title: The AidB component of the Escherichia coli adaptive response to alkylating agents is a flavin-containing, DNA-binding protein.
abstract: Upon exposure to alkylating agents, Escherichia coli increases expression of aidB along with three genes (ada, alkA, and alkB) that encode DNA repair proteins. In order to begin to identify the role of AidB in the cell, the protein was purified to homogeneity, shown to possess stoichiometric amounts of flavin adenine dinucleotide (FAD), and confirmed to have low levels of isovaleryl-coenzyme A (CoA) dehydrogenase activity. A homology model of an AidB homodimer was constructed based on the structure of a four-domain acyl-CoA oxidase. The predicted structure revealed a positively charged groove connecting the two active sites and a second canyon of positive charges in the C-terminal domain, both of which could potentially bind DNA. Three approaches were used to confirm that AidB binds to double-stranded DNA. On the basis of its ability to bind DNA and its possession of a redox-active flavin, AidB is predicted to catalyze the direct repair of alkylated DNA.
authors.affiliation: Microbiology and Molecular Genetics, 6193 Biomedical Physical Sciences, Michigan State University, East Lansing, MI 48824-4320, USA.
authors.forename: Mukta S
authors.initials: MS
authors.lastname: Rohankhedkar
authors.forename: Scott B
authors.initials: SB
authors.lastname: Mulrooney
authors.forename: William J
authors.initials: WJ
authors.lastname: Wedemeyer
authors.forename: Robert P
authors.initials: RP
authors.lastname: Hausinger
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D005182:Flavin-Adenine Dinucleotide / Q000737:chemistry*; D050769:Isovaleryl-CoA Dehydrogenase / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA
chemical_list: C090096:AidB protein, E coli; D000477:Alkylating Agents; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D005182:Flavin-Adenine Dinucleotide; D050769:Isovaleryl-CoA Dehydrogenase