl]pyrimidin-4-yl)oxy]benzonitrile
-
-
2-[(6-[4-[(4-aminopyrimidin-2-yl)oxy]piperidin-1-yl]-5-fluoropyrimidin-4-yl)oxy]benzonitrile
-
-
2-[[6-(1-benzothiophen-2-yl)pyrimidin-4-yl]oxy]-5-fluoropyrimidin-4-amine
-
-
3'-O-methyl-2'deoxycytidine
-
-
3'-[[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]sulfamoyl]biphenyl-4-carboxamide
-
-
3-[(6-[4-[(4-amino-5-fluoropyrimidin-2-yl)oxy]piperidin-1-yl]-2-fluoropyrimidin-4-yl)oxy]-4-methoxybenzonitrile
-
-
3-[(6-[4-[(4-amino-5-fluoropyrimidin-2-yl)oxy]piperidin-1-yl]-5-fluoropyrimidin-4-yl)oxy]-4-methoxybenzonitrile
-
-
3-[(6-[4-[(4-amino-5-fluoropyrimidin-2-yl)oxy]piperidin-1-yl]-5-fluoropyrimidin-4-yl)oxy]benzonitrile
-
-
3-[(6-[4-[(4-amino-5-fluoropyrimidin-2-yl)oxy]piperidin-1-yl]pyrimidin-4-yl)oxy]benzonitrile
-
-
4'-thio-beta-D-arabinofuranosylcytosine
-
IC50 0.000024 mM
4-(1-benzothiophen-2-yl)-6-[4-(2-oxo-2-pyrrolidin-1-ylethyl)piperazin-1-yl]pyrimidine
-
-
4-(1-benzothiophen-2-yl)-6-[4-(2-oxo-2-pyrrolidin-1-ylethyl)piperazin-1-yl]pyrimidine
-
-
5'-O-ethyl-2'-deoxycytidine
-
-
5'-O-methyl-2'-deoxycytidine
-
-
5-chloro-4'-thio-beta-D-arabinofuranosylcytosine
-
IC50 0.051 mM
5-Fluoro-2'-deoxycytidine
-
-
5-Fluoro-2'-deoxycytidine
-
competitive inhibitor
5-fluoro-2-([1-[5-fluoro-6-(4-methoxyphenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy)pyrimidin-4-amine
-
-
5-fluoro-2-([1-[6-(2-fluorophenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy)pyrimidin-4-amine
-
-
5-fluoro-2-([1-[6-(2-methoxyphenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy)pyrimidin-4-amine
-
-
5-fluoro-2-([1-[6-(2-methylphenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy)pyrimidin-4-amine
-
-
5-fluoro-2-([1-[6-(3-methoxyphenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy)pyrimidin-4-amine
-
-
5-fluoro-2-([1-[6-(4-methoxyphenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy)pyrimidin-4-amine
-
-
5-fluoro-2-([1-[6-(4-methylphenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy)pyrimidin-4-amine
-
-
5-fluoro-2-[[1-(6-phenoxypyrimidin-4-yl)piperidin-4-yl]oxy]pyrimidin-4-amine
-
-
5-fluoro-4'-thio-beta-D-arabinofuranosylcytosine
-
IC50 0.0000020 mM
adenosine arabinoside
-
weak, not with deoxyadenosine as substrate
alpha-D-2'-Deoxythioguanosine
-
-
CDP
-
strong
CTP
-
strong, ATP as substrate
cytidine
-
weak
cytidine
-
not
cytidine
-
cytosine arabinoside as substrate
cytidine
-
not
cytidine
-
alpha-isomer
cytidine
-
deoxycytidine as substrate
cytosine arabinoside
-
ATP as substrate; deoxycytidine as substrate; strong, deoxyadenosine as substrate
cytosine arabinoside
-
deoxycytidine as substrate
cytosine arabinoside
-
deoxycytidine as substrate
cytosine arabinoside
-
deoxyguanosine as substrate
cytosine arabinoside
-
deoxycytidine as substrate
cytosine arabinoside
-
IC50 0.0000055 mM
Cytosine arabinoside monophosphate
-
strong
Cytosine arabinoside triphosphate
-
strong
Cytosine arabinoside triphosphate
-
-
Cytosine arabinoside triphosphate
-
weak
dADP
-
strong
dAMP
-
strong
dATP
-
strong
dCDP
-
strong, ATP as substrate
dCMP
-
ATP as substrate; product inhibition, strong
dCMP
-
dTTP reverses; product inhibition, strong
dCMP
-
only cytosolic isozyme I; product inhibition, strong
dCMP
-
product inhibition, strong
dCTP
-
strong, pH-dependent
dCTP
-
reversible by dTTP; reversible by UTP, dUTP
dCTP
-
kinetics; reversible by dTTP; reversible by UDP
dCTP
-
ATP as substrate
dCTP
-
no reversion by beta-gamma-methylene diphosphonate analogue of dTTP
dCTP
-
cytosine arabinoside as substrate; isozyme II
dCTP
-
no inhibition at physiological concentrations
dCTP
-
cytosine arabinoside as substrate
dCTP
-
ATP as substrate; moderate phosphate donor in the absence of ATP
dCTP
-
at 0.013 mM, substrates ATP, deoxycytosine, 30% inhibition
dCTP
-
at 0.013 mM, substrates ATP, deoxycytosine, 50% inhibition
dCTP
-
feedback inhibition, competitive versus phosphate donors
dCTP
-
feedback inhibition
dCTP
-
a potent inhibitor of the enzyme when ATP is the phosphoryl donor, but a relatively weak inhibitor when the enzyme activity is measured with UTP as the phosphoryl donor. Inhibition is higher with respect to cladribine than deoxycytidine
deoxyadenosine
-
-
deoxyadenosine
-
not
deoxyadenosine
-
cytosine arabinoside or deoxyguanosine as substrate
deoxyadenosine
-
cytosolic isozyme I, weak
deoxyadenosine
-
deoxycytidine
deoxyadenosine
-
cytosolic isozyme I, weak; deoxycytidine; kinetics
Deoxycytidine
-
deoxyadenosine as substrate
Deoxycytidine
-
cytosine arabinoside as substrate
Deoxycytidine
-
cytosine arabinoside as substrate; deoxyadenosine as substrate; deoxyguanosine as substrate
Deoxycytidine
-
cytidine as substrate; deoxyguanosine as substrate
Deoxycytidine
-
deoxyadenosine as substrate; deoxyguanosine as substrate
Deoxycytidine
-
cytosine arabinoside as substrate
Deoxycytidine
-
at concentrations greater than 0.003 mM, UTP as substrate, noncompetitive
deoxyguanosine
-
cytosine arabinoside as substrate
deoxyguanosine
-
not
deoxyguanosine
-
deoxyguanosine as substrate, cytosolic isozyme I, weak
deoxyguanosine
-
deoxycytidine as substrate
deoxythymidine
-
cytosolic isozyme I, not
deoxythymidine
-
weak
dGDP
-
strong
dGMP
-
strong
dGTP
-
ATP as substrate
dGTP
-
ATP as substrate
Dideoxyadenosine
-
-
Dideoxycytidine
-
-
Dinitrophenol
-
weak
dTDP
-
strong
dTTP
-
ATP as substrate; weak
dTTP
-
at increased deoxycytidine concentrations
dTTP
-
only mitochondrial isozyme; strong
dTTP
-
ATP as substrate; weak
dUDP
-
strong
dUDP
-
only cytosolic isozyme I; strong
dUMP
-
strong
GSSG
-
thiol reagents protect or reverse
GTP
-
not, deoxyadenosine as substrate; weak, ATP and deoxycytidine as substrate
GTP
-
not, deoxyadenosine as substrate
H-7
-
reduces the enzyme activation caused by the addition of 2-chloro-2-deoxyadenosine
HgCl2
-
strong, thiol reagents protect
lambda protein phosphatase
-
-
-
LP-375752
-
i.e. 2-[4-(6-benzo[b]thiophen-2-yl-pyrimidin-4-yl)-piperazin-1-yl]-1-pyrrolidin-1-yl-ethanone
N-ethylmaleimide
-
weak
N-ethylmaleimide
-
thiol reagents protect or reverse
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-2',4'-dichlorobiphenyl-3-sulfonamide
-
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-2'-chlorobiphenyl-3-sulfonamide
-
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-3'-chlorobiphenyl-3-carboxamide
-
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-3'-chlorobiphenyl-3-sulfonamide
-
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-3-bromobenzenesulfonamide
-
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4''-chloro-2''-methyl-1,1':4',1''-terphenyl-3-carboxamide
-
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4''-chloro-2''-methyl-1,1':4',1''-terphenyl-3-sulfonamide
-
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-(methylsulfonyl)biphenyl-3-sulfonamide
-
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-chlorobiphenyl-3-sulfonamide
-
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-cyanobiphenyl-3-sulfonamide
-
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-formylbiphenyl-3-sulfonamide
-
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-methoxybiphenyl-3-carboxamide
-
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-methoxybiphenyl-3-sulfonamide
-
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-methylbiphenyl-3-sulfonamide
-
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4-(1-benzothiophen-2-yl)pyridine-2-carboxamide
-
potent, selective, and orally bioavailable inhibitor of dCK
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4-bromobenzenesulfonamide
-
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4-nitrobenzenesulfonamide
-
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]benzenesulfonamide
-
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]biphenyl-3-carboxamide
-
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]biphenyl-3-sulfonamide
-
-
N6-Phenyladenosine
-
-
NaCl
-
at 0.2-0.4 M, stimulation of 2-deoxycytidine and 2-chlorodeoxyadenosine phosphorylation, but inhibition of 2-deoxyguanosine phosphorylation
Non-substrate inhibitors
-
-
-
Nucleoside analogs
-
related to deoxycytidine, deoxyadenosine or deoxyguanosine
Nucleosides
-
overview, ATP and deoxyadenosine or deoxycytidine as substrate
Nucleosides
-
-
p-chloromercuribenzoate
-
thiol reagents protect or reverse
P1,P4-diadenosine 5'-tetraphosphate
-
not di-, tri- or pentaphosphate derivative
protein phosphatase lambda
-
-
-
Sodium diphosphate
-
not monophosphate
staurosporine
-
reduces the enzyme activation caused by the addition of 2-chloro-2-deoxyadenosine
Substrate derivatives
-
overview
-
suramin
-
no effect in unirradiated cells, complete abolishment of UV-C light induced activation
tetrahydrouridine
-
-
Tris-maleate buffer
-
-
Trypsin
-
substrates or dNTP protect corresponding active site
-
UDP
-
strong
UDP
-
only cytosolic isozyme I; strong
Uridine arabinoside
-
weak, cytosolic isozyme I
UTP
-
ATP as substrate; not with deoxyadenosine as substrate
UTP
-
not mitochondrial isozyme
LP-503392
-
i.e. 2-thio-2'-deoxycytidine
additional information
-
little or no inhibition by AMP, dTMP, adenosine, guanosine
-
additional information
-
little or no inhibition by deoxyuridine; no inhibition by TTP; no inhibition by uridine, thymidine; relatively insensitive to SH-inhibitors and detergents
-
additional information
-
little or no inhibition by AMP, dTMP, adenosine, guanosine; little or no inhibition by deoxyuridine
-
additional information
-
no inhibition by ribavirin
-
additional information
-
deoxycytidine phosphorylating ability shows different inhibition pattern than deoxyadenosine activity
-
additional information
-
little or no inhibition by AMP, dTMP, adenosine, guanosine; little or no inhibition by deoxyuridine; little or no inhibition by ribavirin; no inhibition by inosine, xanthosine, S-adenosylhomocysteine, S-adenosylmethionine; no inhibition by uridine, thymidine; overview
-
additional information
-
activity of enzyme is reduced by hyperosmotic treatment of cells
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1-beta-D-arabinosylcytosine
-
i.e. cytarabine, 0.001 mM, stimulation
2'-deoxyadenosine/deoxycoformycin
-
no stimulation of enzyme activity by either compound if applied alone, with both compound at 0.01 mM 2.4fold activation occurs
-
2'-deoxythymidine-5'-thiosulphate
-
in intact cells, activation, reversed by 2-deoxycytidine
2-chloro-2'-arabino-fluoro-2'-deoxyadenosine
-
0.001 mM, stimulation
2-chloro-2'-deoxy-2'-fluoro-arabinosyladenine
-
stimulation
2-chloro-2'-deoxyadenosine
-
i.e. cladribine, 0.001 mM, stimulation
2-chloro-2'-deoxyadenosine
-
up to 0.01 mM, up to 4fold increase in activity
2-chloro-2'-deoxyadenosine
-
2.4fold activation at 0.003 mM, activation is slightly inhibited by 3-aminobenzamide, the activation of the enzyme is a first step in 2-chloro-2'-deoxyadenosine-induced cytotoxicity
2-chloro-2'-deoxyadenosine
-
-
2-chloro-2'-deoxyadenosine
-
increases activity by increasing phosphorylation of Ser74
2-fluoro-1-beta-D-arabinosyladenine
-
i.e. fludarabine, 0.001 mM, stimulation
ABCG2
-
the ABC transporter activates the enzyme and reduces intracellular accumulation of clofarabine
-
Aphidicolin
-
at 0.006-0.012 mM, 2-3fold activation
Aphidicolin
-
increases activity by increasing phosphorylation of Ser74
Aphidicolin
-
increases dCK activity via Ser74 phosphorylation, effect of aphidicolin treatment on dCK activity in leukemic cells with substrate deoxycytidine and cladribine and other substrates, overview
arabinosylcytidine
-
stimulation
ATP
-
substrate activation, at high concentrations of deoxycytidine
Bovine serum albumin
-
activation
-
calyculin A
-
inhibitor of protein phosphatases, activation
CHAPS
-
slight stimulation, deoxycytidine as substrate
deoxyadenosine
-
activation, deoxycytidine as substrate, mitochondrial isozyme
deoxyguanosine
-
activation, deoxycytidine as substrate, mitochondrial isozyme
dithiothreitol
-
not
dithiothreitol
-
activation
dithiothreitol
-
activation
dithiothreitol
-
activation
etoposide
-
0.001 mM, stimulation
etoposide
-
increases activity by increasing phosphorylation of Ser74
gamma-radiation
-
0.5-2 GY dosage, activation
-
genistein
-
-
NaCl
-
at 0.2-0.4 M, stimulation of 2-deoxycytidine and 2-chlorodeoxyadenosine phosphorylation, but inhibition of 2-deoxyguanosine phosphorylation
NaF
-
15 mM, 1 h, activity about twice as high as initial level
okadaic acid
-
-
paclitaxel
-
paclitaxel increases dCK (10% to 50%) activity
PD 153035
-
i.e. 4-(3-bromoanilino)-6,7-dimethoxy-quinazinoline
PD 98059
-
i.e. 2'-amino-3'-methoxyflavone, in absence of deoxycytidine
SB 203580
-
in absence of deoxycytidine
Sodium cholate
-
slight stimulation, deoxycytidine as substrate
TTP
-
stimulation, cytosolic isozyme I
tyrphostin A47
-
-
UDP
-
stimulation, mitochondrial isozyme
Uridine arabinoside
-
activation, deoxycytidine as substrate, mitochondrial isozyme
Zwittergent 3-14
-
slight stimulation, deoxycytidine as substrate
genistein
-
increases activity by increasing phosphorylation of Ser74
additional information
-
not activating: 2-chloro-riboadenosine
-
additional information
-
enzyme is activated by inhibitors of signal transduction enzymes, overview, deoxycytidine prevents activation of the enzyme, no activation by PD 98059 and SB 203580 in presence of deoxycytidine
-
additional information
-
2- to 3-fold activation of enzyme by UV-C light irradiation
-
additional information
-
enzyme protein level increases when cells are incubated with cyclopentenyl cytosine
-
additional information
-
UV-C irradiation increases activity by increasing phosphorylation of Ser74
-
additional information
-
irradiation of intact cells increases enzyme activity, upregulation of activity might be caused by phosphorylation
-
additional information
-
the enzyme is activated in response to DNA damage. The ataxia-telangiectasia-mutated (ATM) kinase phosphorylates dCK on Serine 74 to activate it in response to DNA damage
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.003
-
(-)-beta-2',3'-dideoxy-3'-thiacytidine
-
wild type enzyme with ATP as phosphate donor, 37C, pH 7.5
0.008
-
(-)-beta-2',3'-dideoxy-3'-thiacytidine
-
C9S/C45S/C59S/C146S mutant enzyme with ATP as phosphate donor, 37C, pH 7.5; wild type enzyme with UTP as phosphate donor, 37C, pH 7.5
0.015
-
(-)-beta-2',3'-dideoxy-3'-thiacytidine
-
C9S/C45S/C59S/C146S mutant enzyme with UTP as phosphate donor, 37C, pH 7.5
0.00076
-
1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)cytosine
-
pH 7.6, 37C, recombinant enzyme
0.00654
-
1-(2'-deoxy-2'-fluoro-beta-L-arabinofuranosyl)-5-bromocytosine
-
pH 7.6, 37C, recombinant enzyme
0.00061
-
1-(2'-deoxy-2'-fluoro-beta-L-arabinofuranosyl)-5-chlorocytosine
-
pH 7.6, 37C, recombinant enzyme
0.00102
-
1-(2'-deoxy-2'-fluoro-beta-L-arabinofuranosyl)-5-methylcytosine
-
pH 7.6, 37C, recombinant enzyme
0.003
-
1-beta-D-arabinofuranosylcytosine
-
residues 65-79 deletion mutant with UTP as cosubstrate; wild type enzyme with UTP as cosubstrate
0.0059
-
1-beta-D-arabinofuranosylcytosine
-
wild-type, pH 7.5, 25C
0.007
-
1-beta-D-arabinofuranosylcytosine
-
wild type enzyme with ATP as cosubstrate
0.013
-
1-beta-D-arabinofuranosylcytosine
-
residues 65-79 deletion mutant with ATP as cosubstrate
0.024
-
1-beta-D-arabinofuranosylcytosine
-
mutant S74E, pH 7.5, 25C
0.0131
-
1-beta-D-arabinosylcytosine
-
wild type enzyme, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
0.0506
-
1-beta-D-arabinosylcytosine
-
mutant enzyme R104L/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
0.1365
-
1-beta-D-arabinosylcytosine
-
mutant enzyme R104M/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
0.0062
-
2',2'-difluorodeoxycytidine
-
wild-type, pH 7.5, 25C
0.0146
-
2',2'-difluorodeoxycytidine
-
wild-type
0.015
-
2',2'-difluorodeoxycytidine
-
mutant S74E, pH 7.5, 25C
0.15
-
2',3'-dideoxycytidine
-
cosubstrate UTP, 37C, pH 7.6
0.23
-
2',3'-dideoxycytidine
-
cosubstrate ATP, 37C, pH 7.6
0.48
-
2',3'-dideoxycytidine
-
cosubstrate UTP, 37C, pH 7.6
0.67
-
2',3'-dideoxycytidine
-
cosubstrate ATP, 37C, pH 7.6
0.0085
-
2'-deoxyadenosine
-
cosubstrate UTP, pH 7.5, 37C
0.013
-
2'-deoxyadenosine
-
wild type enzyme with UTP as cosubstrate
0.019
-
2'-deoxyadenosine
-
cosubstrate UTP, 37C, pH 7.6
0.053
-
2'-deoxyadenosine
-
residues 65-79 deletion mutant with UTP as cosubstrate
0.081
-
2'-deoxyadenosine
-
wild-type, pH 7.5, 30C; wild-type, pH 7.5, 37C
0.091
-
2'-deoxyadenosine
-
mutant D47E/R104Q/D133G/N163I/F242L, pH 7.5, 30C
0.1
-
2'-deoxyadenosine
-
wild type enzyme with ATP as cosubstrate
0.1146
-
2'-deoxyadenosine
-
wild type enzyme, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
0.115
-
2'-deoxyadenosine
-
cosubstrate ATP, pH 7.5, 37C
0.1169
-
2'-deoxyadenosine
-
wild-type, pH 7.5, 25C
0.15
-
2'-deoxyadenosine
-
cosubstrate UTP, 37C, pH 7.6
0.1623
-
2'-deoxyadenosine
-
mutant enzyme R104L/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
0.231
-
2'-deoxyadenosine
-
mutant R104Q/D133G, pH 7.5, 30C
0.398
-
2'-deoxyadenosine
-
mutant R104M/D133S, pH 7.5, 37C
0.412
-
2'-deoxyadenosine
-
mutant R104M/D133A, pH 7.5, 37C
0.415
-
2'-deoxyadenosine
-
residues 65-79 deletion mutant with ATP as cosubstrate
0.452
-
2'-deoxyadenosine
-
mutant R104M/D133N, pH 7.5, 37C
0.48
-
2'-deoxyadenosine
-
cosubstrate ATP, 37C, pH 7.6
0.518
-
2'-deoxyadenosine
-
mutant S74E, pH 7.5, 25C
0.532
-
2'-deoxyadenosine
-
mutant R104Q/D133N, pH 7.5, 30C
0.55
-
2'-deoxyadenosine
-
cosubstrate ATP, 37C, pH 7.6
0.598
-
2'-deoxyadenosine
-
mutant A100V/R104M/D133A, pH 7.5, 37C
0.691
-
2'-deoxyadenosine
-
mutant R104M/D133T, pH 7.5, 37C
0.843
-
2'-deoxyadenosine
-
mutant A100V/R104M/D133S, pH 7.5, 37C
1.04
-
2'-deoxyadenosine
-
mutant enzyme R104M/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
1.437
-
2'-deoxyadenosine
-
mutant A100V/R104M/D133T, pH 7.5, 37C
0.00005
-
2'-deoxycytidine
-
cosubstrate UTP, 37C, pH 7.6
0.0001
-
2'-deoxycytidine
-
cosubstrate UTP, 37C, pH 7.6
0.00016
-
2'-deoxycytidine
-
cosubstrate ATP, 37C, pH 7.6
0.00016
-
2'-deoxycytidine
-
with ATP as cosubstrate
0.00018
-
2'-deoxycytidine
-
cosubstrate ATP, 37C, pH 7.6
0.001
-
2'-deoxycytidine
-
pH 7.6, 37C, recombinant enzyme
0.001
-
2'-deoxycytidine
-
less than 0.001 mM, residues 65-79 deletion mutant with UTP as cosubstrate; less than 0.001 mM, wild type enzyme with ATP as cosubstrate; less than 0.001 mM, wild type enzyme with UTP as cosubstrate
0.001
-
2'-deoxycytidine
-
-
0.0014
-
2'-deoxycytidine
-
residues 65-79 deletion mutant with ATP as cosubstrate
0.0017
-
2'-deoxycytidine
-
wild-type, pH 7.5, 25C
0.003
-
2'-deoxycytidine
-
Km below 0.003 mM, wild type enzyme, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
0.0057
-
2'-deoxycytidine
-
mutant enzyme R104M/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
0.008
-
2'-deoxycytidine
-
mutant enzyme R104L/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
0.0089
-
2'-deoxycytidine
-
mutant S74E, pH 7.5, 25C
0.021
-
2'-deoxyguanosine
-
wild type enzyme with UTP as cosubstrate
0.041
-
2'-deoxyguanosine
-
cosubstrate UTP, pH 7.5, 37C
0.079
-
2'-deoxyguanosine
-
mutant D47E/R104Q/D133G/N163I/F242L, pH 7.5, 30C
0.081
-
2'-deoxyguanosine
-
mutant R104Q/D133G, pH 7.5, 30C
0.087
-
2'-deoxyguanosine
-
residues 65-79 deletion mutant with UTP as cosubstrate
0.154
-
2'-deoxyguanosine
-
wild-type, pH 7.5, 37C
0.155
-
2'-deoxyguanosine
-
wild-type, pH 7.5, 30C
0.181
-
2'-deoxyguanosine
-
cosubstrate ATP, pH 7.5, 37C
0.231
-
2'-deoxyguanosine
-
wild type enzyme with ATP as cosubstrate
0.231
-
2'-deoxyguanosine
-
wild type enzyme, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
0.24
-
2'-deoxyguanosine
-
mutant R104Q/D133N, pH 7.5, 30C
0.2458
-
2'-deoxyguanosine
-
wild-type, pH 7.5, 25C
0.324
-
2'-deoxyguanosine
-
mutant R104M/D133N, pH 7.5, 37C
0.474
-
2'-deoxyguanosine
-
residues 65-79 deletion mutant with ATP as cosubstrate
0.602
-
2'-deoxyguanosine
-
mutant S74E, pH 7.5, 25C
0.739
-
2'-deoxyguanosine
-
mutant A100V/R104M/D133S, pH 7.5, 37C
1.164
-
2'-deoxyguanosine
-
mutant A100V/R104M/D133T, pH 7.5, 37C
1.172
-
2'-deoxyguanosine
-
mutant R104M/D133S, pH 7.5, 37C
1.203
-
2'-deoxyguanosine
-
mutant R104M/D133T, pH 7.5, 37C
1.28
-
2'-deoxyguanosine
-
mutant R104M/D133A, pH 7.5, 37C
1.364
-
2'-deoxyguanosine
-
mutant A100V/R104M/D133A, pH 7.5, 37C
1.865
-
2'-deoxyguanosine
-
mutant enzyme R104M/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
2.266
-
2'-deoxyguanosine
-
mutant enzyme R104L/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
0.0013
-
2,5-difluoro-4-[1-(2-deoxy-beta-L-ribofuranosyl)]-aniline
-
pH 7.6, 37C, recombinant enzyme
0.00099
-
2-chloro-2'-deoxyadenosine
-
cosubstrate UTP, 37C, pH 7.6
0.004
-
2-chloro-2'-deoxyadenosine
-
A119G mutant enzyme, 37C, pH 7.4; P122S mutant enzyme, 37C, pH 7.4
0.006
-
2-chloro-2'-deoxyadenosine
-
wild type enzyme, 37C, pH 7.4
0.0063
-
2-chloro-2'-deoxyadenosine
-
cosubstrate UTP, 37C, pH 7.6
0.009
-
2-chloro-2'-deoxyadenosine
-
I24V mutant enzyme, 37C, pH 7.4
0.017
-
2-chloro-2'-deoxyadenosine
-
cosubstrate ATP, 37C, pH 7.6
0.024
-
2-chloro-2'-deoxyadenosine
-
cosubstrate ATP, 37C, pH 7.6
0.0051
-
2-chlorodeoxyadenosine
-
cosubstrate UTP, pH 7.5, 37C
0.078
-
2-chlorodeoxyadenosine
-
cosubstrate ATP, pH 7.5, 37C
0.00032
-
4'-thio-2'-deoxycytidine
-
cosubstrate ATP 37C, pH 8.0
0.02
-
4'-thio-beta-D-arabinofuranosylcytosine
-
cosubstrate UTP 37C, pH 8.0
0.088
-
4'-thio-beta-D-arabinofuranosylcytosine
-
cosubstrate ATP 37C, pH 8.0
2
-
9-beta-D-arabinofuranosylguanine
-
cosubstrate UTP, 37C, pH 7.6
3
-
9-beta-D-arabinofuranosylguanine
-
cosubstrate ATP, 37C, pH 7.6
3
-
9-beta-D-arabinofuranosylguanine
-
cosubstrate UTP, 37C, pH 7.6
5
-
9-beta-D-arabinofuranosylguanine
-
cosubstrate ATP, 37C, pH 7.6
0.001
-
ATP
-
cosubstrate 2'-deoxycytidine, 37C, pH 7.4
0.0029
-
ATP
-
residues 65-79 deletion mutant with 2'-deoxycytidine as cosubstrate
0.0034
-
ATP
-
cosubstrate (-)-beta-2',3'-dideoxy-3'-thiacytidine, wild-type, 37C, pH 7.5
0.0035
-
ATP
-
wild type enzyme with 2'-deoxycytidine as cosubstrate
0.0084
-
ATP
-
cosubstrate (-)-beta-2',3'-dideoxy-3'-thiacytidine, mutant C9S/C45S/C59S/C146S, 37C, pH 7.5
0.0132
-
ATP
-
cosubstrate troxacitabine, wild-type, 37C, pH 7.5
0.019
-
ATP
-
wild type enzyme with 2'-deoxycytidine as phosphate acceptor, pH 7.6
0.025
-
ATP
-
C185A mutant enzyme with 2'-deoxycytidine as phosphate acceptor, pH 7.6
0.053
-
ATP
-
residues 65-79 deletion mutant with 1-beta-D-arabinofuranosylcytosine as cosubstrate
0.0568
-
ATP
-
cosubstrate troxacitabine, mutant C9S/C45S/C59S/C146S, 37C, pH 7.5
0.087
-
ATP
-
C185A mutant enzyme with 2'-deoxyadenosine as phosphate acceptor, pH 7.6
0.093
-
ATP
-
wild type enzyme with 1-beta-D-arabinofuranosylcytosine as cosubstrate
0.097
-
ATP
-
wild type enzyme with 2'-deoxyadenosine as phosphate acceptor, pH 7.6
0.11
-
ATP
-
cosubstrate deoxycytidine, 37C, pH 8.0
0.2
-
ATP
-
cosubstrate cytosine arabinoside, 37C, pH 8.0
0.00041
-
beta-D-arabinofuranosylcytosine
-
cosubstrate UTP 37C, pH 8.0
0.015
-
beta-D-arabinofuranosylcytosine
-
cosubstrate ATP 37C, pH 8.0
0.00065
-
cladribine
-
pH 7.6, 37C, wild-type enzyme, with co-substrate UTP
0.0016
-
cladribine
-
pH 7.6, 37C, enzyme mutant S74E, with co-substrate UTP
0.0024
-
cladribine
-
pH 7.6, 37C, wild-type enzyme, with co-substrate ATP
0.0155
-
cladribine
-
pH 7.6, 37C, enzyme mutant S74E, with co-substrate ATP
0.0087
-
clofarabine
-
pH 7.6, 37C, wild-type enzyme, with co-substrate UTP
0.0155
-
clofarabine
-
pH 7.6, 37C, enzyme mutant S74E, with co-substrate UTP
0.022
-
clofarabine
-
pH 7.6, 37C, wild-type enzyme, with co-substrate ATP
0.0325
-
clofarabine
-
pH 7.6, 37C, enzyme mutant S74E, with co-substrate ATP
0.0013
-
CTP
-
cosubstrate 2'-deoxycytidine, 37C, pH 7.4
0.45
-
cytidine
-
37C, pH 7.0
1.4
-
cytidine
-
37C, pH 8.0
0.002
-
cytosine arabinoside
-
L-isomer, 25C, pH 7.6
0.002
-
cytosine arabinoside
-
deoxycytidine, cytosolic isozyme I, pH 7.5, 37C
0.007
-
cytosine arabinoside
-
cytosolic isozyme I, pH 7.5, 37C
0.02
0.04
cytosine arabinoside
-
37C, pH 8.0
0.02
0.04
cytosine arabinoside
-
D-isomer; pH 7.6, 25C
0.02
0.04
cytosine arabinoside
-
pH 7.0, 37C
0.02
0.04
cytosine arabinoside
-
pH 8.0, 37C
0.02
0.04
cytosine arabinoside
-
D-isomer
0.0243
-
D-thymidine
-
mutant enzyme R104L/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
0.144
-
D-thymidine
-
mutant enzyme R104M/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
0.12
-
deoxyadenosine
-
pH 8.0, 37C
0.15
-
deoxyadenosine
-
pH 8.0
0.5
-
deoxyadenosine
-
37C, pH 7.0
0.89
-
deoxyadenosine
-
37C, pH 7.5
0.00007
-
Deoxycytidine
-
pH 7.6, 37C, wild-type enzyme, with co-substrate ATP
0.00009
-
Deoxycytidine
-
pH 7.6, 37C, wild-type enzyme, with co-substrate UTP
0.00013
-
Deoxycytidine
-
cosubstrate UTP 37C, pH 8.0
0.00018
-
Deoxycytidine
-
pH 7.6, 37C, enzyme mutant S74E, with co-substrate UTP
0.00027
-
Deoxycytidine
-
pH 7.6, 37C, enzyme mutant S74E, with co-substrate ATP
0.00057
-
Deoxycytidine
-
cosubstrate ATP 37C, pH 8.0
0.0008
0.0015
Deoxycytidine
-
37C, pH 7.0
0.0008
0.0015
Deoxycytidine
-
pH 8.0, 37C
0.001
-
Deoxycytidine
-
wild-type, pH 7.5, 30C; wild-type, pH 7.5, 37C
0.00104
-
Deoxycytidine
-
mutant R104Q/D133G, pH 7.5, 30C
0.00141
-
Deoxycytidine
-
mutant D47E/R104Q/D133G/N163I/F242L, pH 7.5, 30C
0.00154
-
Deoxycytidine
-
mutant A100V/R104M/D133A, pH 7.5, 37C
0.002
-
Deoxycytidine
-
mutant R104M/D133A, pH 7.5, 37C
0.0033
0.0093
Deoxycytidine
-
37C, pH 8.0
0.0033
0.0093
Deoxycytidine
-
-
0.00455
-
Deoxycytidine
-
mutant R104M/D133S, pH 7.5, 37C
0.00525
-
Deoxycytidine
-
mutant A100V/R104M/D133S, pH 7.5, 37C
0.0086
-
Deoxycytidine
-
mutant R104Q/D133N, pH 7.5, 30C
0.0118
-
Deoxycytidine
-
mutant R104M/D133N, pH 7.5, 37C
0.014
0.0167
Deoxycytidine
-
37C, pH 8.0
0.014
0.0167
Deoxycytidine
-
37C, pH 8.0; cytosine arabinoside-induced cells, 37C, pH 8.0
0.014
0.0167
Deoxycytidine
-
mitochondrial isozyme, pH 7.5, 37C; pH 7.5, 37C
0.014
-
Deoxycytidine
-
37C, pH 8.0
0.0209
-
Deoxycytidine
-
mutant R104M/D133T, pH 7.5, 37C
0.071
-
Deoxycytidine
-
mutant A100V/R104M/D133T, pH 7.5, 37C
0.15
-
deoxyguanosine
-
pH 8.0, 37C
0.33
0.43
deoxyguanosine
-
-
0.33
0.43
deoxyguanosine
-
37C, pH 7.0
0.64
-
deoxyguanosine
-
37C, pH 7.5
3
-
deoxyguanosine
-
37C, pH 8.0
0.001
-
dTTP
-
cosubstrate 2'-deoxycytidine, 37C, pH 7.4
0.028
-
fludarabine
-
pH 7.6, 37C, wild-type enzyme, with co-substrate UTP
0.142
-
fludarabine
-
pH 7.6, 37C, enzyme mutant S74E, with co-substrate UTP
0.45
-
fludarabine
-
pH 7.6, 37C, wild-type enzyme, with co-substrate ATP
0.551
-
fludarabine
-
pH 7.6, 37C, enzyme mutant S74E, with co-substrate ATP
0.0161
-
gemcitabine
-
wild type enzyme, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
0.0338
-
gemcitabine
-
mutant enzyme R104L/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
0.0562
-
gemcitabine
-
mutant enzyme R104M/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
0.0009
-
GTP
-
cosubstrate 2'-deoxycytidine, 37C, pH 7.4
0.0178
-
L-thymidine
-
mutant enzyme R104L/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
0.00388
-
thymidine
-
mutant A100V/R104M/D133T, pH 7.5, 37C
0.00558
-
thymidine
-
mutant A100V/R104M/D133S, pH 7.5, 37C
0.0058
-
thymidine
-
mutant R104M/D133T, pH 7.5, 37C
0.0189
-
thymidine
-
mutant R104M/D133S, pH 7.5, 37C
0.025
-
thymidine
-
mutant D47E/R104Q/D133G/N163I/F242L, pH 7.5, 30C
0.0256
-
thymidine
-
mutant R104M/D133N, pH 7.5, 37C
0.0257
-
thymidine
-
mutant R104Q/D133G, pH 7.5, 30C
0.031
-
thymidine
-
mutant A100V/R104M/D133A, pH 7.5, 37C
0.036
-
thymidine
-
mutant R104Q/D133N, pH 7.5, 30C
0.074
-
thymidine
-
mutant R104M/D133A, pH 7.5, 37C
3.485
-
thymidine
-
wild-type, pH 7.5, 30C; wild-type, pH 7.5, 37C
0.011
-
troxacitabine
-
wild type enzyme with UTP as phosphate donor, 37C, pH 7.5
0.013
-
troxacitabine
-
wild type enzyme with ATP as phosphate donor, 37C, pH 7.5
0.057
-
troxacitabine
-
C9S/C45S/C59S/C146S mutant enzyme with ATP as phosphate donor, 37C, pH 7.5
0.058
-
troxacitabine
-
C9S/C45S/C59S/C146Smutant enzyme with UTP as phosphate donor, 37C, pH 7.5
0.0005
-
UTP
-
cosubstrate 2'-deoxycytidine, 37C, pH 7.4
0.0015
-
UTP
-
residues 65-79 deletion mutant with 2'-deoxycytidine as cosubstrate
0.0023
-
UTP
-
wild type enzyme deletion mutant with 2'-deoxycytidine as cosubstrate
0.0047
-
UTP
-
residues 65-79 deletion mutant with 1-beta-D-arabinofuranosylcytosine as cosubstrate
0.008
-
UTP
-
cosubstrate (-)-beta-2',3'-dideoxy-3'-thiacytidine, wild-type, 37C, pH 7.5
0.01
-
UTP
-
wild type enzyme deletion mutant with 1-beta-D-arabinofuranosylcytosine as cosubstrate
0.0106
-
UTP
-
cosubstrate troxacitabine, wild-type, 37C, pH 7.5
0.011
-
UTP
-
wild type enzyme with 2'-deoxycytidine as phosphate acceptor, pH 7.6
0.0149
-
UTP
-
cosubstrate (-)-beta-2',3'-dideoxy-3'-thiacytidine, mutant C9S/C45S/C59S/C146S, 37C, pH 7.5
0.017
-
UTP
-
C185A mutant enzyme with 2'-deoxycytidine as phosphate acceptor, pH 7.6
0.02
-
UTP
-
C185A mutant enzyme with 2'-deoxyadenosine as phosphate acceptor, pH 7.6
0.04
-
UTP
-
wild type enzyme with 2'-deoxyadenosine as phosphate acceptor, pH 7.6
0.0578
-
UTP
-
cosubstrate troxacitabine, mutant C9S/C45S/C59S/C146S, 37C, pH 7.5
0.138
-
L-thymidine
-
mutant enzyme R104M/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
additional information
-
additional information
-
kinetic study
-
additional information
-
additional information
-
kinetic study; linear kinetics with deoxyguanosine or cytidine, bimodal kinetics with deoxycytidine as substrate
-
additional information
-
additional information
-
Km-values of a variety of substrate derivatives
-
additional information
-
additional information
-
linear kinetics with deoxyguanosine or cytidine, bimodal kinetics with deoxycytidine as substrate
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
kinetic study
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
kinetic study
-
additional information
-
additional information
-
Km-values of D-and L-cytidine analogues
-
additional information
-
additional information
-
Km-values of D-and L-analogues of cytidine and adenosine
-
additional information
-
additional information
-
no Michaelis-Menten kinetics, but negative cooperativity
-
additional information
-
additional information
-
steady-state fluorescent measurements, substrate binding constants, recombinant enzyme
-
additional information
-
additional information
-
kinetic properties of the enzyme are modulated in vivo by phosphorylation of Ser74, mechanism, overview
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.028
-
(-)-beta-2',3'-dideoxy-3'-thiacytidine
-
C9S/C45S/C59S/C146S mutant enzyme with ATP as phosphate donor, 37C, pH 7.5
0.03
-
(-)-beta-2',3'-dideoxy-3'-thiacytidine
-
wild type enzyme with ATP as phosphate donor, 37C, pH 7.5
0.072
-
(-)-beta-2',3'-dideoxy-3'-thiacytidine
-
C9S/C45S/C59S/C146S mutant enzyme with UTP as phosphate donor, 37C, pH 7.5
0.102
-
(-)-beta-2',3'-dideoxy-3'-thiacytidine
-
wild type enzyme with UTP as phosphate donor, 37C, pH 7.5
0.15
-
1-beta-D-arabinofuranosylcytosine
-
residues 65-79 deletion mutant with UTP as cosubstrate
0.17
-
1-beta-D-arabinofuranosylcytosine
-
wild type enzyme with UTP as cosubstrate
0.3
-
1-beta-D-arabinofuranosylcytosine
-
wild type enzyme with ATP as cosubstrate
0.3
-
1-beta-D-arabinofuranosylcytosine
-
mutant S74Q, pH 7.5, 25C
0.32
-
1-beta-D-arabinofuranosylcytosine
-
wild-type, pH 7.5, 25C
0.33
-
1-beta-D-arabinofuranosylcytosine
-
mutant S74A, pH 7.5, 25C
0.41
-
1-beta-D-arabinofuranosylcytosine
-
residues 65-79 deletion mutant with ATP as cosubstrate
0.57
-
1-beta-D-arabinofuranosylcytosine
-
mutant S74D, pH 7.5, 25C
1.06
-
1-beta-D-arabinofuranosylcytosine
-
mutant S74E, pH 7.5, 25C
0.34
-
1-beta-D-arabinosylcytosine
-
wild type enzyme, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
0.79
-
1-beta-D-arabinosylcytosine
-
mutant enzyme R104L/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
1.43
-
1-beta-D-arabinosylcytosine
-
mutant enzyme R104M/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
0.44
-
2',2'-difluorodeoxycytidine
-
wild-type, pH 7.5, 25C
0.45
-
2',2'-difluorodeoxycytidine
-
mutant S74Q, pH 7.5, 25C
0.5
-
2',2'-difluorodeoxycytidine
-
mutant S74A, pH 7.5, 25C
0.9
-
2',2'-difluorodeoxycytidine
-
mutant S74D, pH 7.5, 25C
1.21
-
2',2'-difluorodeoxycytidine
-
mutant S74E, pH 7.5, 25C
0.31
-
2'-deoxyadenosine
-
residues 65-79 deletion mutant with UTP as cosubstrate
0.33
-
2'-deoxyadenosine
-
wild type enzyme with UTP as cosubstrate
0.37
-
2'-deoxyadenosine
-
cosubstrate UTP, pH 7.5, 37C
0.69
-
2'-deoxyadenosine
-
mutant S74E, pH 7.5, 25C
0.77
-
2'-deoxyadenosine
-
wild-type, pH 7.5, 25C
0.9
-
2'-deoxyadenosine
-
mutant S74Q, pH 7.5, 25C
1
-
2'-deoxyadenosine
-
mutant S74D, pH 7.5, 25C
1.08
-
2'-deoxyadenosine
-
mutant D47E/R104Q/D133G/N163I/F242L, pH 7.5, 30C
1.12
-
2'-deoxyadenosine
-
mutant S74A, pH 7.5, 25C
1.7
-
2'-deoxyadenosine
-
wild type enzyme with ATP as cosubstrate
1.75
-
2'-deoxyadenosine
-
mutant R104Q/D133G, pH 7.5, 30C
2
-
2'-deoxyadenosine
-
mutant R104Q/D133N, pH 7.5, 30C
2.1
-
2'-deoxyadenosine
-
cosubstrate ATP, pH 7.5, 37C
2.13
-
2'-deoxyadenosine
-
wild type enzyme, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
2.67
-
2'-deoxyadenosine
-
mutant A100V/R104M/D133T, pH 7.5, 37C
2.71
-
2'-deoxyadenosine
-
mutant R104M/D133A, pH 7.5, 37C
2.8
-
2'-deoxyadenosine
-
residues 65-79 deletion mutant with ATP as cosubstrate
3.1
-
2'-deoxyadenosine
-
wild-type, pH 7.5, 30C; wild-type, pH 7.5, 37C
3.37
-
2'-deoxyadenosine
-
mutant A100V/R104M/D133S, pH 7.5, 37C
3.4
-
2'-deoxyadenosine
-
mutant A100V/R104M/D133A, pH 7.5, 37C
3.47
-
2'-deoxyadenosine
-
mutant R104M/D133N, pH 7.5, 37C
4.14
-
2'-deoxyadenosine
-
mutant R104M/D133T, pH 7.5, 37C
4.51
-
2'-deoxyadenosine
-
mutant enzyme R104M/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
4.85
-
2'-deoxyadenosine
-
mutant R104M/D133S, pH 7.5, 37C
5.72
-
2'-deoxyadenosine
-
mutant enzyme R104L/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
0.033
-
2'-deoxycytidine
-
less than 0.001 mM, wild type enzyme with ATP as cosubstrate
0.04
-
2'-deoxycytidine
-
mutant S74A, pH 7.5, 25C; mutant S74Q, pH 7.5, 25C; wild-type, pH 7.5, 25C
0.04
-
2'-deoxycytidine
-
wild type enzyme, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
0.044
-
2'-deoxycytidine
-
less than 0.001 mM, wild type enzyme with UTP as cosubstrate
0.049
-
2'-deoxycytidine
-
residues 65-79 deletion mutant with ATP as cosubstrate
0.088
-
2'-deoxycytidine
-
less than 0.001 mM, residues 65-79 deletion mutant with UTP as cosubstrate
0.11
-
2'-deoxycytidine
-
pH 7.6, 37C, recombinant enzyme
0.16
-
2'-deoxycytidine
-
mutant S74D, pH 7.5, 25C
0.25
-
2'-deoxycytidine
-
mutant enzyme R104L/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
0.45
-
2'-deoxycytidine
-
mutant S74E, pH 7.5, 25C
1.8
-
2'-deoxycytidine
-
mutant enzyme R104M/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
0.31
-
2'-deoxyguanosine
-
mutant A100V/R104M/D133A, pH 7.5, 37C
0.32
-
2'-deoxyguanosine
-
residues 65-79 deletion mutant with UTP as cosubstrate
0.33
-
2'-deoxyguanosine
-
wild type enzyme with UTP as cosubstrate
0.36
-
2'-deoxyguanosine
-
mutant S74E, pH 7.5, 25C
0.53
-
2'-deoxyguanosine
-
cosubstrate UTP, pH 7.5, 37C
0.57
-
2'-deoxyguanosine
-
mutant S74D, pH 7.5, 25C
0.65
-
2'-deoxyguanosine
-
mutant S74Q, pH 7.5, 25C
0.68
-
2'-deoxyguanosine
-
mutant S74A, pH 7.5, 25C
0.73
-
2'-deoxyguanosine
-
wild-type, pH 7.5, 25C
1.18
-
2'-deoxyguanosine
-
mutant D47E/R104Q/D133G/N163I/F242L, pH 7.5, 30C
1.23
-
2'-deoxyguanosine
-
mutant R104M/D133A, pH 7.5, 37C
1.5
-
2'-deoxyguanosine
-
mutant R104Q/D133G, pH 7.5, 30C
1.72
-
2'-deoxyguanosine
-
mutant A100V/R104M/D133S, pH 7.5, 37C
1.73
-
2'-deoxyguanosine
-
mutant enzyme R104M/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
1.92
-
2'-deoxyguanosine
-
mutant R104Q/D133N, pH 7.5, 30C
2.2
-
2'-deoxyguanosine
-
residues 65-79 deletion mutant with ATP as cosubstrate
2.29
-
2'-deoxyguanosine
-
mutant A100V/R104M/D133T, pH 7.5, 37C
2.5
-
2'-deoxyguanosine
-
mutant R104M/D133T, pH 7.5, 37C
2.5
-
2'-deoxyguanosine
-
cosubstrate ATP, pH 7.5, 37C
2.6
-
2'-deoxyguanosine
-
wild type enzyme with ATP as cosubstrate
2.6
-
2'-deoxyguanosine
-
wild type enzyme, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
3.26
-
2'-deoxyguanosine
-
wild-type, pH 7.5, 30C; wild-type, pH 7.5, 37C
3.59
-
2'-deoxyguanosine
-
mutant R104M/D133N, pH 7.5, 37C
3.66
-
2'-deoxyguanosine
-
mutant enzyme R104L/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
4.38
-
2'-deoxyguanosine
-
mutant R104M/D133S, pH 7.5, 37C
0.02
-
2,5-difluoro-4-[1-(2-deoxy-beta-L-ribofuranosyl)]-aniline
-
pH 7.6, 37C, recombinant enzyme
0.37
-
2-chlorodeoxyadenosine
-
cosubstrate UTP, pH 7.5, 37C
0.6
-
2-chlorodeoxyadenosine
-
cosubstrate ATP, pH 7.5, 37C
0.012
-
ATP
-
cosubstrate L-2'-deoxycytidine, wild-type, 37C, pH 7.5
0.028
-
ATP
-
wild type enzyme with 2'-deoxycytidine as cosubstrate
0.028
-
ATP
-
cosubstrate (-)-beta-2',3'-dideoxy-3'-thiacytidine, mutant C9S/C45S/C59S/C146S, 37C, pH 7.5
0.03
-
ATP
-
cosubstrate (-)-beta-2',3'-dideoxy-3'-thiacytidine, wild-type, 37C, pH 7.5
0.033
-
ATP
-
cosubstrate D-2'-deoxycytidine, wild-type, 37C, pH 7.5
0.036
-
ATP
-
cosubstrate L-2'-deoxycytidine, mutant C9S/C45S/C59S/C146S, 37C, pH 7.5
0.039
-
ATP
-
residues 65-79 deletion mutant with 2'-deoxycytidine as cosubstrate
0.095
-
ATP
-
cosubstrate troxacitabine, wild-type, 37C, pH 7.5
0.173
-
ATP
-
cosubstrate D-2'-deoxycytidine, mutant C9S/C45S/C59S/C146S, 37C, pH 7.5
0.192
-
ATP
-
cosubstrate troxacitabine, mutant C9S/C45S/C59S/C146S, 37C, pH 7.5
0.36
-
ATP
-
residues 65-79 deletion mutant with 1-beta-D-arabinofuranosylcytosine as cosubstrate
0.4
-
ATP
-
wild type enzyme with 1-beta-D-arabinofuranosylcytosine as cosubstrate
0.0804
-
cladribine
-
pH 7.6, 37C, wild-type enzyme, with co-substrate UTP
0.172
-
cladribine
-
pH 7.6, 37C, wild-type enzyme, with co-substrate ATP
0.211
-
cladribine
-
pH 7.6, 37C, enzyme mutant S74E, with co-substrate UTP
1.386
-
cladribine
-
pH 7.6, 37C, enzyme mutant S74E, with co-substrate ATP
0.486
-
clofarabine
-
pH 7.6, 37C, wild-type enzyme, with co-substrate UTP
0.88
-
clofarabine
-
pH 7.6, 37C, enzyme mutant S74E, with co-substrate UTP
1.11
-
clofarabine
-
pH 7.6, 37C, wild-type enzyme, with co-substrate ATP
2.45
-
clofarabine
-
pH 7.6, 37C, enzyme mutant S74E, with co-substrate ATP
1.74
-
D-thymidine
-
mutant enzyme R104M/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
3.2
-
D-thymidine
-
mutant enzyme R104L/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
0.015
-
Deoxycytidine
-
pH 7.6, 37C, wild-type enzyme, with co-substrate ATP
0.021
-
Deoxycytidine
-
pH 7.6, 37C, wild-type enzyme, with co-substrate UTP
0.064
-
Deoxycytidine
-
wild-type, pH 7.5, 30C; wild-type, pH 7.5, 37C
0.123
-
Deoxycytidine
-
pH 7.6, 37C, enzyme mutant S74E, with co-substrate UTP
0.183
-
Deoxycytidine
-
pH 7.6, 37C, enzyme mutant S74E, with co-substrate ATP
0.21
-
Deoxycytidine
-
mutant D47E/R104Q/D133G/N163I/F242L, pH 7.5, 30C
0.37
-
Deoxycytidine
-
mutant R104Q/D133G, pH 7.5, 30C
0.58
-
Deoxycytidine
-
mutant R104M/D133A, pH 7.5, 37C
1.2
-
Deoxycytidine
-
mutant A100V/R104M/D133A, pH 7.5, 37C
1.3
-
Deoxycytidine
-
mutant R104Q/D133N, pH 7.5, 30C
1.7
-
Deoxycytidine
-
mutant R104M/D133S, pH 7.5, 37C
2.1
-
Deoxycytidine
-
mutant A100V/R104M/D133S, pH 7.5, 37C
2.23
-
Deoxycytidine
-
mutant R104M/D133N, pH 7.5, 37C
2.86
-
Deoxycytidine
-
mutant R104M/D133T, pH 7.5, 37C
3.54
-
Deoxycytidine
-
mutant A100V/R104M/D133T, pH 7.5, 37C
1330
-
Deoxycytidine
-
cytosine arabinoside-induced cells
78300
-
Deoxycytidine
-
-
0.177
-
fludarabine
-
pH 7.6, 37C, wild-type enzyme, with co-substrate UTP
0.363
-
fludarabine
-
pH 7.6, 37C, enzyme mutant S74E, with co-substrate UTP
1.005
-
fludarabine
-
pH 7.6, 37C, enzyme mutant S74E, with co-substrate ATP
1.334
-
fludarabine
-
pH 7.6, 37C, wild-type enzyme, with co-substrate ATP
0.39
-
gemcitabine
-
wild type enzyme, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
2.01
-
gemcitabine
-
mutant enzyme R104L/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
2.68
-
gemcitabine
-
mutant enzyme R104M/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
1.33
-
L-thymidine
-
mutant enzyme R104L/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
3.13
-
L-thymidine
-
mutant enzyme R104M/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
0.38
-
thymidine
-
wild-type, pH 7.5, 30C; wild-type, pH 7.5, 37C
0.68
-
thymidine
-
mutant D47E/R104Q/D133G/N163I/F242L, pH 7.5, 30C
1.01
-
thymidine
-
mutant R104Q/D133G, pH 7.5, 30C
1.49
-
thymidine
-
mutant R104M/D133T, pH 7.5, 37C
1.51
-
thymidine
-
mutant R104Q/D133N, pH 7.5, 30C
1.57
-
thymidine
-
mutant A100V/R104M/D133T, pH 7.5, 37C
1.88
-
thymidine
-
mutant R104M/D133A, pH 7.5, 37C
1.91
-
thymidine
-
mutant A100V/R104M/D133S, pH 7.5, 37C
2.27
-
thymidine
-
mutant R104M/D133N, pH 7.5, 37C
2.33
-
thymidine
-
mutant R104M/D133S, pH 7.5, 37C
3.29
-
thymidine
-
mutant A100V/R104M/D133A, pH 7.5, 37C
0.095
-
troxacitabine
-
wild type enzyme with ATP as phosphate donor, 37C, pH 7.5
0.192
-
troxacitabine
-
C9S/C45S/C59S/C146S mutant enzyme with ATP as phosphate donor, 37C, pH 7.5
6.08
-
troxacitabine
-
C9S/C45S/C59S/C146S mutant enzyme with UTP as phosphate donor, 37C, pH 7.5
0.01
-
UTP
-
cosubstrate L-2'-deoxycytidine, wild-type, 37C, pH 7.5
0.031
-
UTP
-
wild type enzyme deletion mutant with 2'-deoxycytidine as cosubstrate
0.041
-
UTP
-
residues 65-79 deletion mutant with 2'-deoxycytidine as cosubstrate
0.042
-
UTP
-
cosubstrate L-2'-deoxycytidine, mutant C9S/C45S/C59S/C146S, 37C, pH 7.5
0.049
-
UTP
-
cosubstrate D-2'-deoxycytidine, wild-type, 37C, pH 7.5
0.072
-
UTP
-
cosubstrate (-)-beta-2',3'-dideoxy-3'-thiacytidine, mutant C9S/C45S/C59S/C146S, 37C, pH 7.5
0.075
-
UTP
-
residues 65-79 deletion mutant with 1-beta-D-arabinofuranosylcytosine as cosubstrate
0.093
-
UTP
-
wild type enzyme deletion mutant with 1-beta-D-arabinofuranosylcytosine as cosubstrate
0.102
-
UTP
-
cosubstrate (-)-beta-2',3'-dideoxy-3'-thiacytidine, wild-type, 37C, pH 7.5
0.179
-
UTP
-
cosubstrate troxacitabine, wild-type, 37C, pH 7.5
0.217
-
UTP
-
cosubstrate D-2'-deoxycytidine, mutant C9S/C45S/C59S/C146S, 37C, pH 7.5
0.524
-
UTP
-
cosubstrate troxacitabine, mutant C9S/C45S/C59S/C146S, 37C, pH 7.5
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
10.5
-
1-beta-D-arabinosylcytosine
-
mutant enzyme R104M/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
8478
15.6
-
1-beta-D-arabinosylcytosine
-
mutant enzyme R104L/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
8478
26
-
1-beta-D-arabinosylcytosine
-
wild type enzyme, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
8478
4.3
-
2'-deoxyadenosine
-
mutant enzyme R104M/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
357
18.6
-
2'-deoxyadenosine
-
wild type enzyme, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
357
35.2
-
2'-deoxyadenosine
-
mutant enzyme R104L/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
357
13.3
-
2'-deoxycytidine
-
kcat/Km above 13.3/sec*mM, wild type enzyme, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
486
31.3
-
2'-deoxycytidine
-
mutant enzyme R104L/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
486
315.8
-
2'-deoxycytidine
-
mutant enzyme R104M/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
486
0.9
-
2'-deoxyguanosine
-
mutant enzyme R104M/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
504
1.6
-
2'-deoxyguanosine
-
mutant enzyme R104L/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
504
11.3
-
2'-deoxyguanosine
-
wild type enzyme, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
504
74.3
-
cladribine
-
pH 7.6, 37C, wild-type enzyme, with co-substrate ATP
5796
90.2
-
cladribine
-
pH 7.6, 37C, enzyme mutant S74E, with co-substrate ATP
5796
130
-
cladribine
-
pH 7.6, 37C, wild-type enzyme, with co-substrate UTP
5796
136
-
cladribine
-
pH 7.6, 37C, enzyme mutant S74E, with co-substrate UTP
5796
50.1
-
clofarabine
-
pH 7.6, 37C, wild-type enzyme, with co-substrate ATP
5855
56.3
-
clofarabine
-
pH 7.6, 37C, wild-type enzyme, with co-substrate UTP
5855
57.6
-
clofarabine
-
pH 7.6, 37C, enzyme mutant S74E, with co-substrate UTP
5855
76.8
-
clofarabine
-
pH 7.6, 37C, enzyme mutant S74E, with co-substrate ATP
5855
12.1
-
D-thymidine
-
mutant enzyme R104M/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
14935
131.7
-
D-thymidine
-
mutant enzyme R104L/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
14935
236
-
Deoxycytidine
-
pH 7.6, 37C, wild-type enzyme, with co-substrate ATP
451
257
-
Deoxycytidine
-
pH 7.6, 37C, wild-type enzyme, with co-substrate UTP
451
676
-
Deoxycytidine
-
pH 7.6, 37C, enzyme mutant S74E, with co-substrate ATP
451
745
-
Deoxycytidine
-
pH 7.6, 37C, enzyme mutant S74E, with co-substrate UTP
451
1.8
-
fludarabine
-
pH 7.6, 37C, enzyme mutant S74E, with co-substrate ATP
4150
2.6
-
fludarabine
-
pH 7.6, 37C, enzyme mutant S74E, with co-substrate UTP
4150
3
-
fludarabine
-
pH 7.6, 37C, wild-type enzyme, with co-substrate ATP
4150
6.4
-
fludarabine
-
pH 7.6, 37C, wild-type enzyme, with co-substrate UTP
4150
24.2
-
gemcitabine
-
wild type enzyme, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
1899
47.7
-
gemcitabine
-
mutant enzyme R104M/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
1899
59.5
-
gemcitabine
-
mutant enzyme R104L/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
1899
22.7
-
L-thymidine
-
mutant enzyme R104M/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
14107
74.7
-
L-thymidine
-
mutant enzyme R104L/D133A, in 100 mM Tris, pH 7.5, 100 mM KCl, 10 mM MgCl2 and 1 mM ATP, at 37C
14107
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.3
-
2'-O-methylcytidine
-
37C, pH 7.6
0.02
-
3'-O-methyl-2'deoxycytidine
-
37C, pH 7.6
0.032
-
5'-O-ethyl-2'-deoxycytidine
-
37C, pH 7.6
0.23
-
5'-O-methyl-2'-deoxycytidine
-
37C, pH 7.6
0.0015
-
dCMP
-
cosubstrate UTP, 37C, pH 7.4
0.022
-
dCMP
-
cosubstrate deoxycytidine, 37C, pH 7.4
0.0015
-
dCTP
-
pH 7.6, 37C, enzyme mutant S74E, with substrates cladribine and ATP, mixed inhibition
0.0029
-
dCTP
-
pH 7.6, 37C, enzyme mutant S74E, with substrates deoxycytidine and ATP, mixed inhibition
0.0058
-
dCTP
-
pH 7.6, 37C, wild-type enzyme, with substrates cladribine and ATP, mixed inhibition
0.027
-
dCTP
-
pH 7.6, 37C, enzyme mutant S74E, with substrates cladribine and UTP, uncompetitive inhibition
0.03
-
dCTP
-
pH 7.6, 37C, wild-type enzyme, with substrates deoxycytidine and ATP, mixed inhibition
0.05
-
dCTP
-
pH 7.6, 37C, wild-type enzyme, with substrates cladribine and UTP, uncompetitive inhibition
0.052
-
dCTP
-
pH 7.6, 37C, enzyme mutant S74E, with substrates deoxycytidine and UTP, uncompetitive inhibition
0.0004
-
UDP
-
cosubstrate UTP, 37C, pH 7.4
0.0069
-
UDP
-
cosubstrate deoxycytidine, 37C, pH 7.4
0.398
-
dCTP
-
pH 7.6, 37C, wild-type enzyme, with substrates deoxycytidine and UTP, uncompetitive inhibition
additional information
-
additional information
-
steady-state fluorescent measurement, inhibitor binding constant, recombinant enzyme
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00012
-
2'-deoxy-5-fluorocytidine
-
-
0.000003
-
2-(2-[1-[6-(1-benzothiophen-2-yl)pyrimidin-4-yl]piperidin-4-yl]ethoxy)-5-fluoropyrimidin-4-amine
-
-
0.000034
-
2-([1-[6-(1-benzothiophen-2-yl)pyrimidin-4-yl]piperidin-4-yl]methoxy)-5-fluoropyrimidin-4-amine
-
-
0.000038
-
2-([1-[6-(1-benzothiophen-2-yl)pyrimidin-4-yl]piperidin-4-yl]oxy)-5-fluoropyrimidin-4-amine
-
-
0.000003
-
2-([1-[6-(2-chlorophenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy)-5-fluoropyrimidin-4-amine
-
-
0.00001
-
2-([1-[6-(2-ethylphenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy)-5-fluoropyrimidin-4-amine
-
-
0.000022
-
2-([1-[6-(3-chlorophenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy)-5-fluoropyrimidin-4-amine
-
-
0.000009
-
2-([1-[6-(4-chloro-2-methylphenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy)-5-fluoropyrimidin-4-amine
-
-
0.000019
-
2-([1-[6-(4-chlorophenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy)-5-fluoropyrimidin-4-amine
-
-
0.000003
-
2-([1-[6-(biphenyl-2-yloxy)pyrimidin-4-yl]piperidin-4-yl]oxy)-5-fluoropyrimidin-4-amine
-
-
0.000063
-
2-([6-[4-(4-amino-2-oxopyrimidin-1(2H)-yl)piperidin-1-yl]-5-fluoropyrimidin-4-yl]oxy)benzonitrile
-
-
0.000005
-
2-[(6-[4-[(4-amino-5-fluoropyrimidin-2-yl)oxy]piperidin-1-yl]-2-bromopyrimidin-4-yl)oxy]benzonitrile
-
-
0.00001
-
2-[(6-[4-[(4-amino-5-fluoropyrimidin-2-yl)oxy]piperidin-1-yl]-2-methylpyrimidin-4-yl)oxy]benzonitrile
-
-
0.000002
-
2-[(6-[4-[(4-amino-5-fluoropyrimidin-2-yl)oxy]piperidin-1-yl]-5-fluoropyrimidin-4-yl)oxy]-5-methoxybenzonitrile
-
-
0.000001
-
2-[(6-[4-[(4-amino-5-fluoropyrimidin-2-yl)oxy]piperidin-1-yl]-5-fluoropyrimidin-4-yl)oxy]benzonitrile
-
-
0.000021
-
2-[(6-[4-[(4-amino-5-fluoropyrimidin-2-yl)oxy]piperidin-1-yl]-5-methylpyrimidin-4-yl)oxy]benzonitrile
-
-
0.000003
-
2-[(6-[4-[(4-amino-5-fluoropyrimidin-2-yl)oxy]piperidin-1-yl]pyrimidin-4-yl)oxy]-5-methoxybenzonitrile
-
-
0.000003
-
2-[(6-[4-[(4-amino-5-fluoropyrimidin-2-yl)oxy]piperidin-1-yl]pyrimidin-4-yl)oxy]benzonitrile
-
-
0.0000007
-
2-[(6-[4-[(4-aminopyrimidin-2-yl)oxy]piperidin-1-yl]-5-fluoropyrimidin-4-yl)oxy]benzonitrile
-
-
0.00072
-
2-[[6-(1-benzothiophen-2-yl)pyrimidin-4-yl]oxy]-5-fluoropyrimidin-4-amine
-
-
0.000089
-
3'-[[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]sulfamoyl]biphenyl-4-carboxamide
-
-
0.000001
-
3-[(6-[4-[(4-amino-5-fluoropyrimidin-2-yl)oxy]piperidin-1-yl]-2-fluoropyrimidin-4-yl)oxy]-4-methoxybenzonitrile
-
-
0.000005
-
3-[(6-[4-[(4-amino-5-fluoropyrimidin-2-yl)oxy]piperidin-1-yl]-5-fluoropyrimidin-4-yl)oxy]-4-methoxybenzonitrile
-
-
0.000004
-
3-[(6-[4-[(4-amino-5-fluoropyrimidin-2-yl)oxy]piperidin-1-yl]-5-fluoropyrimidin-4-yl)oxy]benzonitrile
-
-
0.000013
-
3-[(6-[4-[(4-amino-5-fluoropyrimidin-2-yl)oxy]piperidin-1-yl]pyrimidin-4-yl)oxy]benzonitrile
-
-
0.000024
-
4'-thio-beta-D-arabinofuranosylcytosine
-
IC50 0.000024 mM
0.00051
-
4-(1-benzothiophen-2-yl)-6-[4-(2-oxo-2-pyrrolidin-1-ylethyl)piperazin-1-yl]pyrimidine
-
-
0.00051
-
4-(1-benzothiophen-2-yl)-6-[4-(2-oxo-2-pyrrolidin-1-ylethyl)piperazin-1-yl]pyrimidine
-
-
0.051
-
5-chloro-4'-thio-beta-D-arabinofuranosylcytosine
-
IC50 0.051 mM
0.00012
-
5-Fluoro-2'-deoxycytidine
-
-
0.000004
-
5-fluoro-2-([1-[5-fluoro-6-(4-methoxyphenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy)pyrimidin-4-amine
-
-
0.000006
-
5-fluoro-2-([1-[6-(2-fluorophenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy)pyrimidin-4-amine
-
-
0.000005
-
5-fluoro-2-([1-[6-(2-methoxyphenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy)pyrimidin-4-amine
-
-
0.000009
-
5-fluoro-2-([1-[6-(2-methylphenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy)pyrimidin-4-amine
-
-
0.000023
-
5-fluoro-2-([1-[6-(3-methoxyphenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy)pyrimidin-4-amine
-
-
0.000033
-
5-fluoro-2-([1-[6-(4-methoxyphenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy)pyrimidin-4-amine
-
-
0.000021
-
5-fluoro-2-([1-[6-(4-methylphenoxy)pyrimidin-4-yl]piperidin-4-yl]oxy)pyrimidin-4-amine
-
-
0.000095
-
5-fluoro-2-[[1-(6-phenoxypyrimidin-4-yl)piperidin-4-yl]oxy]pyrimidin-4-amine
-
-
0.000002
-
5-fluoro-4'-thio-beta-D-arabinofuranosylcytosine
-
IC50 0.0000020 mM
0.0000055
-
cytosine arabinoside
-
IC50 0.0000055 mM
0.0138
-
LP-375752
-
in 50 mM Tris (pH 7.6)
0.00091
-
LP-503392
-
in 50 mM Tris (pH 7.6)
0.000021
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-2',4'-dichlorobiphenyl-3-sulfonamide
-
-
0.000045
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-2'-chlorobiphenyl-3-sulfonamide
-
-
0.000023
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-3'-chlorobiphenyl-3-carboxamide
-
-
0.000079
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-3'-chlorobiphenyl-3-sulfonamide
-
-
0.00035
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-3-bromobenzenesulfonamide
-
-
0.0019
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-3-bromobenzenesulfonamide
-
-
0.000021
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4''-chloro-2''-methyl-1,1':4',1''-terphenyl-3-carboxamide
-
-
0.000021
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4''-chloro-2''-methyl-1,1':4',1''-terphenyl-3-sulfonamide
-
-
0.000063
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-(methylsulfonyl)biphenyl-3-sulfonamide
-
-
0.000051
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-chlorobiphenyl-3-sulfonamide
-
-
0.000049
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-cyanobiphenyl-3-sulfonamide
-
-
0.0153
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-formylbiphenyl-3-sulfonamide
-
-
0.00003
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-methoxybiphenyl-3-carboxamide
-
-
0.000042
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-methoxybiphenyl-3-carboxamide
-
-
0.000064
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-methoxybiphenyl-3-sulfonamide
-
-
0.00011
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4'-methylbiphenyl-3-sulfonamide
-
-
0.0000017
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4-(1-benzothiophen-2-yl)pyridine-2-carboxamide
-
-
0.0027
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4-bromobenzenesulfonamide
-
-
0.0032
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]-4-nitrobenzenesulfonamide
-
-
0.0036
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]benzenesulfonamide
-
-
0.00026
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]biphenyl-3-carboxamide
-
-
0.00012
-
N-[(1S,3S)-3-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)cyclopentyl]biphenyl-3-sulfonamide
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.0000057
-
-
differentiated adipocytes
0.0000521
-
-
CEM lymphocytes
0.00088
-
-
cytosine arabinoside-induced cells
0.0048
-
-
37C, pH 7.0
0.00523
-
-
37C, pH 8.0
0.00632
-
-
37C, pH 8.0
0.012
-
-
37C, pH 8.0
0.0206
-
-
37C, pH 8.0
0.048
-
-
mitochondrial isozyme, pH 7.5, 37C
0.072
-
-
cytoplasmic isozyme I, pH 7.5, 37C
0.0846
-
-
37C, pH 8.0
0.11
0.15
-
pH 8.0, 37C
0.2
-
-
-
4
-
-
cytidine as substrate, 37C, pH 7.0
6.5
-
-
substrate dideoxythymidine, wild-type, pH 7.5, 37C
7.2
-
-
deoxyguanosine as substrate, 37C, pH 7.0
8
-
-
37C, pH 7.0
13.5
-
-
deoxyadenosine as substrate, 37C, pH 7.0
26
-
-
substrate 2'-deoxy-3'-thiacytidine, mutant A100V/R104M/D133T, pH 7.5, 37C
28
-
-
substrate dideoxythymidine, mutant R104M/D133S, pH 7.5, 37C
64
-
-
substrate dideoxythymidine, mutant A100V/R104M/D133A, pH 7.5, 37C
88
-
-
substrate 2'-deoxy-3'-thiacytidine, wild-type, pH 7.5, 37C
108
-
-
substrate dideoxythymidine, mutant R104M/D133T, pH 7.5, 37C
114
-
-
substrate 2'-deoxy-3'-thiacytidine, mutant R104M/D133T, pH 7.5, 37C
135
-
-
substrate dideoxythymidine, mutant A100V/R104M/D133T, pH 7.5, 37C
149
-
-
substrate 2'-deoxy-3'-thiacytidine, mutant A100V/R104M/D133A, pH 7.5, 37C
186
-
-
substrate dideoxythymidine, mutant A100V/R104M/D133S, pH 7.5, 37C
206
-
-
substrate dideoxythymidine, mutant D47E/R104Q/D133G/N163I/F242L, pH 7.5, 37C
270
-
-
substrate 2'-deoxy-3'-thiacytidine, mutant A100V/R104M/D133S, pH 7.5, 37C
545
-
-
substrate 2'-deoxy-3'-thiacytidine, mutant R104M/D133S, pH 7.5, 37C
599
-
-
substrate 1-beta-D-arabinosylcytosine, mutant A100V/R104M/D133T, pH 7.5, 37C
815
-
-
substrate 2'-deoxy-3'-thiacytidine, mutant D47E/R104Q/D133G/N163I/F242L, pH 7.5, 37C
984
-
-
substrate 1-beta-D-arabinosylcytosine, wild-type, pH 7.5, 37C
1387
-
-
substrate 1-beta-D-arabinosylcytosine, mutant R104M/D133T, pH 7.5, 37C
1648
-
-
substrate gemcitabine, wild-type, pH 7.5, 37C
2262
-
-
substrate gemcitabine, mutant A100V/R104M/D133T, pH 7.5, 37C
3177
-
-
substrate 1-beta-D-arabinosylcytosine, mutant A100V/R104M/D133S, pH 7.5, 37C
3308
-
-
substrate 1-beta-D-arabinosylcytosine, mutant A100V/R104M/D133A, pH 7.5, 37C
3339
-
-
substrate 1-beta-D-arabinosylcytosine, mutant R104M/D133SA, pH 7.5, 37C
4267
-
-
substrate gemcitabine, mutant R104M/D133T, pH 7.5, 37C
4400
-
-
substrate 1-beta-D-arabinosylcytosine, mutant D47E/R104Q/D133G/N163I/F242L, pH 7.5, 37C
4530
-
-
substrate gemcitabine, mutant A100V/R104M/D133A, pH 7.5, 37C
5624
-
-
substrate gemcitabine, mutant R104M/D133SA, pH 7.5, 37C
6009
-
-
substrate gemcitabine, mutant A100V/R104M/D133S, pH 7.5, 37C
6460
-
-
substrate gemcitabine, mutant D47E/R104Q/D133G/N163I/F242L, pH 7.5, 37C
additional information
-
-
-
additional information
-
-
substrate specificity
additional information
-
-
MTT assay method
additional information
-
-
catalytic efficiencies of the purified recombinant enzyme
additional information
-
-
relative enzyme activity in different cancer cell lines, overview
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5
7
-
broad
5.5
8.5
-
plateau, higher activity in Tris than in phosphate buffer
6
10
-
broad plateau, with very slight optima at pH 6 and 10
6
10
-
nearly flat response to pH-variations
7
-
-
broad
7.4
-
-
assay at
7.5
-
-
assay at
7.6
-
-
assay at
7.6
-
-
assay at
7.6
-
-
assay at
8
-
-
-
8
-
-
aassay at
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5
10
-
maximal activity at pH 5 and about half-maximal activity at pH 10
5.8
10
-
about half-maximal activity at pH 5.8 and pH 10, about 90% of maximal activity at pH 6.5 and pH 9
7
10
-
about 80% of maximal activity at pH 7 and about 65% of maximal activity at pH 10
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
-
-
assay at
25
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
50
-
-
-
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
27
37
-
moderately sensitive to variations of incubation temperature
37
55
-
about half-maximal activity at 37C and 55C
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
mononuclear cells used for experiments
Manually annotated by BRENDA team
-
low enzyme expression level
Manually annotated by BRENDA team
-
lowest specific activity among the cell lines used
Manually annotated by BRENDA team
-
P815-neoplasm cell line
Manually annotated by BRENDA team
-
enzyme activity increases up to 3fold when cells start to proliferate
Manually annotated by BRENDA team
-
proliferating lymphocyte
Manually annotated by BRENDA team
-
highest specific activity among the cell lines used
Manually annotated by BRENDA team
-
; low enzyme activity
Manually annotated by BRENDA team
-
enzyme activity increases up to 3fold when cells start to proliferate
Manually annotated by BRENDA team
-
very low enzyme expression
Manually annotated by BRENDA team
-
from acute myeloid leukemia (AML) patients; from peripheral blood; ML-1 cells
Manually annotated by BRENDA team
-
from spleen; leukemic T-lymphoblasts
Manually annotated by BRENDA team
-
leukemic T-lymphoblasts
Manually annotated by BRENDA team
-
cell line MOLT-4; leukemic T-lymphoblasts
Manually annotated by BRENDA team
-
from acute myeloid leukemia (AML) patients
Manually annotated by BRENDA team
-
various spontaneous leukemic cells
Manually annotated by BRENDA team
-
cell line MOLT-4
Manually annotated by BRENDA team
-
lymphomic
Manually annotated by BRENDA team
-
very low enzyme expression
Manually annotated by BRENDA team
-
high enzyme content in fetal liver, very low content in adult liver
Manually annotated by BRENDA team
-
adult non-small cell lung cancer
Manually annotated by BRENDA team
-
normal and leukemic
Manually annotated by BRENDA team
-
T-lymphoblasts, cell lines MOLT 4F, CCRF, CEM and RPMI 8402, B-lymphoblasts cell lines BALL 1 and EBV (Epstein-Barr-virus) transformed B-lymphoblasts
Manually annotated by BRENDA team
-
from human leukemia patients
Manually annotated by BRENDA team
-
normal, acute myeloid leukemic and HL60 promyelocytic cells
Manually annotated by BRENDA team
-
normal cells and various leukemic cell lines
Manually annotated by BRENDA team
-
tonsillar lymphocyte
Manually annotated by BRENDA team
-
B-cell chronic lymphocytic leukaemia lymphocyte
Manually annotated by BRENDA team
-
high enzyme expression
Manually annotated by BRENDA team
-
enzyme activity increases up to 3fold when cells start to proliferate
Manually annotated by BRENDA team
-
activity increases within 36 h of growth compared to resting cells
Manually annotated by BRENDA team
-
very low enzyme expression
Manually annotated by BRENDA team
-
very low enzyme expression
Manually annotated by BRENDA team
-
pancreatic cancer tissue, enzyme detected in 40 out of 44 patient samples
Manually annotated by BRENDA team
-
gemcitabine-resistant pancreatic cancer cell
Manually annotated by BRENDA team
-
deoxycytidine kinase activty is about 10fold lower compared with other tissues
Manually annotated by BRENDA team
-
; low enzyme activity; vastus
Manually annotated by BRENDA team
-
cells irradiated in the late exponential growth phase for experiments
Manually annotated by BRENDA team
-
; suspension culture
Manually annotated by BRENDA team
-
lymphocyte
Manually annotated by BRENDA team
additional information
-
very low activity in normal spleens and placentas
Manually annotated by BRENDA team
additional information
-
tissue specific enzyme expression
Manually annotated by BRENDA team
additional information
-
enzyme level in case of acute myeloid leukemia and acute lymphoblastic leukemia in 97 patients, expression levels in different cancer cells, overview
Manually annotated by BRENDA team
additional information
-
high enzyme expression level in case of acute myeloid leukemia and acute lymphoblastic leukemia, sensitivity of cell types to cytarabine, overview
Manually annotated by BRENDA team
additional information
-
enzyme expression throughout the cell cycle, tissue-specific expression
Manually annotated by BRENDA team
additional information
-
expression of mRNA in all tissues examined, with 5- to 10fold variation
Manually annotated by BRENDA team
additional information
-
enzyme activity tissue distribution analysis, overview
Manually annotated by BRENDA team
additional information
-
dCK-negative L1210-10K tumors
Manually annotated by BRENDA team
additional information
Mus musculus C57BL/6J
-
dCK-negative L1210-10K tumors
-
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
2 isozymes: I and II
Manually annotated by BRENDA team
-
native enzyme, perinuclear and cellular membrane area
Manually annotated by BRENDA team
-
native enzyme
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
-
-
Manually annotated by BRENDA team
-
only when overexpressed
Manually annotated by BRENDA team
-
enzyme possesses a nuclear localization signal at the N-terminus
Manually annotated by BRENDA team
-
main localization of both wild-type and mutant S74E mimicking phosphorylated enzyme
Manually annotated by BRENDA team
additional information
-
subcellular distribution
-
Manually annotated by BRENDA team
additional information
-
the enzyme possesses a nuclear import signal sequence
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
56000
-
-
gel filtration, equilibrium density and sucrose density gradient centrifugation
59300
-
-
sedimentation equilibrium determination, PAGE, both in the presence of protease inhibitors
60000
-
-
gel filtration
60000
-
-
gel filtration
60000
-
-
sedimentation equilibrium
61000
-
-
gel filtration, glycerol gradient centrifugation
68000
-
-
-
68000
-
-
gel filtration
70000
-
-
human cytoplasmic isozymes
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 52000, SDS-PAGE, T-ALL, B-CLL, AML, CML cells, x * 30000, SDS-PAGE, AML, CML, B-ALL, MOLT-4 cells
?
-
x * 30000, SDS-PAGE
dimer
-
1 * 27200 + 1 * 29000, SDS-PAGE, heterodimers in quarternary structure
dimer
-
2 * 30500, SDS-PAGE
dimer
-
-
dimer
-
2 * 30000, SDS-PAGE
dimer
-
2 * 30000, SDS-PAGE
dimer
-
crystal structure analysis
dimer
-
2 * 30500, calculated from the deduced amino acid sequence, crystal structure analysis
dimer
-
2 * 34000, SDS-PAGE, native mass by gel filtration
dimer
Lactobacillus acidophilus R-26
-
1 * 27200 + 1 * 29000, SDS-PAGE, heterodimers in quarternary structure
-
monomer
-
1 * 52000, SDS-PAGE, mitochondrial isozyme
monomer
-
-
additional information
-
3D-structure analysis, dCK structure model, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phosphoprotein
-
inactivation of purified enzyme by protein phosphatases
phosphoprotein
-
activation of enzyme is mediated by phosphorylation
phosphoprotein
-
no changes in kinetic parameters of recombinant enzyme after treatment with protein kinases A or C
phosphoprotein
-
phosphorylation of the enzyme involved in the regulation of enzyme activity
phosphoprotein
-
interindividual variability in deoxycytidine kinase activity is related to its phosphorylation level on residue Ser74; regulation of activity by phosphorylation of Ser-74
phosphoprotein
-
at least four residues phosphorylated, Thr-3, Ser-11, Ser-15, and Ser-74, Ser-74 phosphorylation level important for enzyme activity
phosphoprotein
-
phosphorylation at residue S74
phosphoprotein
-
phosphorylation of deoxycytidine kinase on Ser74 increases the enzyme activity, increasing dCK activity via Ser74 phosphorylation, e.g. by aphidicolin, can enhance the intracellular activation of some nucleoside analogs, like gemcitabine, but not of cladribine or fludarabine, overview
phosphoprotein
-
kinetic properties of the enzyme are modulated in vivo by phosphorylation of Ser74, conformational changes and mechanism, overview
phosphoprotein
-
the ataxia-telangiectasia-mutated kinase phosphorylates the enzyme on Ser74 to activate it in response to DNA damage, required in vivo and in vitro. Ser74 phosphorylation is required for initiation of the G2/M checkpoint
phosphoprotein
-
the enzyme contains four in vivo phosphorylation sites: Thr3, Ser11, Ser-15, and Ser74. Phosphorylation of Ser74, the major phosphorylated residue, strongly influences dCK activity in vivo. Phosphorylation of the three other sites, located in the N-terminal extremity of the protein, does not significantly modify enzyme activity, but phosphorylation of Thr3 can promote enzyme stability
additional information
-
posttranscriptional regulation of the enzyme
additional information
-
a posttranslational modification is suggested to be responsible for the UV-C light irradiation induced activation of the enzyme activity
additional information
-
irradiation induced phosphorylation suggested to be involved in the regulation of enzyme activity
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
crystal structure model construction, using the crystal structure of deoxyguanosine kinase, EC 2.7.1.113, as a template, for docking simulations of enzyme with purine nucleosides and analogues, overview
-
dCK in complex with acyclovir at the nucleoside phosphoryl acceptor site, and UDP at the phosphoryl donor site, hanging drop vapour diffusion method, 20 mg/ml protein with 5 mM UDP and 5 mM acyclovir is mixed with reservoir solution containing 0.90-1.5 M trisodium citrate dihydrate and 100 mM HEPES, pH 7.5, 12C, X-ray diffraction structure determination and analysis at 2.1 A resolution, molecular replacement
-
enzyme mutant C9S/C45S/C59S/S74E/R104M/D133A/C146S in complex with L-dT and UDP, hanging drop vapour diffusion method, mixing of 0.001 ml of 9-15 mg/ml protein mixed with 0.001 ml reservoir solution containing 0.9-1.5 M trisodium citrate dihydrate and 100 mM Tris, pH 7.5, room temperature, X-ray diffraction structure determination and analysis at 1.9-2.5 A resolution
-
hanging drop vapour diffusion method, in complex with 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-9H-purin-6-amine and ADP
-
hanging drop vapour diffusion method, in complex with deoxycytidine (dC) and UDP, and in the presence of deoxycytidine but the absence of UDP or ADP
-
hanging drop vapour diffusion method, mutant enzyme crystallized in complex with its substrates (-)-beta-2,3-dideoxy-3-thiacytidine and troxacitabine; mutant C9S/C45S/C59S/C146S in complex with L-nucleosides (-)-beta-2',3'-dideoxy-3'-thiacytidine and troxacitabine. The nucleoside binding-site tolerates substrates with different chiral configurations by maintaining virtually all of the protein-ligand interactions responsible for productive substrate positioning. The pseudo-symmetry of nucleosides and nucleoside analogs in combination with their conformational flexibility allows the L- and D-enantiomeric forms to adopt similar shapes when bound to the enzyme
-
in complex with dCMP, UDP, and Mg2+ ion, as well as with dAMP, UDP and Mg2+ ion, both to 3.4 A resolution. Product complexes with UDP and a dead-end complex with substrate and UDP have similar active-site conformations
-
mutant C9S/C45S/C59S/C146S in complex with D-2'-deoxycytidine and ADP, L-2'-deoxycytidine and ADP, and with 5-fluoro-1-(2R,5S)-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine, i.e. emtricitabine, and ADP. The ability of deoxycytidine kinase to phosphorylate the beta-form of enantiomeric nucleosides is due to both the nature of the enzymes active site and the nature of the substrates. Most of the binding interactions between substrate and enzyme are directed at the base moiety of the nucleoside
-
mutant enzyme R104M/D133A in complex with L-thymidine, hanging drop vapor diffusion method, using 0.90-1.5 M trisodium citrate dihydrate and 100 mM HEPES, pH 7.5
-
purified recombinanat Wild-type enzyme in complex with 5-methyldeoxycytidine and ADP, hanging drop vapour diffusion method, mixing of 0.001 ml of 8 mg/ml protein mixed with 0.001 ml reservoir solution containing 0.9-1.5 M trisodium citrate dihydrate and 100 mM Tris, pH 7.5, room temperature, X-ray diffraction structure determination and analysis at 1.96 A resolution
-
structural studies of ternary complexes. The enzyme conformation adjusts to the different hydrogen-bonding properties between 2'-deoxyadenosine and 2'-deoxyguanosine and to the presence of substituent at the 2-position present in 2'-deoxyguanosine and cladribine. The carbonyl group in 2'-deoxyguansoine elicits a conformational adjustment of the active site residues Arg104 and Asp133. 2'-Deoxyguanosine and cladribine adopt the anti conformation, in contrast to the syn conformation observed with 2'-deoxyadenosine
-
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6
-
-
t1/2: 2 min at 60C
8
-
-
moderately stable, t1/2: 7.9 min at 60C
10
-
-
unstable at 60C
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
22
-
-
at least 24 h, in the presence of dithiothreitol
37
-
-
at least 6 h stable
50
-
-
10 min, 10% loss of activity
54
-
-
inactivation
60
-
-
10 min, about 65% loss of activity
60
-
-
dCTP enhances heat stability at pH 6, dithiothreitol slightly, not deoxycytidine or other nucleosides; t1/2: 7.9 min at pH 8, t1/2: 2 min at pH 6, unstable at pH 10
60
-
-
ATP, dCTP or glycerol stabilizes against heat inactivation; t1/2: 7.9 min at pH 8, t1/2: 2 min at pH 6, unstable at pH 10
additional information
-
-
temperature stability of deoxycytidine kinase activity differs appreciably from deoxyadenosine kinase activity
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
2-mercaptoethanol stabilizes
-
bovine serum albumin stabilizes
-
dithiothreitol stabilizes
-
SH-reducing agents stabilize
-
bovine serum albumin stabilizes
-
dithiothreitol, MgCl2, ATP, KCl and glycerol stabilize
-
dTTP, ATP or deoxycytidine stabilizes
-
very unstable at low protein concentrations
-
bovine serum albumin does not stabilize
-
dithiothreitol stabilizes
-
protamine treatment, MnCl2-treatment or ammonium sulfate fractionation inactivates during purification
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C, in 5 mM DTT and 50% glycerol, stable
-
-30C, several months in the presence of 2-mercaptoethanol
-
4C, if purified in the absence of 2-mercaptoethanol it loses most of its activity within 2 days, DTT restores
-
dithiothreitol is more effective than 2-mercaptoethanol in stabilizing during storage
-
-70C, concentrated enzyme solution in Tris-buffer with MgCl2 and mercaptoethanol, at least 12 months
-
-85C, in 1 mg/ml bovine serum albumin, 20% v/v glycerol, 0.2 M potassium phosphate, 2 mM ATP, 2.4 mM MgCl2 and 0.025 M DTT, more than 12 months
-
4C, concentrated enzyme solution in Tris-buffer with MgCl2 and mercaptoethanol, at least 2 weeks
-
4C, t1/2: 7 days with and t1/2: 72 h without bovine serum albumin
-
-20C, 3 months
-
4C, at least 1 week
-
glycerol, bovine serum albumin, 2-mercaptoethanol or EDTA does not enhance storage stability
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
affinity chromatography
-
preparative PAGE
-
affinity chromatography
-
affinity chromatography; mitochondrial isozyme (extracted with digitonin); partial
-
affinity chromatography; spleen
-
Ni-NTA column chromatography, gel filtration
-
partial
-
recombinant enzymes using His-tag
-
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain C41(DE3) by nickel affinity chromatography and gel filtration
-
recombinant protein from Escherichia coli
-
recombinant protein using His-tag
-
affinity chromatography
-
partial
-
spleen
-
affinity chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
DNA and amino acid sequence determination and analysis, transient expression of His-tagged wild-type and mutants in HEK 293T cells
-
expressed as His-tag fusion protein in Escherichia coli BL21(DE3)
-
expressed as His-tag fusion protein in HEK293T cells
-
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Escherichia coli C41 (DE3) cells
-
expressed in HEK 293T cells
-
expressed of engineered protein as His-tag fusion protein in Escherichia coli
-
expression in Cos-1 cells
-
expression in Escherichia coli
-
expression in Escherichia coli and in HEK-293 cell
-
expression in murine GI261, rat C6 and human U373 cell
-
expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain C41(DE3)
-
genetic organization, located on chromosome 4q13.3-4q21.1, expression as GFP-fusion protein with location in the nucleus
-
mutant protein expressed in Escherichia coli
-
native and mutant proteins expressed as His-tag fusion proteins in Escherichia coli BL21(DE3)pLysS
-
native and mutant proteins expressed in Escherichia coli BL21 star
-
overexpression of wild-type and mutant enzymes in Jurkat, Molt-4, and U87-MG cells
-
quantitative real-time-PCR
-
quantitative RT-PCR enzyme expression analysis in Saos-2 cells and OCI-AML3 cells, and overexpression of wild-type and mutant enzymes in Saos2 cells, overview
-
quantitative RT-PCR expression analysis
-
the single copy gene is located on chromosome 4q13.3-q21.1
-
quantitative RT-PCR expression analysis
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
RNA-binding protein HuR silencing reduces dCK protein expression in pancreatic cancer cells
-
paclitaxel significantly decreases dCK mRNA and protein levels in H460 and H520 cells
-
RNA-binding protein HuR overexpression elevates dCK protein expression in pancreatic cancer cells
-
the enzyme is hypoxia-induced
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
A100V/R104M/D133A
-
site-directed mutagenesis, mutations alter the residues to the multisubstrate nucleoside kinase, EC 2.7.1.145, mutant shows 30fold increased kcat for deoxycytidine compared to the wild-type enzyme
A100V/R104M/D133A
-
12fold increase in ratio kcat/Km for deoxycytidine
A100V/R104M/D133S
-
6fold increase in ratio kcat/Km for deoxycytidine
A100V/R104M/D133T
-
ratio kcat/Km for deoxycytidine similar to wild-type
A119G
-
genetic polymorphism, 66% of wild-type activity, decrease in Km value; naturally occurring mutation, 66% of activity of the wild type protein
C146A
-
very low activity
C185A
-
lower efficiency with dCyd as the substrate with ATP und UTP, nearly 2-fold higher efficiency than wild-type dCK with dAdo as substrate and UTP as the phosphate donor
C9S/C45S/C59S/C146S
-
engineered protein has a significantly improved crystallization behaviour compared with the wild type protein; mutation of the four surface-exposed Cys residues, constructued for crystallization. Mutant displays moderate kinetic differences in the catalytic efficiency when compared with wild-type
C9S/C45S/C59S/C146S
-
mutation of the four surface-exposed Cys residues, constructued for crystallization. Mutant displays moderate kinetic differences in the catalytic efficiency when compared with wild-type
C9S/C45S/C59S/S74E/R104M/D133A/C146S
-
site-directed mutagenesis, crystallization mutant
D133A
-
site-directed mutagenesis, the mutation renders the enzyme capable of thymidine binding
D133A
-
site-directed mutagenesis, the mutant is active with thymidine derivatives, in contrast to the wild-type enzyme
D47E/R104Q/D133G/N163I/F242L
-
1.5fold increase in ratio kcat/Km for deoxycytidine
DEL65-79
-
construction of an enzyme variant lacking a flexible insert (residues 65-79) but having similar catalytic properties as the wild type
P122S
-
genetic polymorphism, 43% of wild-type activity, decrease in Km value; naturally occurring mutation, 43% of activity of the wild type protein
P122S
-
the mutant shows reduced enzyme activity
R104I/D133A
-
site-directed mutagenesis, the mutations render the enzyme active with 5-substituted deoxycytidine and thymidine, altered substrate specificity compared to the wild-type enzyme
R104L/D133A
-
the double mutant does also accept L- and D-thymidine as substrates
R104L/D133A
-
site-directed mutagenesis, the mutations render the enzyme active with 5-substituted deoxycytidine and thymidine, altered substrate specificity compared to the wild-type enzyme
R104M
-
site-directed mutagenesis, the mutation renders the enzyme capable of thymidine binding
R104M
-
site-directed mutagenesis, the mutant is active with thymidine derivatives, in contrast to the wild-type enzyme
R104M/D133A
-
site-directed mutagenesis, mutations alter the residues to the multisubstrate nucleoside kinase, EC 2.7.1.145, the mutant gains the ability to phosphorylate deoxythymidine
R104M/D133A
-
4fold increase in ratio kcat/Km for deoxycytidine
R104M/D133A
-
the double mutant is a pyrimidine-specific enzyme due to large Km values with purines and does also accept L- and D-thymidine as substrates
R104M/D133A
-
site-directed mutagenesis, the mutations render the enzyme active with 5-substituted deoxycytidine and thymidine, altered substrate specificity compared to the wild-type enzyme
R104M/D133A/S74E
-
site-directed mutagenesis, the mutant is active with thymidine derivatives, in contrast to the wild-type enzyme
R104M/D133N
-
3fold increase in ratio kcat/Km for deoxycytidine
R104M/D133S
-
6fold increase in ratio kcat/Km for deoxycytidine
R104M/D133T
-
mutant with reversed substrate specificity, with elevated specific constant for thymidine phosphorylation and decreased activity for deeoxycytidine, deoxyadenosine, and deoxyguanosine
R104Q/D133A
-
site-directed mutagenesis, the mutations render the enzyme active with 5-substituted deoxycytidine and thymidine, altered substrate specificity compared to the wild-type enzyme
R104Q/D133G
-
mutant is a generalist kinase with broader specificity and elevated turnover compared with wild-type
R104Q/D133N
-
1.5fold increase in ratio kcat/Km for deoxycytidine
S11A
-
no significant effect on activity
S11A
-
site-directed mutagenesis, replacement of the phosphorylation site
S11E
-
no significant effect on activity
S11E
-
site-directed mutagenesis, replacement of the phosphorylation site
S15A
-
no significant effect on activity
S15A
-
site-directed mutagenesis, replacement of the phosphorylation site
S15E
-
no significant effect on activity
S15E
-
site-directed mutagenesis, replacement of the phosphorylation site, the mutant shows a slight, but significant, reduction of Ser74 phosphorylation
S74A
-
mutation markedly decreases activity
S74A
-
6-8fold lower activity than wild-type
S74A
-
site-directed mutagenesis
S74D
-
2-4fold lower kcat values
S74E
-
mutation does not significantly modify dCK activity
S74E
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mutation mimicking phosphorylation, results in 11fold increase in kcat value for deoxycytidine. Mutation has no effect on cellular localization
S74E
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site-directed mutagenesis, the mutation sensitizes the enzyme to feedback inhibition by dCTP, regardless of the phosphoryl donor. Mimicking Ser74 phosphorylation by a S74E mutation increases the enzyme activity toward pyrimidine analogues. The S74E mutation increased the kcat for cladribine by 8 or 3fold, depending on whether the phosphoryl donor was ATP or UTP, for clofarabine by about 2fold with both ATP and UTP, and for fludarabine by 2fold, but only with UTP
S74E
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site-directed mutagenesis, replacing the serine with a glutamic acid mimic phosphorylation of Ser74, the enzyme containing the S74E mutation adopts the open state, but wild-type dCK can adopt the open state also in the absence of the S74E mutation
S74E
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site-directed mutagenesis, the mutant is active with thymidine derivatives, in contrast to the wild-type enzyme
S74E
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site-directed mutagenesis
S74Q
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no significant change in kcat for any of the substrates tested
T3A
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no significant effect on activity
T3A
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site-directed mutagenesis, replacement of the phosphorylation site, the mutant shows a slight, but significant, reduction of Ser74 phosphorylation
T3E
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no significant effect on activity
I24V
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genetic polymorphism, 85% of wild-type activity; naturally occurring mutation, 85% of activity of the wild type protein
additional information
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sequencing of gene from European and African individuals reveals 64 genetic polymorphisms. In general, African ancestry subjects show higher mRNA expression compared with subjects with European ancestry. In both groups, single nucleotide polymorphism 35708 C>T of a 3'-untranslated region is significanlty associated with lower mRNA expression and with lower blast 1-beta-D-arabinofuranosylcytosine 5'-triphosphate levels in acute myeloid leukemia patients
additional information
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in gemcitabine-resistant pancreatic cancer cells, expression of deoxycytidine kinase is significantly reduced compared with that of parental cells. Treatment with siRNA targeted to deoxycytidine kinase reduces gemcitabine sensitivity without affecting cell proliferation. Downregulation of gemcitabine-related genes RRM1 and RRM2 by siRNA increases gemcitabine sensitivity and reduces cell proliferation even without gemcitabine treatment
additional information
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R104 and D133 are key residues for substrate specificity
additional information
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sequencing of deoxycytidine kinase and cytidine monophosphate kinase using 240 DNA samples reveals 28 polymorphisms in deoxycytidine kinase. Variant allozyme enzyme activities range from 32% to 105% of the wild type activity with no significant differences in apparent Km values except for a V24/S122 double variant enzyme. Relative levels of immunoreactive protein after expression in COS-1 cells parallel relative levels of enzyme activity
additional information
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cotruction of a loss-of--function mutant dCK containing an altered ATP-binding site
additional information
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mutants of dCK with rationally designed active sites, that make them thymidine-activating, are stably introduced into cells by recombinant lentiviral vectors. Transduced cells maintain growth kinetics and function. These dCK mutants efficiently activate bromovinyl-deoxyuridine, L-deoxythymidine, and L-deoxyuridine, which are otherwise not toxic to wild-type cells, overview. Mutant dCK-expressing Jurkat, Molt-4, and U87-MG cells could be efficiently eliminated in vitro and in xenogeneic leukemia and tumor models in vivo
additional information
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stable enzyme knockout in HeLa cells by expression of dCK-siRNA or shRNA
T3E
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site-directed mutagenesis, replacement of the phosphorylation site, the mutant shows a slight, but significant, reduction of Ser74 phosphorylation
additional information
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for enzyme knockout, MLE12 cells are transfected with DCK siRNA
additional information
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deletion of exon 3 inactivates dCK function. Generation of enzyme knockout mice that show 90fold decrease in thymic cellularity compared to wild-type, lymphocyte numbers in the dCK KO mice are 5 to 13fold below normal values
Renatured/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
after elution from Sephadex column, reactivation by incubation with 50 mM dithiothreitol and 1 mg/ml bovine serum albumin
-
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
analysis
-
deoxycytidine kinase from B-cell chronic lymphocytic leukaemia lymphocytes can be detected by use of anti-phospho-ser74 antibodies
medicine
-
direct inhibition of DNA polymerases by aphidicolin stimulated enzyme in normal, acute myeloid leukaemic and HL60 promyelocytic cells
medicine
-
enzyme is active and important in anticancer and antiviral therapy due to high phosphorylation activity of prodrugs, overview
medicine
-
interindividual variability in deoxycytidine kinase activity is related to its phosphorylation level on residue Ser74
medicine
-
sequencing of gene from European and African individuals reveals 64 genetic polymorphisms. In general, African ancestry subjects show higher mRNA expression compared with subjects with European ancestry. In both groups, single nucleotide polymorphism 35708 C>T of a 3'-untranslated region is significantly associated with lower mRNA expression and with lower blast 1-beta-D-arabinofuranosylcytosine 5'-triphosphate levels in acute myeloid leukemia patients
medicine
-
in gemcitabine-resistant pancreatic cancer cells, expression of deoxycytidine kinase is significantly reduced compared with that of parental cells. Treatment with siRNA targeted to deoxycytidine kinase reduces gemcitabine sensitivity without affecting cell proliferation. Downregulation of gemcitabine-related genes RRM1 and RRM2 by siRNA increases gemcitabine sensitivity and reduces cell proliferation even without gemcitabine treatment
medicine
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deoxycytidine kinase overexpression substantially increases both the toxic and radiosensitizing effects of gemcitabine. Enhancement is mild in murine GI261 cells and much stronger in rat C6 and human U373 cells. Combination of enzyme overexpression, gemcitabine treatment and irradiation improves the survival rate of C6 cell bearing rats significantly
medicine
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thymocytes lacking adenosine deaminase activity accumulate intracellular dATP and undergo apoptosis. Inhibition of deoxycytidine kinase prevents the accumulation of dATP and induction of apoptosis to a large degree, inhibition of both deoxycytidine kinase and adenosine kinase completely abrogates accumulation of dATP and significantly reduces the induction of apoptosis
pharmacology
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the enzyme is a critical determinant of therapeutic activity for several nucleoside analogue prodrugs
medicine
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recombinant enzyme in human A-549 lung carcinoma cells or murine NIH3T3 fibroblast cells, increase in cytotoxicity of cytosine arabinoside, 5'-aza-2'-deoxycytidine, decrease in toxicity of 2',2'-difluorodeoxycytidine
pharmacology
-
the enzyme is a critical determinant of therapeutic activity for several nucleoside analogue prodrugs
pharmacology
Mus musculus C57BL/6J
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the enzyme is a critical determinant of therapeutic activity for several nucleoside analogue prodrugs
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medicine
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ability of the designer enzymes to activate 5-substitued pyrimidines makes it possible to utilize such nucleoside analogs in suicide gene therapy or protein therapy applications that target cancer cells
additional information
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deoxycytidine kinase is a key enzyme in the activation of several therapeutic nucleoside analogues