Structure and DNA binding of alkylation response protein AidB

Journal Article · Mon Jan 12 04:00:00 EST 2009 · Proc. Natl. Acad. Sci. USA

DOI:https://doi.org/10.1073/pnas.0806521105· OSTI ID:1006912

Bowles, Timothy; Metz, Audrey H; O'Quin, Jami; Wawrzak, Zdzislaw; Eichman, Brandt F ^[1]

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1. Vanderbilt

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-{angstrom} 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.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1006912
• Journal Information: Proc. Natl. Acad. Sci. USA, Journal Name: Proc. Natl. Acad. Sci. USA Journal Issue: (40) ; 10, 2008 Vol. 105; ISSN PNASA6; ISSN 0027-8424
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
ADA
ADENINES
ALKYLATING AGENTS
ALKYLATION
CRYSTAL STRUCTURE
DAMAGE
DNA
DNA REPAIR
ESCHERICHIA COLI
ISOALLOXAZINES
OXIDOREDUCTASES
PROTEINS