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

James M. Aramini, Julie L. Tubbs, Sreenivas Kanugula, Paolo Rossi, Asli Ertekin, Melissa Maglaqui, Keith Hamilton, Colleen T. Ciccosanti, Mei Jiang, Rong Xiao, Ta Tsen Soong, Burkhard Rost, Thomas B. Acton, John K. Everett, Anthony E. Pegg, John A. Tainer, Gaetano T. Montelione

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Alkyltransferase-like proteins (ATLs) are a novel class of DNA repair proteins related to O6-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 Tyr23 and Arg37 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.

Original languageEnglish (US)
Pages (from-to)13736-13741
Number of pages6
JournalJournal of Biological Chemistry
Issue number18
StatePublished - Apr 30 2010

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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