EC |
3.6.1.55 |
Accepted name: |
8-oxo-dGTP diphosphatase |
Reaction: |
8-oxo-dGTP + H2O = 8-oxo-dGMP + diphosphate |
Glossary: |
8-oxo-dGTP = 8-oxo-7,8-dihydro-2′-deoxyguanosine 5′-triphosphate |
Other name(s): |
MutT; 7,8-dihydro-8-oxoguanine triphosphatase; 8-oxo-dGTPase; 7,8-dihydro-8-oxo-dGTP pyrophosphohydrolase |
Systematic name: |
8-oxo-dGTP diphosphohydrolase |
Comments: |
This enzyme hydrolyses the phosphoanhydride bond between the α and β phosphate of 8-oxoguanine-containing nucleoside di- and triphosphates thereby preventing misincorporation of the oxidized purine nucleoside triphosphates into DNA. It does not hydrolyse 2-hydroxy-dATP (cf. EC 3.6.1.56, 2-hydroxy-dATP diphosphatase) [4]. Requires Mg2+. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Ito, R., Hayakawa, H., Sekiguchi, M. and Ishibashi, T. Multiple enzyme activities of Escherichia coli MutT protein for sanitization of DNA and RNA precursor pools. Biochemistry 44 (2005) 6670–6674. [DOI] [PMID: 15850400] |
2. |
Yoshimura, K., Ogawa, T., Ueda, Y. and Shigeoka, S. AtNUDX1, an 8-oxo-7,8-dihydro-2′-deoxyguanosine 5′-triphosphate pyrophosphohydrolase, is responsible for eliminating oxidized nucleotides in Arabidopsis. Plant Cell Physiol. 48 (2007) 1438–1449. [DOI] [PMID: 17804481] |
3. |
Nakamura, T., Meshitsuka, S., Kitagawa, S., Abe, N., Yamada, J., Ishino, T., Nakano, H., Tsuzuki, T., Doi, T., Kobayashi, Y., Fujii, S., Sekiguchi, M. and Yamagata, Y. Structural and dynamic features of the MutT protein in the recognition of nucleotides with the mutagenic 8-oxoguanine base. J. Biol. Chem. 285 (2010) 444–452. [DOI] [PMID: 19864691] |
4. |
Yonekura, S., Sanada, U. and Zhang-Akiyama, Q.M. CiMutT, an asidian MutT homologue, has a 7, 8-dihydro-8-oxo-dGTP pyrophosphohydrolase activity responsible for sanitization of oxidized nucleotides in Ciona intestinalis. Genes Genet. Syst. 85 (2010) 287–295. [PMID: 21178309] |
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[EC 3.6.1.55 created 2011] |
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EC |
3.6.1.56 |
Accepted name: |
2-hydroxy-dATP diphosphatase |
Reaction: |
2-hydroxy-dATP + H2O = 2-hydroxy-dAMP + diphosphate |
Other name(s): |
NUDT1; MTH1; MTH2; oxidized purine nucleoside triphosphatase; (2′-deoxy) ribonucleoside 5′-triphosphate pyrophosphohydrolase |
Systematic name: |
2-hydroxy-dATP diphosphohydrolase |
Comments: |
The enzyme hydrolyses oxidized purine nucleoside triphosphates such as 2-hydroxy-dATP, thereby preventing their misincorporation into DNA. It can also recognize 8-oxo-dGTP and 8-oxo-dATP, but with lower efficiency (cf. EC 3.6.1.55, 8-oxo-dGTP diphosphatase) [3]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Sakumi, K., Furuichi, M., Tsuzuki, T., Kakuma, T., Kawabata, S., Maki, H. and Sekiguchi, M. Cloning and expression of cDNA for a human enzyme that hydrolyzes 8-oxo-dGTP, a mutagenic substrate for DNA synthesis. J. Biol. Chem. 268 (1993) 23524–23530. [PMID: 8226881] |
2. |
Kakuma, T., Nishida, J., Tsuzuki, T. and Sekiguchi, M. Mouse MTH1 protein with 8-oxo-7,8-dihydro-2′-deoxyguanosine 5′-triphosphatase activity that prevents transversion mutation. cDNA cloning and tissue distribution. J. Biol. Chem. 270 (1995) 25942–25948. [DOI] [PMID: 7592783] |
3. |
Fujikawa, K., Kamiya, H., Yakushiji, H., Fujii, Y., Nakabeppu, Y. and Kasai, H. The oxidized forms of dATP are substrates for the human MutT homologue, the hMTH1 protein. J. Biol. Chem. 274 (1999) 18201–18205. [DOI] [PMID: 10373420] |
4. |
Sakai, Y., Furuichi, M., Takahashi, M., Mishima, M., Iwai, S., Shirakawa, M. and Nakabeppu, Y. A molecular basis for the selective recognition of 2-hydroxy-dATP and 8-oxo-dGTP by human MTH1. J. Biol. Chem. 277 (2002) 8579–8587. [DOI] [PMID: 11756418] |
5. |
Fujikawa, K., Kamiya, H., Yakushiji, H., Nakabeppu, Y. and Kasai, H. Human MTH1 protein hydrolyzes the oxidized ribonucleotide, 2-hydroxy-ATP. Nucleic Acids Res. 29 (2001) 449–454. [DOI] [PMID: 11139615] |
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[EC 3.6.1.56 created 2011] |
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EC |
3.6.1.58 |
Accepted name: |
8-oxo-dGDP phosphatase |
Reaction: |
(1) 8-oxo-dGDP + H2O = 8-oxo-dGMP + phosphate (2) 8-oxo-GDP + H2O = 8-oxo-GMP + phosphate |
Glossary: |
8-oxo-dGDP = 8-oxo-7,8-dihydro-2′-deoxyguanosine 5′-diphosphate |
Other name(s): |
NUDT5; MTH3 (gene name); NUDT18 |
Systematic name: |
8-oxo-dGDP phosphohydrolase |
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) [4]. The human enzyme NUDT18 also hydrolyses 8-oxo-dADP and 2-hydroxy-dADP, the latter at a slower rate [6]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Ishibashi, T., Hayakawa, H., Ito, R., Miyazawa, M., Yamagata, Y. and Sekiguchi, M. Mammalian enzymes for preventing transcriptional errors caused by oxidative damage. Nucleic Acids Res. 33 (2005) 3779–3784. [DOI] [PMID: 16002790] |
2. |
Ishibashi, T., Hayakawa, H. and Sekiguchi, M. A novel mechanism for preventing mutations caused by oxidation of guanine nucleotides. EMBO Rep. 4 (2003) 479–483. [DOI] [PMID: 12717453] |
3. |
Kamiya, H., Hori, M., Arimori, T., Sekiguchi, M., Yamagata, Y. and Harashima, H. NUDT5 hydrolyzes oxidized deoxyribonucleoside diphosphates with broad substrate specificity. DNA Repair (Amst) 8 (2009) 1250–1254. [DOI] [PMID: 19699693] |
4. |
Ito, R., Sekiguchi, M., Setoyama, D., Nakatsu, Y., Yamagata, Y. and Hayakawa, H. Cleavage of oxidized guanine nucleotide and ADP sugar by human NUDT5 protein. J. Biochem. 149 (2011) 731–738. [DOI] [PMID: 21389046] |
5. |
Zha, M., Zhong, C., Peng, Y., Hu, H. and Ding, J. Crystal structures of human NUDT5 reveal insights into the structural basis of the substrate specificity. J. Mol. Biol. 364 (2006) 1021–1033. [DOI] [PMID: 17052728] |
6. |
Takagi, Y., Setoyama, D., Ito, R., Kamiya, H., Yamagata, Y. and Sekiguchi, M. Human MTH3 (NUDT18) protein hydrolyzes oxidized forms of guanosine and deoxyguanosine diphosphates: comparison with MTH1 and MTH2. J. Biol. Chem. 287 (2012) 21541–21549. [DOI] [PMID: 22556419] |
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[EC 3.6.1.58 created 2012] |
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EC |
3.6.1.69 |
Accepted name: |
8-oxo-(d)GTP phosphatase |
Reaction: |
(1) 8-oxo-GTP + H2O = 8-oxo-GDP + phosphate (2) 8-oxo-dGTP + H2O = 8-oxo-dGDP + phosphate |
Glossary: |
8-oxo-dGTP = 2′-deoxy-7,8-dihydro-8-oxoguanosine 5′-triphosphate |
Other name(s): |
mutT1 (gene name) |
Systematic name: |
8-oxo-dGTP diphosphohydrolase |
Comments: |
The enzyme, characterized from the bacterium Mycobacterium tuberculosis, catalyses the hydrolysis of both 8-oxo-GTP and 8-oxo-dGTP, thereby preventing transcriptional and translational errors caused by oxidative damage. The enzyme is highly specific. Unlike EC 3.6.1.55, 8-oxo-dGTP diphosphatase, it removes only a single phosphate group. The nucleoside diphosphate products are hydrolysed further by EC 3.6.1.58, 8-oxo-dGDP phosphatase. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Patil, A.G., Sang, P.B., Govindan, A. and Varshney, U. Mycobacterium tuberculosis MutT1 (Rv2985) and ADPRase (Rv1700) proteins constitute a two-stage mechanism of 8-oxo-dGTP and 8-oxo-GTP detoxification and adenosine to cytidine mutation avoidance. J. Biol. Chem. 288 (2013) 11252–11262. [PMID: 23463507] |
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[EC 3.6.1.69 created 2019] |
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