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PROSITE documentation PDOC00320

Methylated-DNA--protein-cysteine methyltransferase active site





Description

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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Technical section

PROSITE method (with tools and information) covered by this documentation:

MGMT, PS00374; Methylated-DNA--protein-cysteine methyltransferase active site  (PATTERN)


References

1AuthorsLindahl T. Sedgwick B. Sekiguchi M. Nakabeppu Y.
TitleRegulation and expression of the adaptive response to alkylating agents.
SourceAnnu. Rev. Biochem. 57:133-157(1988).
PubMed ID3052269
DOI10.1146/annurev.bi.57.070188.001025

2AuthorsSamson L.
TitleThe suicidal DNA repair methyltransferases of microbes.
SourceMol. Microbiol. 6:825-831(1992).
PubMed ID1602962

3AuthorsRafferty J.A. Elder R.H. Watson A.J. Cawkwell L. Potter P.M. Margison G.P.
TitleIsolation and partial characterisation of a Chinese hamster O6-alkylguanine-DNA alkyltransferase cDNA.
SourceNucleic Acids Res. 20:1891-1895(1992).
PubMed ID1579490



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