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 | 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 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 | 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 | 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 (Comment) | Organism |
---|---|
- |
Homo sapiens |
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 | Comment | Organism |
---|---|---|
MTH1 | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
30 | - |
assay at | Homo sapiens |
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 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 Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
8 | - |
assay at | Homo sapiens |
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 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 |