2kif

Publication Abstract from PubMed

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.

Structural basis of O6-alkylguanine recognition by a bacterial alkyltransferase-like DNA repair protein.,Aramini JM, Tubbs JL, Kanugula S, Rossi P, Ertekin A, Maglaqui M, Hamilton K, Ciccosanti CT, Jiang M, Xiao R, Soong TT, Rost B, Acton TB, Everett JK, Pegg AE, Tainer JA, Montelione GT J Biol Chem. 2010 Apr 30;285(18):13736-41. Epub 2010 Mar 8. PMID:20212037^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.