title: Flavorubredoxin, an inducible catalyst for nitric oxide reduction and detoxification in Escherichia coli.
abstract: Nitric oxide (NO) is a poison, and organisms employ diverse systems to protect against its harmful effects. In Escherichia coli, ygaA encodes a transcription regulator (b2709) controlling anaerobic NO reduction and detoxification. Adjacent to ygaA and oppositely transcribed are ygaK (encoding a flavorubredoxin (flavoRb) (b2710) with a NO-binding non-heme diiron center) and ygbD (encoding a NADH:(flavo)Rb oxidoreductase (b2711)), which function in NO reduction and detoxification. Mutation of either ygaA or ygaK eliminated inducible anaerobic NO metabolism, whereas ygbD disruption partly impaired the activity. NO-sensitive [4Fe-4S] (de)hydratases, including the Krebs cycle aconitase and the Entner-Doudoroff pathway 6-phosphogluconate dehydratase, were more susceptible to inactivation in ygaK or ygaA mutants than in the parental strain, and these metabolic poisonings were associated with conditional growth inhibitions. flavoRb (NO reductase) and flavohemoglobin (NO dioxygenase) maximally metabolized and detoxified NO in anaerobic and aerobic E. coli, respectively, whereas both enzymes scavenged NO under microaerobic conditions. We suggest designation of the ygaA-ygaK-ygbD gene cluster as the norRVW modulon for NO reduction and detoxification.
authors.affiliation: Division of Critical Care Medicine, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Gardner
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Helmick
authors.forename: Paul R
authors.initials: PR
authors.lastname: Gardner
mesh_terms: D000154:Aconitate Hydratase / Q000494:pharmacology; D002875:Chromosomes / Q000235:genetics; D004251:DNA Transposable Elements; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics*; D006836:Hydro-Lyases / Q000378:metabolism / Q000494:pharmacology; D008957:Models, Genetic; D008958:Models, Molecular; D005810:Multigene Family; D016296:Mutagenesis; D009154:Mutation; D009569:Nitric Oxide / Q000378:metabolism*; D009876:Operon; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D004251:DNA Transposable Elements; D029968:Escherichia coli Proteins; D014157:Transcription Factors; C451400:YgaK protein, E coli; D009569:Nitric Oxide; D006836:Hydro-Lyases; C022362:phosphogluconate dehydratase; D000154:Aconitate Hydratase