{PDOC00320} {PS00374; MGMT} {BEGIN} ****************************************************************** * Methylated-DNA--protein-cysteine methyltransferase active site * ****************************************************************** 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. -Consensus pattern: [LIVMF]-P-C-H-R-[LIVMF](2) [C is the active site residue] -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: 2. -Last update: December 1992 / Text revised. [ 1] Lindahl T., Sedgwick B., Sekiguchi M., Nakabeppu Y. "Regulation and expression of the adaptive response to alkylating agents." Annu. Rev. Biochem. 57:133-157(1988). PubMed=3052269; DOI=10.1146/annurev.bi.57.070188.001025 [ 2] Samson L. "The suicidal DNA repair methyltransferases of microbes." Mol. Microbiol. 6:825-831(1992). PubMed=1602962 [ 3] Rafferty J.A., Elder R.H., Watson A.J., Cawkwell L., Potter P.M., Margison G.P. "Isolation and partial characterisation of a Chinese hamster O6-alkylguanine-DNA alkyltransferase cDNA." Nucleic Acids Res. 20:1891-1895(1992). PubMed=1579490 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}