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Title | Structural basis of O6-alkylguanine recognition by a bacterial alkyltransferase-like DNA repair protein. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Aramini, JM, Tubbs, JL, Kanugula, S, Rossi, P, Ertekin, A, Maglaqui, M, Hamilton, K, Ciccosanti, CT, Jiang, M, Xiao, R, Soong, T-T, Rost, B, Acton, TB, Everett, JK, Pegg, AE, Tainer, JA, Montelione, GT |
Journal | J Biol Chem |
Volume | 285 |
Issue | 18 |
Pagination | 13736-41 |
Date Published | 2010 Apr 30 |
ISSN | 1083-351X |
Keywords | Alkyl and Aryl Transferases, Amino Acid Substitution, DNA, DNA Repair, Guanine, Humans, Mutation, Missense, Protein Folding, Vibrio parahaemolyticus |
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. |
DOI | 10.1074/jbc.M109.093591 |
Alternate Journal | J. Biol. Chem. |
PubMed ID | 20212037 |
PubMed Central ID | PMC2859536 |
Grant List | CA018137 / CA / NCI NIH HHS / United States CA097209 / CA / NCI NIH HHS / United States R01 CA018137-35 / CA / NCI NIH HHS / United States R01 CA018137-36 / CA / NCI NIH HHS / United States U54-GM074958 / GM / NIGMS NIH HHS / United States |