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PMID: 3887409 Published · ppublish English Journal Article

Active site and complete sequence of the suicidal methyltransferase that counters alkylation mutagenesis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 82 ·No. 9 ·1985-05-00 ·Pages 2688-92

Demple B, Sedgwick B, Robins P, Totty N, Waterfield MD, Lindahl T

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
Alkylation Amino Acid Sequence Base Sequence Binding Sites DNA Repair Escherichia coli/genetics,metabolism Genes, Bacterial Methyltransferases/genetics,metabolism Mutation O(6)-Methylguanine-DNA Methyltransferase Operon Thymidylate Synthase/metabolism
Chemicals
Methyltransferases Thymidylate Synthase O(6)-Methylguanine-DNA Methyltransferase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Demple B
Sedgwick B
Robins P
Totty N
Waterfield M D
Lindahl T
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41 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.82.9.2688
Published
1985-05-00
Pages
2688-92
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC397630
Subset
IM
Databases
GENBANK
M10315
External Links
PubMed source DOI: 10.1073/pnas.82.9.2688 PMC Full Text View journal details
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