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PROSITE documentation PDOC00320Methylated-DNA--protein-cysteine methyltransferase active site
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PURL: https://purl.expasy.org/prosite/documentation/PDOC00320
The major mutagenic and carcinogenic effect of methylating agents in DNA is the formation of O6-alkylguanine. The repair of DNA containing O6-alkylated guanine is carried out by the enzyme 6-O-methylguanine-DNA methyltransferase (EC 2.1.1.63) (methylated-DNA--protein-cysteine methyltransferase) (MGMT). The alkyl group at the O-6 position is transferred to a cysteine residue in the enzyme [1]. This is a suicide reaction: the enzyme is irreversibly inactivated and the methylated protein accumulates as a dead-end product. Most, but not all MGMT are also able to repair O-4-methylthymine. MGMT sequences have been obtained from various prokaryotic [2] and eukaryotic sources:
- Escherichia coli and Salmonella typhimurium inducible bifunctional protein ada. The N-terminal part of the ada protein functions as a transcriptional activator of its own gene and of other alkylation repair genes, while the C-terminal part functions as a MGMT.
- Bacillus subtilis adaB. In this bacteria the function of the ada complex is carried out by two proteins: adaA, a transcriptional activator, and adaB, a MGMT.
- Escherichia coli constitutive (non-inducible) Ogt enzyme.
- Bacillus subtilis constitutive (non-inducible) Dat1 enzyme.
- Yeast DNA repair enzyme MGT1.
- Mammalian MGMT protein [3].
In all these enzymes the region around the active site cysteine residue is conserved and can be used as a signature pattern.
Last update:December 1992 / Text revised.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Lindahl T. Sedgwick B. Sekiguchi M. Nakabeppu Y. |
| Title | Regulation and expression of the adaptive response to alkylating agents. | |
| Source | Annu. Rev. Biochem. 57:133-157(1988). | |
| PubMed ID | 3052269 | |
| DOI | 10.1146/annurev.bi.57.070188.001025 |
| 2 | Authors | Samson L. |
| Title | The suicidal DNA repair methyltransferases of microbes. | |
| Source | Mol. Microbiol. 6:825-831(1992). | |
| PubMed ID | 1602962 |
| 3 | Authors | Rafferty J.A. Elder R.H. Watson A.J. Cawkwell L. Potter P.M. Margison G.P. |
| Title | Isolation and partial characterisation of a Chinese hamster O6-alkylguanine-DNA alkyltransferase cDNA. | |
| Source | Nucleic Acids Res. 20:1891-1895(1992). | |
| PubMed ID | 1579490 |
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