1sfe
From Proteopedia
ADA O6-METHYLGUANINE-DNA METHYLTRANSFERASE FROM ESCHERICHIA COLI
Structural highlights
Function[ADA_ECOLI] Is involved in the adaptive response to alkylation damage in DNA caused by alkylating agents. Repairs O6-methylguanine and 04-methylthymine residues in alkylated DNA by a direct and irreversible transfer of the methyl group from the base to one of its own cysteine residues (Cys-321). Also specifically repairs the Sp diastereomer of DNA methylphosphotriester lesions by the same mechanism, although the methyl transfer occurs onto a different cysteine residue (Cys-38). Can not demethylate the other diastereomer, Rp-methylphosphotriester.[1] The methylation of Ada by methylphosphotriesters in DNA leads to its activation as a transcriptional regulator that activates the transcription of its own gene, ada, and other alkylation resistance genes, alkA, alkB and aidB.[2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe mutagenic and carcinogenic effects of simple alkylating agents are mainly due to methylation at the O6 position of guanine in DNA. O6-methylguanine directs the incorporation of either thymine or cytosine without blocking DNA replication, resulting in GC to AT transition mutations. In prokaryotic and eukaryotic cells antimutagenic repair is effected by direct reversal of this DNA damage. A suicidal methyltransferase repair protein removes the methyl group from DNA to one of its own cysteine residues. The resulting self-methylation of the active site cysteine renders the protein inactive. Here we report the X-ray structure of the 19 kDa C-terminal domain of the Escherichia coli ada gene product, the prototype of these suicidal methyltransferases. In the crystal structure the active site cysteine is buried. We propose a model for the significant conformational change that the protein must undergo in order to bind DNA and effect methyl transfer. Crystal structure of a suicidal DNA repair protein: the Ada O6-methylguanine-DNA methyltransferase from E. coli.,Moore MH, Gulbis JM, Dodson EJ, Demple B, Moody PC EMBO J. 1994 Apr 1;13(7):1495-501. PMID:8156986[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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