title: Active site and complete sequence of the suicidal methyltransferase that counters alkylation mutagenesis.
abstract: The inducible resistance to alkylation mutagenesis and killing in Escherichia coli (the adaptive response) is controlled by the ada gene. The Ada protein acts both as a positive regulator of the response and as a DNA repair enzyme, correcting premutagenic O6-alkylguanine in DNA by suicidal transfer of the alkyl group to one of its own cysteine residues. We have determined the DNA sequence of the cloned ada+ gene and its regulatory region. The data reveal potential sites of ada autoregulation. Amino acid sequence determinations show that the active center for the O6-methylguanine-DNA methyltransferase is located close to the polypeptide COOH terminus and has the unusual sequence -Pro-Cys-His-, preceded by a very hydrophobic region. These same structural features are present at the active site of thymidylate synthase, suggesting a common chemical mechanism for activation of the cysteine.
mesh_terms: D000478:Alkylation; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D004260:DNA Repair; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D005798:Genes, Bacterial; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D019853:O(6)-Methylguanine-DNA Methyltransferase; D009876:Operon; D013940:Thymidylate Synthase / Q000378:metabolism
chemical_list: D008780:Methyltransferases; D013940:Thymidylate Synthase; D019853:O(6)-Methylguanine-DNA Methyltransferase