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Information on EC 3.6.1.58 - 8-oxo-dGDP phosphatase and Organism(s) Homo sapiens and UniProt Accession Q9UKK9

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EC Tree
     3 Hydrolases
         3.6 Acting on acid anhydrides
             3.6.1 In phosphorus-containing anhydrides
                3.6.1.58 8-oxo-dGDP phosphatase
IUBMB Comments
The enzyme catalyses the hydrolysis of both 8-oxo-dGDP and 8-oxo-GDP thereby preventing translational errors caused by oxidative damage. The preferred in vivo substrate is not known. The enzyme does not degrade 8-oxo-dGTP and 8-oxo-GTP to the monophosphates (cf. EC 3.6.1.55, 8-oxo-dGTP diphosphatase) [1,2]. Ribonucleotide diphosphates and deoxyribonucleotide diphosphates are hydrolysed with broad specificity. The bifunctional enzyme NUDT5 also hydrolyses ADP-ribose to AMP and D-ribose 5-phosphate (cf. EC 3.6.1.13, ADP-ribose diphosphatase) . The human enzyme NUDT18 also hydrolyses 8-oxo-dADP and 2-hydroxy-dADP, the latter at a slower rate .
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Homo sapiens
UNIPROT: Q9UKK9
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The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Reaction Schemes
hide
8-oxo-dGDP
+
H2O
=
8-oxo-dGMP
+
phosphate
+
=
+
Synonyms
ndx-1, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
MTH3
-
-
MutT homologue 3
-
-
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
8-oxo-dGDP phosphohydrolase
The enzyme catalyses the hydrolysis of both 8-oxo-dGDP and 8-oxo-GDP thereby preventing translational errors caused by oxidative damage. The preferred in vivo substrate is not known. The enzyme does not degrade 8-oxo-dGTP and 8-oxo-GTP to the monophosphates (cf. EC 3.6.1.55, 8-oxo-dGTP diphosphatase) [1,2]. Ribonucleotide diphosphates and deoxyribonucleotide diphosphates are hydrolysed with broad specificity. The bifunctional enzyme NUDT5 also hydrolyses ADP-ribose to AMP and D-ribose 5-phosphate (cf. EC 3.6.1.13, ADP-ribose diphosphatase) [4]. The human enzyme NUDT18 also hydrolyses 8-oxo-dADP and 2-hydroxy-dADP, the latter at a slower rate [6].
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-hydroxy-dADP + H2O
2-hydroxy-dAMP + phosphate
show the reaction diagram
kcat/KM is 15% of the wild-type value
-
-
?
5-formyl-dUDP + H2O
5-formyl-dUMP + phosphate
show the reaction diagram
kcat/KM is 30% of the wild-type value
-
-
?
8-oxo-dADP + H2O
8-oxo-dAMP + phosphate
show the reaction diagram
8-oxo-dADP is hydrolyzed slightly more efficiently than 8-oxo-dGDP
-
-
?
8-oxo-dGDP + H2O
8-oxo-dGMP + phosphate
show the reaction diagram
dADP + H2O
dAMP + phosphate
show the reaction diagram
kcat/KM is 16% of the wild-type value
-
-
?
dGDP + H2O
dGMP + phosphate
show the reaction diagram
2-hydroxy-dADP + H2O
2-hydroxy-dAMP + phosphate
show the reaction diagram
-
-
-
-
?
8-hydroxy-dADP + H2O
8-hydroxy-dAMP + phosphate
show the reaction diagram
-
-
-
-
?
8-oxo-dGDP + H2O
8-oxo-dGMP + phosphate
show the reaction diagram
8-oxo-dGTP + H2O
8-oxo-dGDP + phosphate
show the reaction diagram
-
the enzyme hardly cleaves 8-oxo-dGTP
-
-
?
8-oxo-GDP + H2O
8-oxo-GMP + phosphate
show the reaction diagram
GDP + H2O
GMP + phosphate
show the reaction diagram
-
Vmax/Km is 6.5% of the value for 8-oxo-GDP
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
8-oxo-dGDP + H2O
8-oxo-dGMP + phosphate
show the reaction diagram
NUDT5 might have a much greater role than MTH1 in preventing the occurrence of mutations that are caused by the misincorporation of 8-oxoguanine in human cells. NUDT5 has another role in promoting the MTH1 reaction, in removing its inhibitor, 8-oxo-dGDP
-
-
?
8-oxo-GDP + H2O
8-oxo-GMP + phosphate
show the reaction diagram
-
-
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
8-oxo-dGDP
-
inhibits cleavage of ADP-ribose
ADP-ribose
-
inhibits cleavage of 8-oxo-dGTP
AMP
-
inhibits cleavage of 8-oxo-dGTP
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0088
2-hydroxy-dADP
pH 8.0, 30°C
0.004
5-formyl-dUDP
pH 8.0, 30°C
0.0029
8-oxo-dADP
pH 8.0, 30°C
0.0021 - 0.77
8-oxo-dGDP
0.0126
dADP
pH 8.0, 30°C
0.0076 - 7.1
dGDP
0.0035 - 0.0107
8-oxo-dGDP
0.0049 - 0.0117
8-oxo-GDP
0.048
GDP
-
pH 8.0, 30°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.004
2-hydroxy-dADP
pH 8.0, 30°C
0.0035
5-formyl-dUDP
pH 8.0, 30°C
0.009
8-oxo-dADP
pH 8.0, 30°C
0.006
8-oxo-dGDP
pH 8.0, 30°C
0.006
dADP
pH 8.0, 30°C
0.015
dGDP
pH 8.0, 30°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.45
2-hydroxy-dADP
pH 8.0, 30°C
0.88
5-formyl-dUDP
pH 8.0, 30°C
3.1
8-oxo-dADP
pH 8.0, 30°C
2.9
8-oxo-dGDP
pH 8.0, 30°C
0.48
dADP
pH 8.0, 30°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
10
-
cleavage of 8-oxo-dGDP
8
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
9.5 - 12
-
pH 9.5: about 50% of maximal activity, pH 12.0: about 50% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
the knockdown of the MTH1, MTH2, and NUDT5 proteins increases the A:T to C:G substitution mutations induced by 8-hydroxy-dGTP. In addition, the increase in the induced mutation frequency is more evident in the triple-knockdown cells
physiological function
physiological function
-
is produced in cells by reactive oxygen species normally formed during cellular metabolic processes. This oxidized base can pair with both adenine and cytosine, and thus the existence of this base in messenger RNA would cause translational errors. The elimination of 8-oxoguanine-containing ribonucleotides from the precursor pool is important to ensure accurate protein synthesis. Both NUDT5 and MTH1 are involved in this process in human cells
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
NUDT5_HUMAN
219
0
24328
Swiss-Prot
other Location (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystals of full-length hNUDT5 are grown at 4°C using the hanging-drop vapor diffusion method. Crystal structures of hNUDT5 in apo form, in complex with ADP-ribose, and in complex with AMP with bound Mg2+
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
HisTrap column chromatography, HiTrap heparin column chromatography, and Mono S column chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
when NUDT5 is expressed in Escherichia coli mutT-cells as a His-tagged protein, the increased frequency of spontaneous mutations is decreased to normal levels
expressed in Escherichia coli BL21 cells
-
the increase in the production of erroneous proteins by oxidative damage is 28fold over the wild-type cells in Escherichia coli mutT deficient cells. By the expression of NUDT5 in the cells, it is reduced to 1.4fold
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kamiya, H.; Hori, M.; Arimori, T.; Sekiguchi, M.; Yamagata, Y.; Harashima, H.
NUDT5 hydrolyzes oxidized deoxyribonucleoside diphosphates with broad substrate specificity
DNA Repair
8
1250-1254
2009
Homo sapiens (Q9UKK9)
Manually annotated by BRENDA team
Ishibashi, T.; Hayakawa, H.; Sekiguchi, M.
A novel mechanism for preventing mutations caused by oxidation of guanine nucleotides
EMBO Rep.
4
479-483
2003
Homo sapiens (Q9UKK9)
Manually annotated by BRENDA team
Hori, M.; Satou, K.; Harashima, H.; Kamiya, H.
Suppression of mutagenesis by 8-hydroxy-2'-deoxyguanosine 5'-triphosphate (7,8-dihydro-8-oxo-2'-deoxyguanosine 5'-triphosphate) by human MTH1, MTH2, and NUDT5
Free Radic. Biol. Med.
48
1197-1201
2010
Homo sapiens (Q9UKK9)
Manually annotated by BRENDA team
Ito, R.; Sekiguchi, M.; Setoyama, D.; Nakatsu, Y.; Yamagata, Y.; Hayakawa, H.
Cleavage of oxidized guanine nucleotide and ADP sugar by human NUDT5 protein
J. Biochem.
149
731-738
2011
Homo sapiens
Manually annotated by BRENDA team
Zha, M.; Zhong, C.; Peng, Y.; Hu, H.; Ding, J.
Crystal structures of human NUDT5 reveal insights into the structural basis of the substrate specificity
J. Mol. Biol.
364
1021-1033
2006
Homo sapiens (Q9UKK9)
Manually annotated by BRENDA team
Ishibashi, T.; Hayakawa, H.; Ito, R.; Miyazawa, M.; Yamagata, Y.; Sekiguchi, M.
Mammalian enzymes for preventing transcriptional errors caused by oxidative damage
Nucleic Acids Res.
33
3779-3784
2005
Homo sapiens
Manually annotated by BRENDA team
Takagi, Y.; Setoyama, D.; Ito, R.; Kamiya, H.; Yamagata, Y.; Sekiguchi, M.
Human MTH3 (NUDT18) protein hydrolyzes oxidized forms of guanosine and deoxyguanosine diphosphates: comparison with MTH1 and MTH2
J. Biol. Chem.
287
21541-21549
2012
Homo sapiens
Manually annotated by BRENDA team