Structure and DNA binding of alkylation response protein AidB

Timothy Bowles, Audrey H. Metz, Jami O'Quin, Zdzislaw Wawrzak, Brandt F. Eichman

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Exposure of Escherichia coli to alkylating agents activates expression of AidB in addition to DNA repair proteins Ada, AlkA, and AlkB. AidB was recently shown to possess a flavin adenine dinucleotide (FAD) cofactor and to bind to dsDNA, implicating it as a flavin-dependent DNA repair enzyme. However, the molecular mechanism by which AidB acts to reduce the mutagenic effects of specific DNA alkylators is unknown. We present a 1.7-Å crystal structure of AidB, which bears superficial resemblance to the acyl-CoA dehydrogenase superfamily of flavoproteins. The structure reveals a unique quaternary organization and a distinctive FAD active site that provides a rationale for AidB's limited dehydrogenase activity. A highly electropositive C-terminal domain not present in structural homologs was identified by mutational analysis as the DNA binding site. Structural analysis of the DNA and FAD binding sites provides evidence against AidB-catalyzed DNA repair and supports a model in which AidB acts to prevent alkylation damage by protecting DNA and destroying alkylating agents that have yet to reach their DNA target.

Original languageEnglish (US)
Pages (from-to)15299-15304
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number40
DOIs
StatePublished - Oct 7 2008

Keywords

  • Acyl-CoA dehydrogenase
  • Adaptive response
  • DNA repair
  • Flavin adenine dinucleotide

ASJC Scopus subject areas

  • General

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