title: Widespread distribution in pathogenic bacteria of di-iron proteins that repair oxidative and nitrosative damage to iron-sulfur centers.
abstract: Expression of two genes of unknown function, Staphylococcus aureus scdA and Neisseria gonorrhoeae dnrN, is induced by exposure to oxidative or nitrosative stress. We show that DnrN and ScdA are di-iron proteins that protect their hosts from damage caused by exposure to nitric oxide and to hydrogen peroxide. Loss of FNR-dependent activation of aniA expression and NsrR-dependent repression of norB and dnrN expression on exposure to NO was restored in the gonococcal parent strain but not in a dnrN mutant, suggesting that DnrN is necessary for the repair of NO damage to the gonococcal transcription factors, FNR and NsrR. Restoration of aconitase activity destroyed by exposure of S. aureus to NO or H2O2 required a functional scdA gene. Electron paramagnetic resonance spectra of recombinant ScdA purified from Escherichia coli confirmed the presence of a di-iron center. The recombinant scdA plasmid, but not recombinant plasmids encoding the complete Escherichia coli sufABCDSE or iscRSUAhscBAfdx operons, complemented repair defects of an E. coli ytfE mutant. Analysis of the protein sequence database revealed the importance of the two proteins based on the widespread distribution of highly conserved homologues in both gram-positive and gram-negative bacteria that are human pathogens. We provide in vivo and in vitro evidence that Fe-S clusters damaged by exposure to NO and H2O2 can be repaired by this new protein family, for which we propose the name repair of iron centers, or RIC, proteins.
authors.affiliation: School of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Tim W
authors.initials: TW
authors.lastname: Overton
authors.forename: Marta C
authors.initials: MC
authors.lastname: Justino
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Joana M
authors.initials: JM
authors.lastname: Baptista
authors.forename: Ana M P
authors.initials: AM
authors.lastname: Melo
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Cole
authors.forename: Lígia M
authors.initials: LM
authors.lastname: Saraiva
mesh_terms: D000154:Aconitate Hydratase / Q000235:genetics / Q000378:metabolism; D001419:Bacteria / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005816:Genetic Complementation Test; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007506:Iron-Sulfur Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009344:Neisseria gonorrhoeae / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology; D010802:Phylogeny; D010957:Plasmids / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D007506:Iron-Sulfur Proteins; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D000154:Aconitate Hydratase