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Literature summary extracted from

  • Sakai, Y.; Furuichi, M.; Takahashi, M.; Mishima, M.; Iwai, S.; Shirakawa, M.; Nakabeppu, Y.
    A molecular basis for the selective recognition of 2-hydroxy-dATP and 8-oxo-dGTP by human MTH1 (2002), J. Biol. Chem., 277, 8579-8587.
    View publication on PubMed

Protein Variants

EC Number Protein Variants Comment Organism
3.6.1.56 D119A mutation completely abolishes the 2-hydroxy-dATP-hydrolyzing ability, whereas the mutant retains substantial levels of 8-oxo-dGTPase activity Homo sapiens
3.6.1.56 D119N mutation completely abolishes the 2-hydroxy-dATP-hydrolyzing ability, whereas the mutant retains substantial levels of 8-oxo-dGTPase activity Homo sapiens
3.6.1.56 L150A mutant enzyme with decrased thermostability. Tm-value is 50°C compared to 65°C for the wild-type enzyme Homo sapiens
3.6.1.56 additional information sequence comparison with the Escherichia coli homolog, MutT, which hydrolyzes only 8-oxo-dGTP and 8-oxo-GTP but not oxidized forms of dATP or ATP. Neither a replacement of the phosphohydrolase module of MTH1 with that of MutT nor deletions of the C-terminal region of MTH1, which is unique for MTH1, alter the substrate specificity of MTH1. In contrast, the substitution of residues at position Trp117 and Asp119 of MTH1, which show apparent chemical shift perturbations with 8-oxo-dGDP in NMR analyses but are not conserved in MutT, affected the substrate specificity. Trp117 is essential for MTH1 to recognize both 8-oxo-dGTP and 2-hydroxy-dATP, whereas Asp119 is only essential for recognizing 2-hydroxy-dATP, thus suggesting that origins of the substrate-binding pockets for MTH1 and MutT are different Homo sapiens
3.6.1.56 V156A mutant enzyme with decrased thermostability. Tm-value is 61°C compared to 65°C for the wild-type enzyme Homo sapiens
3.6.1.56 W117A the specific activities for 2-hydroxy-dATPase and 8-oxo-dGTPase is decreased significantly compared to wild-type activity. About 10% levels of 2-hydroxy-dATPase and 8-oxo-dGTPase activities compared with wild type hMTH1 are detected in the crude extracts, whereas no activity is detected in the purified preparation Homo sapiens
3.6.1.56 W117Y the specific activities for 8-oxo-dGTPase is decreased significantly compared to wild-type activity, 2-hydroxy-dATPase activity exceeds wild type level Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.6.1.56 2-hydroxy-dATP the hydrolysis of 8-oxo-dGTP (0.01 mM) by wild type and F27A decreases to 42% and 44% of the control in the presence of 0.01 mM 2-hydroxy-dATP. 8-oxo-dGTPase activities of D119A and D119N mutants are not altered in the presence of 2-hydroxy-dATP up to 0.1 mM Homo sapiens
3.6.1.56 8-oxo-dGTP the hydrolysis of 2-hydroxy-dATP (0.01 mM) by wild type hMTH1 is inhibited to 50% of the control in the presence of 0.017 mM 8-oxo-dGTP, whereas the W117Y mutant efficiently hydrolyzes 2-hydroxy-dATP even in the presence of 0.1 mM 8-oxodGTP and its initial velocity is 57% of the control Homo sapiens
3.6.1.56 dATP the 8-oxo-dGTPase activity of wild type hMTH1 decreases to 79.6% of the control in the presence of 0.1 mM dATP Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
3.6.1.56 0.0087
-
 2-hydroxy-dATP pH 8.0, 30°C, wild-type enzyme Homo sapiens
3.6.1.56 0.0151
-
 8-oxo-dGTP pH 8.0, 30°C, wild-type enzyme Homo sapiens
3.6.1.56 0.017
-
 2-hydroxy-dATP pH 8.0, 30°C, mutant enzyme F27A Homo sapiens
3.6.1.56 0.0302
-
 8-oxo-dGTP pH 8.0, 30°C, mutant enzyme D119A Homo sapiens
3.6.1.56 0.0403
-
 8-oxo-dGTP pH 8.0, 30°C, mutant enzyme F27A Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
3.6.1.55 8-oxo-dGTP + H2O Escherichia coli 8-oxo-dGTP i.e. 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate 8-oxo-dGMP + diphosphate
-
 ?
3.6.1.56 2-hydroxy-ATP + H2O Homo sapiens 8-oxo-dGTP i.e. 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate. MTH1 hydrolyzes oxidized purine nucleoside triphosphates such as 8-oxo-dGTP, 8-oxo-dATP, 2-hydroxy-dATP, and 2-hydroxy-ATP to monophosphates, and thus avoids errors caused by their misincorporation during DNA replication or transcription, which may result in carcinogenesis or neurodegeneration 2-hydroxy-AMP + diphosphate
-
 ?
3.6.1.56 2-hydroxy-dATP + H2O Homo sapiens 8-oxo-dGTP i.e. 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate. MTH1 hydrolyzes oxidized purine nucleoside triphosphates such as 8-oxo-dGTP, 8-oxo-dATP, 2-hydroxy-dATP, and 2-hydroxy-ATP to monophosphates, and thus avoids errors caused by their misincorporation during DNA replication or transcription, which may result in carcinogenesis or neurodegeneration 2-hydroxy-dAMP + diphosphate
-
 ?
3.6.1.56 8-oxo-dATP + H2O Homo sapiens 8-oxo-dGTP i.e. 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate. MTH1 hydrolyzes oxidized purine nucleoside triphosphates such as 8-oxo-dGTP, 8-oxo-dATP, 2-hydroxy-dATP, and 2-hydroxy-ATP to monophosphates, and thus avoids errors caused by their misincorporation during DNA replication or transcription, which may result in carcinogenesis or neurodegeneration 8-oxo-dAMP + diphosphate
-
 ?
3.6.1.56 8-oxo-dGTP + H2O Homo sapiens 8-oxo-dGTP i.e. 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate. MTH1 hydrolyzes oxidized purine nucleoside triphosphates such as 8-oxo-dGTP, 8-oxo-dATP, 2-hydroxy-dATP, and 2-hydroxy-ATP to monophosphates, and thus avoids errors caused by their misincorporation during DNA replication or transcription, which may result in carcinogenesis or neurodegeneration. This enzyme is a 2-hydroxy-dATP diphosphatase that also exhibits activity with 8-oxo-dGTP 8-oxo-dGMP + diphosphate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
3.6.1.55 Escherichia coli
-
-
-
3.6.1.56 Homo sapiens P36639 sequence comparison with the Escherichia coli homolog, MutT, which hydrolyzes only 8-oxo-dGTP and 8-oxo-GTP but not oxidized forms of dATP or ATP
-

Purification (Commentary)

EC Number Purification (Comment) Organism
3.6.1.56
-
 Homo sapiens

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.6.1.55 8-oxo-dGTP + H2O 8-oxo-dGTP i.e. 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate Escherichia coli 8-oxo-dGMP + diphosphate
-
 ?
3.6.1.55 additional information no hydrolysis of 2-hydroxy-dATP Escherichia coli ?
-
 ?
3.6.1.56 2-hydroxy-ATP + H2O 8-oxo-dGTP i.e. 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate. MTH1 hydrolyzes oxidized purine nucleoside triphosphates such as 8-oxo-dGTP, 8-oxo-dATP, 2-hydroxy-dATP, and 2-hydroxy-ATP to monophosphates, and thus avoids errors caused by their misincorporation during DNA replication or transcription, which may result in carcinogenesis or neurodegeneration Homo sapiens 2-hydroxy-AMP + diphosphate
-
 ?
3.6.1.56 2-hydroxy-dATP + H2O 8-oxo-dGTP i.e. 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate. MTH1 hydrolyzes oxidized purine nucleoside triphosphates such as 8-oxo-dGTP, 8-oxo-dATP, 2-hydroxy-dATP, and 2-hydroxy-ATP to monophosphates, and thus avoids errors caused by their misincorporation during DNA replication or transcription, which may result in carcinogenesis or neurodegeneration Homo sapiens 2-hydroxy-dAMP + diphosphate
-
 ?
3.6.1.56 2-hydroxy-dATP + H2O is more efficiently hydrolyzed to the monophosphate than is 8-oxo-dGTP Homo sapiens 2-hydroxy-dAMP + diphosphate
-
 ?
3.6.1.56 8-oxo-dATP + H2O 8-oxo-dGTP i.e. 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate. MTH1 hydrolyzes oxidized purine nucleoside triphosphates such as 8-oxo-dGTP, 8-oxo-dATP, 2-hydroxy-dATP, and 2-hydroxy-ATP to monophosphates, and thus avoids errors caused by their misincorporation during DNA replication or transcription, which may result in carcinogenesis or neurodegeneration Homo sapiens 8-oxo-dAMP + diphosphate
-
 ?
3.6.1.56 8-oxo-dGTP + H2O 8-oxo-dGTP i.e. 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate. MTH1 hydrolyzes oxidized purine nucleoside triphosphates such as 8-oxo-dGTP, 8-oxo-dATP, 2-hydroxy-dATP, and 2-hydroxy-ATP to monophosphates, and thus avoids errors caused by their misincorporation during DNA replication or transcription, which may result in carcinogenesis or neurodegeneration. This enzyme is a 2-hydroxy-dATP diphosphatase that also exhibits activity with 8-oxo-dGTP Homo sapiens 8-oxo-dGMP + diphosphate
-
 ?
3.6.1.56 8-oxo-dGTP + H2O 8-oxo-dGTP i.e. 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate. This enzyme is a 2-hydroxy-dATP diphosphatase that also exhibits activity with 8-oxo-dGTP. Trp117 is essential for MTH1 to recognize both 8-oxodGTP and 2-hydroxy-dATP, whereas Asp119 is only essential for recognizing 2-hydroxy-dATP, thus suggesting that origins of the substrate-binding pockets for MTH1 and MutT (from Escherichia coli) are different Homo sapiens 8-oxo-dGMP + diphosphate
-
 ?

Synonyms

EC Number Synonyms Comment Organism
3.6.1.55 MuT
-
 Escherichia coli
3.6.1.56 MTH1
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
3.6.1.55 30
-
 assay at Escherichia coli
3.6.1.56 30
-
 assay at Homo sapiens

Temperature Stability [°C]

EC Number Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
3.6.1.56 50
-
 Tm-value for mutant enzyme L150A Homo sapiens
3.6.1.56 55
-
 10 min, wild type hMTH1 retains 94% of the activity in the untreated extracts, mutant enzyme L150A retains 26% of the activity in the untreated extracts Homo sapiens
3.6.1.56 61
-
 Tm-value for mutant enzyme V156A Homo sapiens
3.6.1.56 65
-
 Tm-value for wild-type enzyme. 10 min, wild type hMTH1 retains 49% of the activity in the untreated extracts, mutant enzyme L150A retains 14% of the activity in the untreated extracts Homo sapiens

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
3.6.1.56 9.54
-
 8-oxo-dGTP pH 8.0, 30°C, mutant enzyme D119A Homo sapiens
3.6.1.56 25.1
-
 8-oxo-dGTP pH 8.0, 30°C, mutant enzyme F27A Homo sapiens
3.6.1.56 25.9
-
 8-oxo-dGTP pH 8.0, 30°C, wild-type enzyme Homo sapiens
3.6.1.56 28.7
-
 2-hydroxy-dATP pH 8.0, 30°C, wild-type enzyme Homo sapiens
3.6.1.56 31
-
 2-hydroxy-dATP pH 8.0, 30°C, mutant enzyme F27A Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
3.6.1.55 8
-
 assay at Escherichia coli
3.6.1.56 8
-
 assay at Homo sapiens

General Information

EC Number General Information Comment Organism
3.6.1.56 physiological function MTH1 hydrolyzes oxidized purine nucleoside triphosphates such as 8-oxo-dGTP, 8-oxo-dATP, 2-hydroxydATP, and 2-hydroxy-rATP to monophosphates, and thus avoids errors caused by their misincorporation during DNA replication or transcription, which may result in carcinogenesis or neurodegeneration Homo sapiens

kcat/KM [mM/s]

EC Number kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
3.6.1.56 310
-
 8-oxo-dGTP pH 8.0, 30°C, mutant enzyme D119A Homo sapiens
3.6.1.56 620
-
 8-oxo-dGTP pH 8.0, 30°C, mutant enzyme F27A Homo sapiens
3.6.1.56 1710
-
 8-oxo-dGTP pH 8.0, 30°C, wild-type enzyme Homo sapiens
3.6.1.56 1820
-
 2-hydroxy-dATP pH 8.0, 30°C, mutant enzyme F27A Homo sapiens
3.6.1.56 3300
-
 2-hydroxy-dATP pH 8.0, 30°C, wild-type enzyme Homo sapiens