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.