Information on EC 2.7.1.113 - deoxyguanosine kinase

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

EC NUMBER
COMMENTARY
2.7.1.113
-
RECOMMENDED NAME
GeneOntology No.
deoxyguanosine kinase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + deoxyguanosine = ADP + dGMP
show the reaction diagram
sequential Bi Bi mechanism
-
ATP + deoxyguanosine = ADP + dGMP
show the reaction diagram
active site residues are Glu70, Lys142, and Arg142
-
ATP + deoxyguanosine = ADP + dGMP
show the reaction diagram
substrate interactions and binding mechanism, and active site structure
-
ATP + deoxyguanosine = ADP + dGMP
show the reaction diagram
substrate interactions, reaction mechanism
Q16854
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Metabolic pathways
-
-
purine deoxyribonucleosides salvage
-
-
Purine metabolism
-
-
purine metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:deoxyguanosine 5'-phosphotransferase
Deoxyinosine can also act as acceptor.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
(dihydroxypropoxymethyl)guanine kinase
-
-
-
-
2'-deoxyguanosine kinase
-
-
-
-
deoxyadenosine kinase/deoxyguanosine kinase
-
abbrevation: dAK/dGK
deoxyadenosine kinase/deoxyguanosine kinase
Lactobacillus acidophilus R-26
-
abbrevation: dAK/dGK
-
deoxyguanosine kinase
-
-
deoxyguanosine kinase
-
-
DG kinase
-
-
DGUOK
Q16854
-
kinase, deoxyguanosine (phosphorylating)
-
-
-
-
NTP-deoxyguanosine 5'-phosphotransferase
-
-
-
-
nucleoside triphosphate: deoxyguanosine 5'-phosphotransferase
-
-
nucleoside triphosphate: deoxyguanosine 5'-phosphotransferase
Q16854
-
CAS REGISTRY NUMBER
COMMENTARY
39471-28-8
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
; gene yaaG
-
-
Manually annotated by BRENDA team
calf
-
-
Manually annotated by BRENDA team
; 3 patients, one with N46S/L266R double mutation who is clinically healthy at age of 10 years, 2 patients with lethal mutations who died at 2 and 3 month of age and parents and healthy controls
-
-
Manually annotated by BRENDA team
constitutive expression
SwissProt
Manually annotated by BRENDA team
patient with mitochondrial DNA depletion syndrome
-
-
Manually annotated by BRENDA team
strain R-26, heterodimeric enzyme, deoxyadenosine kinase/deoxguanosine kinase
-
-
Manually annotated by BRENDA team
strain R-26, heterodimeric enzyme, deoxyadenosine kinase/deoxguanosine kinase, i.e. dAK/dGK
UniProt
Manually annotated by BRENDA team
Lactobacillus acidophilus R-26
strain R-26, heterodimeric enzyme, deoxyadenosine kinase/deoxguanosine kinase
-
-
Manually annotated by BRENDA team
Lactobacillus acidophilus R-26
strain R-26, heterodimeric enzyme, deoxyadenosine kinase/deoxguanosine kinase, i.e. dAK/dGK
UniProt
Manually annotated by BRENDA team
3 days old
-
-
Manually annotated by BRENDA team
cytosolic deoxyguanosine kinase 2, amino-terminally truncated isoform; mitochondrial deoxyguanosine kinase 1
SwissProt
Manually annotated by BRENDA team
piglet
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
deoxyguanosine kinase deficiency is the commonest type of mitochondrial DNA depletion associated with a hepatocerebral phenotype, deoxyguanosine kinase deficiency is associated with a variable clinical phenotype, long-term survival is best predicted by the absence of profound hypotonia, significant psychomotor retardation, or nystagmus. In the presence of these features, there is increased mortality, and liver transplantation does not confer increased survival
malfunction
-
dGK depletion in cells results in lower sensitivity to 2-fluoro-9-beta-D-arabinofuranosyladenine, gemcitabine, clofarabine, and 9-beta-D-arabinofuranosylguanine, but slightly higher sensitivity to cladribine and cytarabine
malfunction
-
mitochondrial DNA depletion due to deoxyguanosine kinase deficiency is a devastating mitochondrial disease of infancy characterized by liver failure and encephalopathy and invariably a fatal outcome. The cytoplasmic deoxycytine kinase supplemented with external substrates may compensate for the deficient deoxyguanosine kinase
malfunction
-
mutations in deoxyguanosine kinase cause mitochondrial DNA depletion and a clinical phenotype that consists of neonatal liver failure, nystagmus, and hypotonia
malfunction
-
deoxyguanosine kinase deficiency associated with mutations in the deoxyguanosine kinase gene is responsible for hepatic mitochondrial depletion syndrome phenotype, the disease is characterized by tissue-specific pathology. Deoxyguanosine kinase gene mutations combined with impaired glucose homeostasis and iron overload features cause lethal progressive liver failure in infants
malfunction
-
loss of enzyme function results in the depletion of mitochondrial DNA relative to nuclear DNA. Recessive deoxyguanosine kinase deficiency causes juvenile onset mitochondrial myopathy and is the cause of an infantile onset hepatocerebral mitochondrial disease including significant hepatic failure with nystagmus and hypotonia. Mitochondrial DNA depletion in cells from a patient presenting with mitochondrial myopathy caused by a mutation in the enzyme
physiological function
-
deoxyguanosine kinase is responsible for phosphorylation of purine deoxyribonucleosides in the mitochondrial matrix. The main supply of purine dNTPs for mtDNA synthesis comes from the salvage pathway initiated by the enzyme
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2'-deoxyadenosine-3'-fluoro-3'-triphosphate + 2'-deoxyguanosine
2'-deoxyadenosine-3'-fluoro-3'-diphosphate + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
2'-deoxyadenosine-3'-fluoroara-3'-triphosphate + 2'-deoxyguanosine
2'-deoxyadenosine-3'-fluoroara-3'-diphosphate + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
low activity
-
-
?
2'-deoxyadenosine-3'-triphosphate + 2'-deoxyguanosine
2'-deoxyadenosine-3'-diphosphate + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
3'-deoxyadenosine-2'-triphosphate + 2'-deoxyguanosine
3'-deoxyadenosine-2'-diphosphate + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
3'-deoxyadenosine-3'-fluoro-2'-triphosphate + 2'-deoxyguanosine
3'-deoxyadenosine-3'-fluoro-2'-diphosphate + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
3'-deoxyadenosine-3'-fluoroxylo-2'-triphosphate + 2'-deoxyguanosine
3'-deoxyadenosine-3'-fluoroxylo-2'-diphosphate + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 1-(2-deoxy-beta-D-ribofuranosyl)-7-iodoisocarbostyril
ADP + ?
show the reaction diagram
-
4.4% of the activity with 2'-deoxyguanosine
-
-
?
ATP + 1-(2-deoxy-beta-D-ribofuranosyl)-isocarbostyril
ADP + ?
show the reaction diagram
-
poor substrate, 1.1% of the activity with 2'-deoxyguanosine
-
-
?
ATP + 1-beta-D-arabinofuranosyladenine
ADP + 1-beta-D-arabinofuranosyladenine 5'-phosphate
show the reaction diagram
Q16854
-
-
-
?
ATP + 2',2'-difluorodeoxyguanosine
ADP + 2',2'-difluorodeoxyguanosine 5'-monophosphate
show the reaction diagram
Q9QX60
recombinant mitochondrial deoxyguanosine kinase, 147% of activity with deoxyguanosine
-
-
ATP + 2',2'-difluorodeoxyguanosine
ADP + 2',2'-difluorodeoxyguanosine 5'-phosphate
show the reaction diagram
Q16854
-
-
-
?
ATP + 2',3'-dideoxyguanosine
ADP + 2',3'-dideoxyguanosine 5'-monophosphate
show the reaction diagram
-
recombinant deoxyguanosine kinase, 14% of activity with deoxyguanosine
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
Q16854
-
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
key enzyme in mitochondrial DNA precursor 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
-
-
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
-
-
-
ir
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
Q16854
-
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
key enzyme in mitochondrial DNA precursor synthesis
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
important enzyme for the phosphorylation/activation of 2'-deoxyguanosine
-
-
ir
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
one of the two mitochondrial deoxynucleoside salvage pathway enzymes involved in precursor synthesis for mitochondrial DNA replication, DGUOK is responsible for the initial rate-limiting phosphorylation of the purine deoxynucleosides, mutations of the enzyme are associated with the hepato-specific and hepatocerebral forms of the mtDNA depletion syndrome
-
-
?
ATP + 2'-deoxyinosine
ADP + 2'-deoxyinosine 5'-phosphate
show the reaction diagram
Q16854
-
-
-
?
ATP + 2'-deoxyinosine
ADP + 2'-deoxyinosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine
ADP + 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine 5'-monophosphate
show the reaction diagram
-
recombinant mitochondrial deoxyguanosine kinase
-
?
ATP + 2-chloro-2'-arabinofluoro-2'-deoxyadenosine
ADP + 2-chloro-2'-arabinofluoro-2'-deoxyadenosine 5'-phosphate
show the reaction diagram
Q16854
-
-
-
?
ATP + 2-chloro-2'-deoxyadenosine
ADP + 2-chloro-2'-deoxyadenosine monophosphate
show the reaction diagram
-
-
-
-
ATP + 2-chloro-2'-deoxyadenosine
ADP + 2-chloro-2'-deoxyadenosine monophosphate
show the reaction diagram
-
recombinant mitochondrial deoxyguanosine kinase
-
?
ATP + 2-chloro-2'-deoxyadenosine
ADP + 2-chloro-2'-deoxyadenosine monophosphate
show the reaction diagram
Q9QX60
recombinant mitochondrial deoxyguanosine kinase, 200% of activity with deoxyguanosine at 0.005 mM
-
?
ATP + 2-chlorodeoxyadenosine
ADP + 2-chlorodeoxyadenosine 5'-phosphate
show the reaction diagram
Q16854
-
-
-
?
ATP + 2-chlorodeoxyadenosine
ADP + 2-chlorodeoxyadenosine 5'-monophosphate
show the reaction diagram
-
-
-
-
?
ATP + 2-fluoro-arabinosyl-adenine
ADP + 2-fluoro-arabinosyl-adenine 5'-monophosphate
show the reaction diagram
-
recombinant mitochondrial deoxyguanosine kinase
-
?
ATP + 2-fluoroadenine-beta-D-arabinofuranoside
ADP + 2-fluoroadenine-beta-D-arabinofuranoside 5'-monophosphate
show the reaction diagram
-
-
-
-
?
ATP + 3'-fluoro-2',3'-dideoxyguanosine
ADP + 3'-fluoro-2',3'-dideoxyguanosine 5'-monophosphate
show the reaction diagram
-
recombinant deoxyguanosine kinase, 14% of activity with deoxyguanosine
-
?
ATP + 9-(1,3-dihydroxy-2-propoxymethyl)guanine
ADP + 9-(1,3-dihydroxy-2-propoxymethyl)guanine 5'-monophosphate
show the reaction diagram
-
antiherpesvirus drug ganciclovir, recombinant mitochondrial deoxyguanosine kinase, 6% of activity with deoxyguanosine
-
?
ATP + 9-(4-hydroxy-3-hydroxymethylbutyl-1-yl)guanine
ADP + 9-(4-hydroxy-3-hydroxymethylbutyl-1-yl)guanine 5'-monophosphate
show the reaction diagram
-
antiherpesvirus drug penciclovir, recombinant mitochondrial deoxyguanosine kinase, 50% of activity with deoxyguanosine
-
?
ATP + 9-beta-D-arabinofuranosylguanine
ADP + 9-beta-D-arabinofuranosylguanine 5'-monophosphate
show the reaction diagram
-
-
-
-
?
ATP + 9-beta-D-arabinofuranosylguanine
ADP + 9-beta-D-arabinofuranosylguanine 5'-monophosphate
show the reaction diagram
-
guanosine analog with activity in patients with T-cell malignancies
-
?
ATP + 9-beta-D-arabinofuranosylguanine
ADP + 9-beta-D-arabinofuranosylguanine 5'-phosphate
show the reaction diagram
Q16854
-
-
-
?
ATP + 9-beta-D-arabinosylguanine
ADP + 9-beta-D-arabinosylguanine 5'-monophosphate
show the reaction diagram
-
-
-
?
ATP + arabinosyl adenine
ADP + arabinosyl adenine 5'-monophosphate
show the reaction diagram
-
recombinant mitochondrial deoxyguanosine kinase, very low activity
-
?
ATP + arabinosyl guanine
ADP + arabinosyl guanine 5'-monophosphate
show the reaction diagram
-
recombinant mitochondrial deoxyguanosine kinase, better substrate than deoxyguanosine kinase
-
?
ATP + cytarabine
ADP + cytarabine 5'-monophosphate
show the reaction diagram
-
-
-
-
?
ATP + deoxyadenosine
ADP + dAMP
show the reaction diagram
-
recombinant mitochondrial deoxyguanosine kinase
-
?
ATP + deoxyadenosine
ADP + dAMP
show the reaction diagram
-
4.8%, 25.8% and 93.5% of activity with deoxyguanosine at 0.01 mM, 0.1 mM and 1 mM deoxyguanosine, respectively
-
?
ATP + deoxyadenosine
ADP + dAMP
show the reaction diagram
-
3% of activity with deoxyguanosine
-
-
?
ATP + deoxyadenosine
ADP + dAMP
show the reaction diagram
Q9QX60
recombinant mitochondrial deoxyguanosine kinase, very low activity
-
?
ATP + deoxyadenosine
ADP + dAMP
show the reaction diagram
Q54UT2
barely measurable phosphorylation of deoxyadenosine
-
-
?
ATP + deoxycytidine
ADP + dCMP
show the reaction diagram
-
-
-
-
?
ATP + deoxycytidine
ADP + dCMP
show the reaction diagram
-
recombinant mitochondrial deoxyguanosine kinase
-
?
ATP + deoxycytidine
ADP + dCMP
show the reaction diagram
-
recombinant deoxyguanosine kinase, 3% of activity with deoxyguanosine
-
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
-
-
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
Q54UT2
-
-
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
Q9QX60
-
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
no activity with deoxycytidine
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
no activity with deoxycytidine
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
no activity with deoxycytidine
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
no activity with deoxycytidine
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
ATP can be replaced by dUTP
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
poor donor substrates are dATP or GTP
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
no activity with dATP and GTP
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
no activity with inosine and 9-beta-arabinofuranosyladenine
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
no activity with dATP or GTP, no activity with deoxythymidine, uridine and cytosine
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
no activity with deoxythymidine, uridine and cytosine
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
no activity with dGTP
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
no activity with dGTP
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
no activity with dGTP, ATP most efficient at pH 5.5, dTTP or UTP most efficient, i.e. more efficient than ATP, at pH 7.4, no activity with dITP
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
recombinant mitochondrial deoxyguanosine kinase does not discriminate between beta-D-2'-deoxyguanosine and beta-L-2'-deoxyguanosine
-
-
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
no activity with adenosine
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
no activity with adenosine
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
no activity with adenosine
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
ATP can be replaced by dTTP, CTP, dCTP and UTP
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
ATP can be replaced by dTTP, CTP, dCTP and UTP
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
ATP can be replaced by dTTP, CTP, dCTP and UTP
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
84%, 64%, 35% and 20% of activity with ATP with dTTP, CTP, dCTP and UTP, respectively
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
highly specific for phospho group acceptor
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
highly specific for phospho group acceptor
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
ATP twice as effective as CTP or GTP and 4 times as effective as UTP
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
enzyme of purine deoxynucleoside salvage pathway
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
first reaction in reutilization of deoxyguanosine for dGTP biosynthesis
-
?
ATP + deoxyinosine
ADP + dIMP
show the reaction diagram
-
-
-
-
-
ATP + deoxyinosine
ADP + dIMP
show the reaction diagram
-
-
-
?
ATP + deoxyinosine
ADP + dIMP
show the reaction diagram
-
recombinant mitochondrial deoxyguanosine kinase
-
?
ATP + deoxyinosine
ADP + dIMP
show the reaction diagram
-
63% of activity with deoxyguanosine
-
?
ATP + deoxyinosine
ADP + dIMP
show the reaction diagram
Q9QX60
10% of activity with deoxyguanosine
-
?
ATP + deoxyinosine
ADP + dIMP
show the reaction diagram
-
recombinant mitochondrial deoxyguanosine kinase, may be the preferred substrate in vivo
-
?
ATP + dideoxyinosine
ADP + dideoxyinosine 5'-monophosphate
show the reaction diagram
-
recombinant mitochondrial deoxyguanosine kinase, very low activity
-
?
ATP + dioxolane guanosine
ADP + dioxolane guanosine 5'-phosphate
show the reaction diagram
-
low activity, step in anabolism of amdoxovir, i.e. (-)-beta-D-2,6-diaminopurine dioxolane, a prodrug of dioxolane guanosine, 0.02% of the activity with 2'-deoxyguanosine
-
-
?
ATP + ganciclovir
ADP + ganciclovir phosphate
show the reaction diagram
Q16854
i.e. 9-(1,3-dihydroxy-2-propoxymethyl)-guanine, low activity
-
-
?
ATP + guanosine
ADP + GMP
show the reaction diagram
-
mitochondrial deoxyguanosine kinase
-
?
ATP + guanosine
ADP + GMP
show the reaction diagram
-
recombinant deoxyguanosine kinase, 7% of activity with deoxyguanosine
-
?
ATP + penciclovir
ADP + penciclovir 5'-phosphate
show the reaction diagram
Q16854
i.e. 9-(2-hydroxy-1-hydroxymethyl-ethoxymethyl)-guanine, low activity
-
-
?
CTP + 2'-deoxyguanosine
CDP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
CTP + deoxyguanosine
CDP + dGMP
show the reaction diagram
-
-
-
?
CTP + deoxyguanosine
CDP + dGMP
show the reaction diagram
-
64% of activity with ATP
-
?
CTP + deoxyguanosine
CDP + dGMP
show the reaction diagram
-
62% of activity with ATP at pH 6.0, 1.8fold higher activity than with ATP at pH 7.0
-
?
CTP + deoxyguanosine
CDP + dGMP
show the reaction diagram
-
50% of activity with ATP
-
-
?
dCTP + deoxyguanosine
dCDP + dGMP
show the reaction diagram
-
-
-
?
dCTP + deoxyguanosine
dCDP + dGMP
show the reaction diagram
-
-
-
?
dCTP + deoxyguanosine
dCDP + dGMP
show the reaction diagram
-
35% of activity with ATP
-
?
dTTP + deoxyguanosine
dTDP + dGMP
show the reaction diagram
-
-
-
?
dTTP + deoxyguanosine
dTDP + dGMP
show the reaction diagram
-
84% of activity with ATP
-
?
dTTP + deoxyguanosine
dTDP + dGMP
show the reaction diagram
-
83% of activity with ATP at pH 6.0, 2.8fold higher activity than with ATP at pH 7.0
-
?
dUTP + deoxyguanosine
dUDP + dGMP
show the reaction diagram
-
69% of activity with ATP at pH 6.0, 1.7fold higher activity than with ATP at pH 7.0
-
?
GTP + 2'-deoxyadenosine
GDP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
very low activity
-
-
?
GTP + 2'-deoxycytidine
GDP + 2'-deoxycytidine 5'-phosphate
show the reaction diagram
-
very low activity
-
-
?
GTP + 2'-deoxyguanosine
GDP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
GTP + 2'-deoxyinosine
GDP + 2'-deoxyinosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
GTP + deoxyguanosine
GDP + dGMP
show the reaction diagram
-
50% of activity with ATP
-
?
triphosphate + 2'-deoxyguanosine
diphosphate + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
triphosphate is active with 2'deoxyguanosine, 50% of the activity with ATP
-
-
?
UTP + 2'-deoxyadenosine
UDP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
Q16854
-
-
-
?
UTP + 2'-deoxyadenosine
UDP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
UTP + 2'-deoxyguanosine
UDP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
Q16854
-
-
-
?
UTP + 2'-deoxyguanosine
UDP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
UTP + 2'-deoxyguanosine
UDP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
preferred substrates
-
-
?
UTP + 2'-deoxyinosine
UDP + 2'-deoxyinosine 5'-phosphate
show the reaction diagram
Q16854
-
-
-
?
UTP + 2'-deoxyinosine
UDP + 2'-deoxyinosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
UTP + 9-beta-D-arabinofuranosylguanine
UDP + 9-beta-D-arabinofuranosylguanine 5'-phosphate
show the reaction diagram
-
i.e. nelarabine, activation of the anticancer drug
-
-
?
UTP + deoxyguanosine
UDP + dGMP
show the reaction diagram
-
-
-
?
UTP + deoxyguanosine
UDP + dGMP
show the reaction diagram
-
-
-
?
UTP + deoxyguanosine
UDP + dGMP
show the reaction diagram
-
20% of activity with ATP
-
?
UTP + deoxyguanosine
UDP + dGMP
show the reaction diagram
-
25% of activity with ATP
-
?
GTP + guanosine
GDP + guanosine 5'-phosphate
show the reaction diagram
-
very low activity
-
-
?
additional information
?
-
-
no activity with diphosphate as phosphate donor
-
-
-
additional information
?
-
-
de novo synthesis and salvage of ribonucleotides and deoxyribonucleotides, metabolism overview
-
-
-
additional information
?
-
-
enzyme defect due to genetic alterations leads to tissue-specific mitochondrial DNA depletion causing multi-systemic disease or devastating liver disease
-
-
-
additional information
?
-
-
th enzyme catalyzes the initial phosphorylation of purine deoxynucleosides, enzyme deficiency leads to severe mitochondrial DNA depletion diseases
-
-
-
additional information
?
-
Q16854
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 occurring of nucleoside kinases with strict substrate specificities in other organism, phylogenetic tree, overview
-
-
-
additional information
?
-
-
anticancer drugs 2-chloro-2'-deoxyadenosine, i.e. cladribine, and 2-fluoro-9-beta-D-arabinofuranosyladenine, i.e. clofarabine, are poor substrates
-
-
-
additional information
?
-
-
no activity with several difluorophenyl nucleoside analogues, overview
-
-
-
additional information
?
-
Q16854
substrate interactions, overview, enzyme shows relaxed enantioselectivity, accepting D- and L-enantiomers of beta-deoxyguanosine but with lower activity than alpha-L-deoxyguanosine, and beta-L-deoxyadenosine, enzyme accepts purine deoxynucleosides and analogues as substrates utilizing a triphosphate donor substrate
-
-
-
additional information
?
-
-
substrate specificity, the enzyme utilizes all naturally occurring ribo-and deoxyribonucleosides triphosphates, with the exception of dGTP, as phosphate donors, and shows poor activity with thymidine, inosine, adenosine, 2,3-dideoxyguanosine, 2,3-dideoxyinosine, 2,3-dideoxyadenosine, and hypoxanthine arabinoside as acceptor substrates
-
-
-
additional information
?
-
-
the enzyme is highly specific for purine substrates, Arg118 is responsible for the substrate specificity
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
Q16854
-
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 2'-deoxyadenosine
ADP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
-
key enzyme in mitochondrial DNA precursor 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
-
-
-
-
ir
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
Q16854
-
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
key enzyme in mitochondrial DNA precursor synthesis
-
-
?
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
important enzyme for the phosphorylation/activation of 2'-deoxyguanosine
-
-
ir
ATP + 2'-deoxyguanosine
ADP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
-
one of the two mitochondrial deoxynucleoside salvage pathway enzymes involved in precursor synthesis for mitochondrial DNA replication, DGUOK is responsible for the initial rate-limiting phosphorylation of the purine deoxynucleosides, mutations of the enzyme are associated with the hepato-specific and hepatocerebral forms of the mtDNA depletion syndrome
-
-
?
ATP + 2'-deoxyinosine
ADP + 2'-deoxyinosine 5'-phosphate
show the reaction diagram
Q16854
-
-
-
?
ATP + 2'-deoxyinosine
ADP + 2'-deoxyinosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
enzyme of purine deoxynucleoside salvage pathway
-
?
ATP + deoxyguanosine
ADP + dGMP
show the reaction diagram
-
first reaction in reutilization of deoxyguanosine for dGTP biosynthesis
-
?
ATP + deoxyinosine
ADP + dIMP
show the reaction diagram
-
recombinant mitochondrial deoxyguanosine kinase, may be the preferred substrate in vivo
-
?
UTP + 2'-deoxyadenosine
UDP + 2'-deoxyadenosine 5'-phosphate
show the reaction diagram
Q16854
-
-
-
?
UTP + 2'-deoxyguanosine
UDP + 2'-deoxyguanosine 5'-phosphate
show the reaction diagram
Q16854
-
-
-
?
ATP + dioxolane guanosine
ADP + dioxolane guanosine 5'-phosphate
show the reaction diagram
-
low activity, step in anabolism of amdoxovir, i.e. (-)-beta-D-2,6-diaminopurine dioxolane, a prodrug of dioxolane guanosine
-
-
?
additional information
?
-
-
de novo synthesis and salvage of ribonucleotides and deoxyribonucleotides, metabolism overview
-
-
-
additional information
?
-
-
enzyme defect due to genetic alterations leads to tissue-specific mitochondrial DNA depletion causing multi-systemic disease or devastating liver disease
-
-
-
additional information
?
-
-
th enzyme catalyzes the initial phosphorylation of purine deoxynucleosides, enzyme deficiency leads to severe mitochondrial DNA depletion diseases
-
-
-
additional information
?
-
Q16854
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 occurring of nucleoside kinases with strict substrate specificities in other organism, phylogenetic tree, overview
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2'-deoxyadenosine-3'-fluoro-3'-triphosphate
-
70% of the activity with ATP
-
2'-deoxyadenosine-3'-fluoroara-3'-triphosphate
-
13% of the activity with ATP
-
2'-deoxyadenosine-3'-triphosphate
-
53% of the activity with ATP
-
3'-deoxyadenosine-2'-triphosphate
-
119% of the activity with ATP
-
3'-deoxyadenosine-3'-fluoro-2'-triphosphate
-
25% of the activity with ATP
-
3'-deoxyadenosine-3'-fluoroxylo-2'-triphosphate
-
55% of the activity with ATP
-
ATP
-
preferred phosphate donor substrate, stabilizes the enzyme
ATP
Q16854
binding site structure and interactions, Gln111, Arg118, Met99, and Asp147 are involved, overview
UTP
Q16854
-
UTP
-
preferred phosphate donor in vitro
additional information
-
the enzyme utilizes all naturally occurring ribo-and deoxyribonucleosides triphosphates, with the exception of dGTP, as phosphate donors
-
additional information
-
no activity with diphosphate as phosphate donor
-
additional information
Q16854
enzyme accepts several triphosphate donor substrates with preference for ATP and UTP
-
additional information
-
enzyme can use several phosphate donors, but UTP is preferred in vitro
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ba2+
-
slight activation
Ca2+
-
activation
Ca2+
-
52% of activity with Mg2+; activation
Ca2+
-
67% of activity with Mg2+; activation
Ca2+
-
60% of activity with Mg2+; activation
Cd2+
-
slight activation
Cd2+
-
slight activation
Co2+
-
53% of activity with Mg2+
Co2+
-
59% of activity with Mg2+
Cr2+
-
slight activation
Cu2+
-
25% of activity with Mg2+
Fe2+
-
67% of activity with Mg2+
Fe2+
-
slight activation
Fe2+
-
33% of activity with Mg2+
Mg2+
-
required for activity
Mg2+
-
required for activity
Mg2+
-
required for activity
Mg2+
-
required for activity
Mg2+
-
MgNTP2- is most probably the true phosphate donor; required for activity; required for activity, no inhibition by excess Mg2+, at 5 mM
Mn2+
-
can replace Mg2+ to some extent
Mn2+
-
activation, as effective as Mg2+
Mn2+
-
92% of activity with Mg2+
Ni2+
-
slight activation
Zn2+
-
activation, can replace Mg2+ to some extent
Zn2+
-
28% of activity with Mg2+
Zn2+
-
45% of activity with Mg2+
Mn2+
-
activation, as effective as Mg2+
additional information
-
divalent cations required, not activated by Zn2+
additional information
-
not activated by Cu2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1,2-Cyclohexanedione
-
-
1-alpha-D-arabinofuranosylguanine
-
-
2,3-Butanedione
-
-
2-fluoro-9-beta-D-arabinofuranosyladenine
-
-
8-aza-2'-deoxyguanosine
-
-
8-azadeoxyguanosine
-
-
9-beta-D-arabinofuranosylguanine
-
-
ADP
-
1 mM, 45% inhibition at pH 6.0
ADP
-
-
AMP
-
weak inhibition
arabinoadenosine
-
-
arabinocytidine
-
-
arabinosylguanine
-
-
ATP
-
weak inhibition
carbodiimide
-
-
cladribine
-
-
clofarabine
-
-
CMP
-
weak inhibition
CuSO4
-
-
cytarabine
-
-
dADP
-
1 mM, 49% inhibition at pH 6.0
dAMP
-
-
dATP
-
0.1 mM, 62% inhibition
dATP
-
1 mM, 71% inhibition at pH 6.0
dATP
-
-
dATP
Q16854
feedback inhibition
dCDP
-
-
dCMP
-
weak inhibition
dCTP
-
0.1 mM, 48% inhibition
dCTP
-
-
deoxyadenosine
-
0.07 mM, 9% inhibition
deoxyadenosine
-
weak inhibition
deoxyadenosine
-
-
deoxyinosine
-
0.07 mM, 17% inhibition
deoxyinosine
-
-
deoxyinosine
-
-
dGDP
-
0.1 mM, 97% inhibition
dGDP
-
0.1 mM, 55% inhibition
dGDP
-
0.0021 mM, 50% inhibition, reversed by 0.2 mM dTTP
dGDP
-
-
dGMP
-
-
dGMP
-
very weak inhibition
dGMP
-
0.1 mM, 44% inhibition
dGMP
-
1 mM, 64% inhibition at pH 6.0
dGMP
-
-
dGMP
-
noncompetitive versus UTP and 2'-deoxyguanosine
dGMP
-
-
dGTP
-
0.1 mM, 99% inhibition
dGTP
-
1 mM, 96% inhibition
dGTP
-
0.1 mM, complete inhibition
dGTP
-
0.001 mM, 50% inhibition, 1 mM, complete inhibition, reversed by 0.2 mM dTTP
dGTP
-
-
dGTP
-
-
dGTP
Q74HC2
0.5 mM, 95% of recombinant dGK
dGTP
Q16854
feedback inhibition
dIMP
-
-
dIMP
-
-
diphosphate
-
competitive inhibition
dITP
-
0.1 mM, 65% inhibition
dITP
-
-
dTDP
-
-
dTDP
-
1 mM, 51% inhibition at pH 6.0
dTDP
-
-
dTMP
-
weak inhibition
dTTP
-
0.1 mM, 30% inhibition
dUTP
-
-
EDTA
-
-
Ethoxyformic anhydride
-
deoxyguanosine slightly protects
GDP
-
1 mM, 50% inhibition at pH 6.0
gemcitabine
-
-
GMP
-
weak inhibition
GTP
-
0.1 mM, 33% inhibition
guanosine
-
-
IDP
-
1 mM, 58% inhibition at pH 6.0
N-ethylmaleimide
-
-
p-mercuribenzoate
-
-
ribavirin
-
-
Rose Bengal mediated photooxidation
-
deoxyguanosine protects
-
UDP
-
strong inhibition
UDP
-
competitive versus UTP, noncompetitive versus 2'-deoxyguanosine
UMP
-
0.1 mM, 24% inhibition
UTP
-
0.1 mM, 30% inhibition
UTP
-
substrate inhibition, overview
Iodine
-
-
additional information
-
not inhibited by deoxyadenosine
-
additional information
-
not inhibited by dADP; not inhibited by dATP; not inhibited by dCTP; not inhibited by GTP
-
additional information
-
not inhibited by acyclovir, 6-thiodeoxyguanosine, methylacetimidate, pyridoxal phosphate; not inhibited by deoxyadenosine; not inhibited by deoxycytidine, adenosine; not inhibited by guanosine
-
additional information
-
not inhibited by dAMP
-
additional information
-
not inhibited by deoxycytidine, adenosine; not inhibited by dTTP; not inhibited by inosine, cytidine, uridine, deoxythymidine, deoxyuridine
-
additional information
-
no substrate inhibition by CTP, ATP, and GTP
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
CTP
-
activation, with ATP as substrate at pH 7
dCDP
-
slight stimulation, with ATP as substrate
dTDP
-
1 mM, 620% activation of mitochondrial deoxyguanosine kinase, positive modulation with ATP as substrate
dTTP
-
1 mM, 280% activation of mitochondrial deoxyguanosine kinase
dTTP
-
1 mM, 3-4fold activation of deoxyguanosine kinase at pH 7.0
Sodium diphosphate
-
1 mM, 120% stimulation of mitochondrial deoxyguanosine kinase
Triton X-100
-
maximal activation at concentrations above critical micelle concentration
Triton X-100
Q16854
-
UDP
-
1 mM, 310% activation of mitochondrial deoxyguanosine kinase, with ATP as substrate
UTP
-
1 mM, 190% activation of mitochondrial deoxyguanosine kinase
UTP
-
slight inhibition at pH 6; stimulation with ATP as substrate, at pH 7
dUTP
-
activation, with ATP as substrate, at pH 7
additional information
-
not activated by dCTP or dATP, with ATP as substrate
-
additional information
-
not activated by dTDP
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.019
1-(2-deoxy-beta-D-ribofuranosyl)-7-iodoisocarbostyril
-
pH 7.6, 37C, recombinant enzyme
0.0026
2'-deoxyadenosine
-
patient with double mutation N46S/L266, pH 7.4, 37C
0.0035
2'-deoxyadenosine
-
father (L266R), pH 7.4, 37C
0.0041
2'-deoxyadenosine
-
brother (N46S), pH 7.4, 37C
0.0053
2'-deoxyadenosine
-
mother (N46S), pH 7.4, 37C
0.0068
2'-deoxyadenosine
-
control group, pH 7.4, 37C
0.414
2'-deoxyadenosine
-
pH 7.6, recombinant mutant E227K
0.467
2'-deoxyadenosine
-
pH 7.6, recombinant wild-type enzyme
0.467
2'-deoxyadenosine
-
pH 7.6, wild-type enzyme
0.5
2'-deoxyadenosine
-
pH 7.6, mutant L250S
0.0006
2'-deoxyguanosine
-
pH 8.5, 37C, cosubstrate UTP; pH 8.5, 37C, recombinant enzyme, with UTP as donor substrate
0.0017
2'-deoxyguanosine
-
pH 8.5, 37C, recombinant enzyme, with CTP as donor substrate
0.0017
2'-deoxyguanosine
-
recombinant enzyme, pH 7.6, 37C
0.0018
2'-deoxyguanosine
-
control group, pH 7.4, 37C
0.0019
2'-deoxyguanosine
-
brother (N46S), pH 7.4, 37C
0.002
2'-deoxyguanosine
-
pH 7.6, 37C, recombinant enzyme
0.0023
2'-deoxyguanosine
-
father (L266R), pH 7.4, 37C
0.0028
2'-deoxyguanosine
-
mother (N46S), pH 7.4, 37C
0.0034
2'-deoxyguanosine
-
patient with double mutation N46S/L266, pH 7.4, 37C
0.004
2'-deoxyguanosine
-
pH 7.6, recombinant wild-type enzyme
0.004
2'-deoxyguanosine
-
pH 7.6, wild-type enzyme
0.0052
2'-deoxyguanosine
-
pH 7.6, recombinant mutant E227K
0.0065
2'-deoxyguanosine
-
pH 8.5, 37C, cosubstrate ATP; pH 8.5, 37C, recombinant enzyme, with ATP as donor substrate
0.01
2'-deoxyguanosine
-
pH 8.5, 37C, cosubstrate GTP
0.0104
2'-deoxyguanosine
-
pH 8.5, 37C, recombinant enzyme, with GTP as donor substrate
0.017
2'-deoxyguanosine
-
pH 8.5, 37C, cosubstrate CTP
0.023
2'-deoxyguanosine
-
pH 7.6, mutant L250S
0.123
2'-deoxyguanosine
-
pH 7.6, recombinant mutant R142K
0.056
2-chloro-2'-arabino-fluoro-2'-deoxyadenosine
-
pH 7.6, recombinant mitochondrial deoxyguanosine kinase
0.078
2-chloro-2'-deoxyadenosine
-
pH 7.6, recombinant mitochondrial deoxyguanosine kinase
0.008
2-chlorodeoxyadenosine
-
pH 7.6, 37C, recombinant deoxguanosine kinase, cosubstrate UTP
0.062
2-chlorodeoxyadenosine
-
pH 7.6, 37C, recombinant deoxguanosine kinase, cosubstrate ATP
0.46
2-fluoro-arabinosyl-adenine
-
pH 7.6, recombinant mitochondrial deoxyguanosine kinase
0.033
arabinosyl guanine
-
pH 7.6, recombinant mitochondrial deoxyguanosine kinase
0.0085
ATP
-
pH 7.6, recombinant wild-type enzyme, with 2'-deoxyguanosine
0.0085
ATP
-
pH 7.6, wild-type enzyme, with 2'-deoxyguanosine
0.014
ATP
-
pH 7.6, recombinant mutant E227K, with 2'-deoxyguanosine
0.02
ATP
-
pH 7.5, 37C
0.034
ATP
-
pH 7.6, mutant L250S, with 2'-deoxyguanosine
0.036
ATP
-
pH 8.5, 37C; pH 8.5, 37C, recombinant enzyme, with 2'-deoxyguanosine as acceptor substrate
0.0974
ATP
-
pH 7.6, recombinant mutant R142K, with 2'-deoxyguanosine
0.242
ATP
-
pH 7.6, recombinant mutant E227K, with 2'-deoxyadenosine
0.269
ATP
-
pH 7.6, recombinant wild-type enzyme, with 2'-deoxyadenosine
0.269
ATP
-
pH 7.6, wild-type enzyme, with 2'-deoxyadenosine
0.302
ATP
-
pH 7.6, mutant L250S, with 2'-deoxyadenosine
0.78
ATP
-
pH 7.4, 37C, mitochondrial deoxyguanosine kinase
0.78
ATP
-
-
0.035
CTP
-
pH 8.5, 37C; pH 8.5, 37C, recombinant enzyme, with 2'-deoxyguanosine as acceptor substrate
0.206
deoxyadenosine
Q54UT2
-
0.47
deoxyadenosine
-
pH 7.6, recombinant mitochondrial deoxyguanosine kinase
0.63
deoxyadenosine
-
pH 6.0, 37C
0.34
deoxycytidine
-
pH 7.6, recombinant mitochondrial deoxyguanosine kinase
0.00032
deoxyguanosine
-
pH 8.0, 37C
0.0014
deoxyguanosine
Q54UT2
-
0.0025
deoxyguanosine
-
pH 6.0, 37C
0.0028
deoxyguanosine
-
pH 7.6, 37C, recombinant deoxguanosine kinase, cosubstrate ATP
0.0037
deoxyguanosine
-
pH 7.6, 37C, recombinant deoxguanosine kinase, cosubstrate UTP
0.004
deoxyguanosine
-
pH 7.6, recombinant mitochondrial deoxyguanosine kinase
0.0047
deoxyguanosine
-
pH 7.4, 37C, mitochondrial deoxyguanosine kinase
0.0047
deoxyguanosine
-
-
0.006
deoxyguanosine
-
pH 7.5, 37C, mitochondrial deoxyguanosine kinase
0.007
deoxyguanosine
-
pH 5.2, 37C
0.065
deoxyguanosine
-
pH 8.0, 20C
0.087
deoxyguanosine
-
pH 8.0, 20C
0.34
deoxyguanosine
-
pH 8.0, 20C, D84N mutant enzyme
0.36
deoxyguanosine
-
pH 8.0, 20C, D84A mutant enzyme
0.55
deoxyguanosine
-
pH 8.0, 20C, D84E mutant enzyme
0.76
deoxyguanosine
-
pH 8.0, 20C, R79K mutant enzyme
0.012
deoxyinosine
-
pH 7.6, recombinant mitochondrial deoxyguanosine kinase
0.021
deoxyinosine
-
pH 7.4, 37C, mitochondrial deoxyguanosine kinase
7
dioxolane guanosine
-
recombinant enzyme, pH 7.6, 37C
0.08
dTTP
-
pH 7.4, 37C, mitochondrial deoxyguanosine kinase
0.046
GTP
-
pH 8.5, 37C; pH 8.5, 37C, recombinant enzyme, with 2'-deoxyguanosine as acceptor substrate
0.023
MgATP2-
-
pH 5.2, 37C, at concentrations below 0.5 mM
0.13
MgATP2-
-
pH 6.0, 37C
0.63
MgATP2-
-
pH 5.2, 37C, at concentrations above 0.5 mM
3.3
MgATP2-
-
pH 8.0, 37C
0.092
Triphosphate
-
pH 7.5, 37C
0.006
UTP
-
pH 8.5, 37C; pH 8.5, 37C, recombinant enzyme, with 2'-deoxyguanosine as acceptor substrate
0.125
UTP
-
pH 7.4, 37C, mitochondrial deoxyguanosine kinase
2.2
MgdTTP2-
-
pH 6.0, 37C
additional information
additional information
-
the reaction with triphosphate follows strict Michaelis-Menten kinetics, while ATP exhibits negative cooperativity
-
additional information
additional information
-
reaction of the mutant L250S with 2'-deoxyguanosine follows Michaelis-Menten kinetics, while the reaction with 2'-deoxyadenosine shows biphasic kinetics
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.007
1-(2-deoxy-beta-D-ribofuranosyl)-7-iodoisocarbostyril
-
pH 7.6, 37C, recombinant enzyme
0.03
2'-deoxyguanosine
-
recombinant enzyme, pH 7.6, 37C
0.07
2'-deoxyguanosine
-
pH 7.6, 37C, recombinant enzyme
1.41
2'deoxyguanosine
-
pH 8.5, 37C, recombinant enzyme, with UTP as donor substrate
1.53
2'deoxyguanosine
-
pH 8.5, 37C, recombinant enzyme, with ATP as donor substrate
1.69
2'deoxyguanosine
-
pH 8.5, 37C, recombinant enzyme, with GTP as donor substrate
2.25
2'deoxyguanosine
-
pH 8.5, 37C, recombinant enzyme, with CTP as donor substrate
1.53
ATP
-
pH 8.5, 37C, recombinant enzyme, with 2'-deoxyguanosine as acceptor substrate
2.25
CTP
-
pH 8.5, 37C, recombinant enzyme, with 2'-deoxyguanosine as acceptor substrate
0.0047
deoxyadenosine
Q54UT2
-
1.41
deoxyguanosine
-
pH 8.5, 37C, cosubstrate UTP
1.53
deoxyguanosine
-
pH 8.5, 37C, cosubstrate ATP
1.69
deoxyguanosine
-
pH 8.5, 37C, cosubstrate GTP
2.25
deoxyguanosine
-
pH 8.5, 37C, cosubstrate CTP
3
deoxyguanosine
Q54UT2
-
0.025
dioxolane guanosine
-
recombinant enzyme, pH 7.6, 37C
1.69
GTP
-
pH 8.5, 37C, recombinant enzyme, with 2'-deoxyguanosine as acceptor substrate
1.41
UTP
-
pH 8.5, 37C, recombinant enzyme, with 2'-deoxyguanosine as acceptor substrate
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.117
1-alpha-D-arabinofuranosylguanine
-
pH 7.4, 37C, competitive vs. deoxyguanosine, mitochondrial deoxyguanosine kinase
0.43
8-aza-2'-deoxyguanosine
-
pH 7.4, 37C, competitive vs. deoxyguanosine, mitochondrial deoxyguanosine kinase
1
ADP
-
pH 7.4, 37C, noncompetitive vs. deoxyguanosine, mitochondrial deoxyguanosine kinase
0.028
dAMP
-
pH 7.6, 37C, recombinant deoxyguanosine kinase
0.041
dATP
-
pH 7.6, 37C, recombinant deoxyguanosine kinase
0.34
deoxyadenosine
-
pH 8.0, 37C
0.075
deoxyinosine
-
pH 7.4, 37C, competitive vs. deoxyguanosine, mitochondrial deoxyguanosine kinase
0.00052
dGDP
-
pH 7.4, 37C, vs. ATP, mitochondrial deoxyguanosine kinase
0.0007
dGDP
-
pH 5.2, 37C, competitive vs. MgATP2-, at MgATP2- concentrations above 0.5 mM
0.0087
dGDP
-
pH 7.4, 37C, vs. deoxyguanosine, mitochondrial deoxyguanosine kinase
0.004
dGMP
-
pH 7.6, 37C, recombinant deoxyguanosine kinase
0.0058
dGMP
-
pH 7.4, 37C, vs. ATP mitochondrial deoxyguanosine kinase
0.009
dGMP
-
pH 7.4, 37C, vs. dTTP, mitochondrial deoxyguanosine kinase
0.076
dGMP
-
pH 8.0, 37C
0.1
dGMP
-
pH 7.4, 37C, vs. deoxyguanosine, mitochondrial deoxyguanosine kinase
0.18
dGMP
-
pH 5.2, 37C, competitive vs. deoxyguanosine
0.25
dGMP
-
pH 7.4, 37C, vs.ATP, mitochondrial deoxyguanosine kinase
0.00003
dGTP
-
pH 7.4, 37C, vs. ATP, mitochondrial deoxyguanosine kinase
0.00007
dGTP
-
pH 5.2, 37C, competitive vs. MgATP2-, at MgATP2- concentrations above 0.5 mM
0.0004
dGTP
-
pH 7.6, 37C, recombinant deoxyguanosine kinase
0.00093
dGTP
-
pH 7.4, 37C, vs. deoxyguanosine, mitochondrial deoxyguanosine kinase
0.0019
dGTP
-
pH 5.2, 37C, competitive vs. deoxyguanosine
0.0019
dGTP
-
pH 8.0, 20C, vs. ATP
0.00333
dGTP
-
pH 8.0, 20C, vs. deoxyguanosine
0.021
dGTP
-
pH 8.0, 37C
0.031
dIMP
-
pH 7.4, 37C, vs. ATP, mitochondrial deoxyguanosine kinase
0.078
dIMP
-
pH 7.6, 37C, recombinant deoxyguanosine kinase
0.098
dIMP
-
pH 7.4, 37C, vs. deoxyguanosine, mitochondrial deoxyguanosine kinase
0.0001
dITP
-
pH 7.4, 37C, vs. ATP, mitochondrial deoxyguanosine kinase
0.0026
dITP
-
pH 7.4, 37C, vs. deoxyguanosine, mitochondrial deoxyguanosine kinase
0.21
dTDP
-
pH 7.4, 37C, vs. ATP, mitochondrial deoxyguanosine kinase
0.39
dTDP
-
pH 7.4, 37C, vs. deoxyguanosine, mitochondrial deoxyguanosine kinase
0.003
UDP
-
pH 5.2, 37C, competitive vs. MgATP2-, at MgATP2- concentrations above 0.5 mM
0.063
UDP
-
pH 8.5, 37C, cosubstrate UTP
0.73
dTDP
-
pH 7.4, 37C, vs. dTTP, mitochondrial deoxyguanosine kinase
additional information
additional information
-
product inhibition of the enzyme, overview
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0000032
-
CEM lymphocytes
0.0000338
-
-
0.0000635
-
differentiated adipocytes
0.0007
-
-
0.007
-
purified recombinant enzyme, substrates deoxyguanosine and ATP
0.0103
-
-
0.023
-
substrate 2'-deoxyguanosine and ATP
0.028
-
using 9-beta-D-arabinofuranosylguanine as substrate, in the presence of 1 mM deoxycytidine, in 50 mM Tris-HCl (pH 7.6) containing 5 mM ATP, 4 mM dithiothreitol, 10 mM sodium fluoride and 5 mM MgCl2
0.04 - 0.05
-
recombinant mitochondrial deoxyguanosine kinase
0.058
-
using deoxyguanosine as substrate, in the presence of 1 mM deoxycytidine, in 50 mM Tris-HCl (pH 7.6) containing 5 mM ATP, 4 mM dithiothreitol, 10 mM sodium fluoride and 5 mM MgCl2
0.073
-
using 2-chlorodeoxyadenosine as substrate, in the presence of 1 mM deoxycytidine, in 50 mM Tris-HCl (pH 7.6) containing 5 mM ATP, 4 mM dithiothreitol, 10 mM sodium fluoride and 5 mM MgCl2
0.54
-
enzyme in crude recombinant Escherichia coli cell extract, substrate 2'-deoxyguanosine
2.3
-
dAdo/dCyd kinase in crude recombinant Escherichia coli cell extract, substrate 2'-deoxyadenosine or 2'-deoxycytidine
8.1
-
purified recombinant enzyme, substrate 2'-deoxyguanosine; recombinant deoxyguanosine kinase
additional information
-
catalytic efficiencies of wild-type and muztant enzymes
additional information
-
catalytic efficiencies, wild-type and mutant enzymes
additional information
-
catalytic efficiencies of the purified recombinant enzyme
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.2
-
substrate deoxyguanosine
5.5
-
-
6
-
cosubstrate ATP
6.8
-
cosubstrate ATP, addition of dTTP
7
-
cosubstrate dTTP
7.4
-
cosubstrates dTTP or UTP
7.5
-
assay at
8.5
-
-
9
-
; broad optimum
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.5 - 9
-
approx. 20% of maximal activity at pH 4.5 and pH 6.5 respectively, approx. 10% of maximal activity at pH 9.0
5 - 9
-
approx. 55% of maximal activity at pH 5.5 and pH 9, plateau with approx. 85% of maximal activity at pH 6.0-7.5
5
-
rapid decrease of activity below
5.6 - 9
-
more than 80% of maximal activity at pH 7.5 and pH 11.5, respectively, 60% of maximal activity at pH 6.0, complete loss of activity below pH 5.6
6 - 11.5
-
over 80% of maximal activity at pH 7.5 and pH 11.5, about 60% of maximal activity at pH 6.0, enzyme is completely inactive below pH 5.6
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37 - 40
-
-
37
-
assay at
37
-
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30 - 53
-
17% loss of activity at 53C, 50% loss of activity at 30C and 53C
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.9
-
mitochondrial deoxyguanosine kinase, isoelectric focusing
5.9
-
-
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
Q9QX60
low expression levels
Manually annotated by BRENDA team
-
3fold increase when cells start to proliferate
Manually annotated by BRENDA team
-
proliferating lymphocyte
Manually annotated by BRENDA team
-
human epithelial kidney 293 cells
Manually annotated by BRENDA team
-
from forearm skin
Manually annotated by BRENDA team
-
genotyping of the enzyme splicing variants and mutants in fibroblast cell lines
Manually annotated by BRENDA team
-
3fold increase when cells start to proliferate
Manually annotated by BRENDA team
-
no increase in activity when cells proliferate
Manually annotated by BRENDA team
-
human epithelial kidney 293 cells
Manually annotated by BRENDA team
Q9QX60
low expression
Manually annotated by BRENDA team
-
acute T lymphoblastic leukemia molt-4 cells
Manually annotated by BRENDA team
-
cell lines PanC-1 and MIA PaCa-2
Manually annotated by BRENDA team
-
neonatal skin tissue
Manually annotated by BRENDA team
Q9QX60
high expression levels
Manually annotated by BRENDA team
Q9QX60
high expression, high expression levels
Manually annotated by BRENDA team
-
3fold increase when cells start to proliferate
Manually annotated by BRENDA team
additional information
-
enzyme is expressed in most tissues, enzyme expression throughout the cell cycle
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Q9QX60
deoxyguanosine kinase 2
Manually annotated by BRENDA team
-
membrane associated
Manually annotated by BRENDA team
-
mitochondrial deoxguanosine kinase is redistributed to the cytosol during apoptosis
Manually annotated by BRENDA team
Q16854
enzyme possesses an N-terminal mitochondrial import signal
Manually annotated by BRENDA team
-
N-terminal enzyme sequence contains a mitochondrial import signal
Manually annotated by BRENDA team
-
deoxyguanosine kinase is encoded by the nuclear DNA and transported into the mitochondria
Manually annotated by BRENDA team
additional information
Q16854
the enzyme leaks out into the cytosol during cell apoptosis
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30000
Q54UT2
SDS-PAGE
675444
44000
-
glycerol density gradient centrifugation
640549
49000
-
recombinant deoxyguanosine kinase, gel filtration; recombinant enzyme, gel filtration
640561
56000
-
mitochondrial deoxyguanosine kinase, equilibrium sedimentation centrifugation
640551
58000
-
gel filtration
640553
58500
-
gel filtration
640552
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
Q16854
2 * 30000
dimer
-
2 * 28000, mitochondrial deoxyguanosine kinase, SDS-PAGE
dimer
-
2 * 29000, second mayor band at 35000 Da, SDS-PAGE
dimer
-
2 * 24147, electrospray mass spectrometry
dimer
-
2 * 27200, heterodimeric dAK/dGK complex, SDS-PAGE
dimer
-
2 * 24147, recombinant enzyme, electrospray mass spectrometry
dimer
Lactobacillus acidophilus R-26
-
2 * 27200, heterodimeric dAK/dGK complex, SDS-PAGE
-
additional information
Q16854
ternary and quarternary structure analysis, overview
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
enzyme in complex with ATP
Q16854
purified recombinant enzyme, hanging drop vapour diffusion method, enzyme solution containing 7 mg/ml protein, 5 mM MgCl2, and 5 mM ATP, mixed with an equal volume of cyrstallization solution containing 0.1 M Na-citrate, pH 6.5, 0.2 M ammonium acetate, and 30% w/v PEG 4000, X-ray diffraction structure determination and analysis at 2.8 A resolution, molecular replacement method
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5
-
95% loss of activity after 30 min at 37C
640551
7
-
most stable
640551
11
-
50% loss of activity after 30 min at 37C
640551
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
-
at least 4 h stable in the presence of Triton X-100, t1/2: 30 min at pH 11, inactivation within 30 min at pH 5.5
640551
40
-
denaturation above 40C, mitochondrial deoxyguanosine kinase
640551
additional information
-
Triton X-100, 0.02%, stabilizes markedly against thermal inactivation
640551
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
bovine serum albumin stabilizes the enzyme in solution
-
highly unstable at 0C in diluted form, no loss of activity in the presence of bovine serum albumin
-
Triton X-100, 0.02%, stabilizes markedly against thermal inactivation
-
ATP stabilizes the enzyme
-
complete inactivation after freezing at -20C or -70C
-
loss of activity in dilute solution
-
Triton X-100 and ATP stabilize
Q16854
ATP or MgATP2- stabilize, not Mg2+ alone
-
loss of activity in dilute solution
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, more than 1 mg/ml protein, 50% glycerol, 1 year, no loss of activity
-
-20C, purified recombinant enzyme at 1 mg/ml, Tris-HCl, pH 7.8, 50% v/v glycerol, at least 1 year without loss of activity
-
0C, the diluted enzyme is highly unstable, but in presence of 1 mg/ml bovine serum albumin, the diluted enzyme is stable for months
-
-80C, stable for at least 1 year
-
4C, 1 week, 50% loss of activity
-
-20C, ammonium sulfate precipitate in 100 mM M Tris-acetate buffer, pH 8, 0.025 M 2-mercaptoethanol, at least 4 months
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant deoxyguanosine kinase, BlueA dye affinity, phenyl-Sepharose; recombinant enzyme from Escherichia coli by affinity and phenyl resin chromatography to homogeneity
-
mitochondrial deoxyguanosine kinase, one-step purification via deoxyguanosine-3'-(4-aminophenylphosphate)-Sepharose affinity chromatography
-
mitochondrial deoxyguanosine kinase, Sephacryl S-200, Blue Sepharose CL6B
-
ammonium sulfate, affinity chromatography on AMP-Sepharose and Blue-Sepharose, DEAE-cellulose, Sephadex G-75
-
enzyme activity is stabilized during purification in presence of Triton X-100 and ATP
Q16854
recombinant enzyme, metal affinity chromatography
-
pH 5.7, streptomycin sulfate, ammonium sulfate
-
pH 5.5, ammonium sulfate, DEAE-Sephadex
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli; gene yaaG of the yaaG/yaaF operon, DNA and amino acid sequence determination and analysis, overexpression in Escherichia coli
-
expression in Escherichia coli
-
expression of wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
-
expression of wild-type and mutant L250S enzymes in Escherichia coli with similar expression levels, the mutant enzyme is poorly soluble
-
expresssion of mitochondrial deoxyguanosine kinase-green fluorescent protein fusion in pancreatic cancer cells
-
gene is localized on chromosome 2q13
Q16854
genetic organization, located on chromosome 2p13, expression as GFP-fusion protein in CHO cells
-
quantitative real-time-PCR
-
expression of dAK/dGK in Escherichia coli
Q74HC2
expression of His-tagged deoxyguanosine kinase in Escherichia coli
Q9QX60
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A2S
-
resulting from a base change G to T at position 4, a G base change immediately after the start codon is likely to affect start codon recognition by the ribosome the patient has an additional base change G to A at position 591 results in skipping of exon 4, very low residual activity
D255Y/D255Y
-
the mutation is associated with deoxyguanosine kinase deficiency
E165V
-
naturally occuring enzyme mutation involved in mitochondrial depletion syndrome
E227K
-
site-directed mutagenesis, mutation is naturally found in patients, unaltered Km but very low Vmax for all substrates compared to the wild-type enzyme
F256X
-
naturally occuring enzyme mutation involved in mitochondrial depletion syndrome
H226R
-
the mutation is associated with a clinical phenotype that consists of neonatal liver failure, nystagmus and hypotonia
K51Q
-
the p.K51Q alteration changes the basic amino acid lysine to the uncharged polar amino acid glutamine in the ATP binding site and is expected to interfere with enzymatic function, the mutation is associated with a clinical phenotype that consists of neonatal liver failure, nystagmus and hypotonia
L250S
-
naturally occurring mutation in a patient with mitochondrial DNA depletion syndrome, patient shows rapidly progressing, early onset fatal liver failure associated with profoundly decreased mtDNA levels in liver and, to a lesser extent, in skeletal muscle, mutation is introduced into the enzyme cDNA via site-directed mutagenesis, the mutant enzyme shows 0.5% remaining activity compared to the wild-type enzyme
L250S/M1T
-
the mutation is associated with deoxyguanosine kinase deficiency
L266R
-
10% residual activity, father of patient with double mutant, 42 of the mean control value for 2'-deoxyguanosine, and 41 of the mean control value for 2'-deoxyadenosine
M1I
-
naturally occuring enzyme mutation involved in mitochondrial depletion syndrome
N46S
-
14% residual activity, mother and brother of patient with double mutant, 61 and 45% of the mean control value for 2'-deoxyguanosine, and 59 and 44% of the mean control value for 2'-deoxyadenosine
N46S
-
the mutation is associated with a clinical phenotype that consists of neonatal liver failure, nystagmus and hypotonia
N46S/L266R
-
naturally occuring mutation, 14 and 10% residual activity as compared with controls with deoxyguanosine and deoxyadenosine, patient shows improved liver tests starting from age 46 month, at age 10 years clinically healthy
N46S/L266R
-
the mutation is associated with deoxyguanosine kinase deficiency
R118C
-
the mutation is associated with a clinical phenotype that consists of neonatal liver failure, nystagmus and hypotonia
R142K
-
site-directed mutagenesis, mutation is naturally found in patients, low activity with dG, no activity with dA compared to the wild-type enzyme
R142K/E227K
-
the mutation is associated with deoxyguanosine kinase deficiency
S52F/S52F
-
the mutation is associated with deoxyguanosine kinase deficiency
W178X
-
the mutation is associated with a clinical phenotype that consists of neonatal liver failure, nystagmus and hypotonia
W65X
-
the mutation is associated with a clinical phenotype that consists of neonatal liver failure, nystagmus and hypotonia
Y191C
-
the mutation is associated with a clinical phenotype that consists of neonatal liver failure, nystagmus and hypotonia
D78A
-
no deoxyguanosine kinase activity
D78E
-
no deoxyguanosine kinase activity
D78N
-
no deoxyguanosine kinase activity
D84A
-
1% of wild-type activity
D84E
-
41% of wild-type activity, not inhibited by dGTP and dATP
D84N
-
5% of wild-type activity
R79k
-
50% of wild-type deoxyguanosine kinase activity
D84A
Lactobacillus acidophilus R-26
-
1% of wild-type activity
-
D84E
Lactobacillus acidophilus R-26
-
41% of wild-type activity, not inhibited by dGTP and dATP
-
D84N
Lactobacillus acidophilus R-26
-
5% of wild-type activity
-
M1V/M1I
-
the mutation is associated with deoxyguanosine kinase deficiency
additional information
-
C-terminally truncated mutants are catalytically inactive, naturally occuring genetic defects/mutations, overview
additional information
-
duplication of bases 763 to 766 in exon 6 results in a truncated non-functional protein, very low residual activity
additional information
-
frame shift mutation c.80delC causes a truncated polypeptide of 64 amino acids and frame shift mutation c763_c766dupGATT results in a truncated polypeptide of 256 amino acids, the c.591G>A nucleotide substitution, located at the end of exon 4 does not result in amino acid change (p.Q197Q), but it changes the consensus splice site sequence, this is predicted to result in aberrant splicing, the frame shift mutation c.605_c.606delGA produces a premature stop codon and a truncated protein of 214 amino acids
additional information
-
identification of deoxyguanosine kinase gene mutations. Most frequent mutation identified in patients with liver pathology is the c.3G>A substitution in the DGUOK exon 1, potentially causing a severe impairment in the synthesis of the protein, geno-y and phenotypes, overview
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
enzyme is useful in anticancer therapy due to activation of anticancer drugs through phosphorylation
medicine
-
the enzyme activates a number of medically important nucleoside analogues