Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 3.6.1.56 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

Protein Variants Comment Organism
D119A mutation completely abolishes the 2-hydroxy-dATP-hydrolyzing ability, whereas the mutant retains substantial levels of 8-oxo-dGTPase activity Homo sapiens
D119N mutation completely abolishes the 2-hydroxy-dATP-hydrolyzing ability, whereas the mutant retains substantial levels of 8-oxo-dGTPase activity Homo sapiens
L150A mutant enzyme with decrased thermostability. Tm-value is 50°C compared to 65°C for the wild-type enzyme Homo sapiens
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
V156A mutant enzyme with decrased thermostability. Tm-value is 61°C compared to 65°C for the wild-type enzyme Homo sapiens
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
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

Inhibitors Comment Organism Structure
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
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
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]

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

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
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
-
?
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
-
?
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
-
?
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

Organism UniProt Comment Textmining
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)

Purification (Comment) Organism
-
Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
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
-
?
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
-
?
2-hydroxy-dATP + H2O is more efficiently hydrolyzed to the monophosphate than is 8-oxo-dGTP Homo sapiens 2-hydroxy-dAMP + diphosphate
-
?
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
-
?
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
-
?
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

Synonyms Comment Organism
MTH1
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
30
-
assay at Homo sapiens

Temperature Stability [°C]

Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
50
-
Tm-value for mutant enzyme L150A Homo sapiens
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
61
-
Tm-value for mutant enzyme V156A Homo sapiens
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]

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

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8
-
assay at Homo sapiens

General Information

General Information Comment Organism
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]

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