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J Biol Chem. 2010 Apr 30;285(18):13736-41. doi: 10.1074/jbc.M109.093591. Epub 2010 Mar 8.

Structural basis of O6-alkylguanine recognition by a bacterial alkyltransferase-like DNA repair protein.

Author information

1
Center for Advanced Biotechnology and Medicine, Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA. jma@cabm.rutgers.edu

Abstract

Alkyltransferase-like proteins (ATLs) are a novel class of DNA repair proteins related to O(6)-alkylguanine-DNA alkyltransferases (AGTs) that tightly bind alkylated DNA and shunt the damaged DNA into the nucleotide excision repair pathway. Here, we present the first structure of a bacterial ATL, from Vibrio parahaemolyticus (vpAtl). We demonstrate that vpAtl adopts an AGT-like fold and that the protein is capable of tightly binding to O(6)-methylguanine-containing DNA and disrupting its repair by human AGT, a hallmark of ATLs. Mutation of highly conserved residues Tyr(23) and Arg(37) demonstrate their critical roles in a conserved mechanism of ATL binding to alkylated DNA. NMR relaxation data reveal a role for conformational plasticity in the guanine-lesion recognition cavity. Our results provide further evidence for the conserved role of ATLs in this primordial mechanism of DNA repair.

PMID:
20212037
PMCID:
PMC2859536
DOI:
10.1074/jbc.M109.093591
[Indexed for MEDLINE]
Free PMC Article

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