title: Detoxification of superoxide without production of H2O2: antioxidant activity of superoxide reductase complexed with ferrocyanide.
abstract: The superoxide radical O(2)(-.) is a toxic by-product of oxygen metabolism. Two O(2)(-.) detoxifying enzymes have been described so far, superoxide dismutase and superoxide reductase (SOR), both forming H2O2 as a reaction product. Recently, the SOR active site, a ferrous iron in a [Fe(2+) (N-His)(4) (S-Cys)] pentacoordination, was shown to have the ability to form a complex with the organometallic compound ferrocyanide. Here, we have investigated in detail the reactivity of the SOR-ferrocyanide complex with O(2)(-.) by pulse and gamma-ray radiolysis, infrared, and UV-visible spectroscopies. The complex reacts very efficiently with O(2)(-.). However, the presence of the ferrocyanide adduct markedly modifies the reaction mechanism of SOR, with the formation of transient intermediates different from those observed for SOR alone. A one-electron redox chemistry appears to be carried out by the ferrocyanide moiety of the complex, whereas the SOR iron site remains in the reduced state. Surprisingly, the toxic H2O2 species is no longer the reaction product. Accordingly, in vivo experiments showed that formation of the SOR-ferrocyanide complex increased the antioxidant capabilities of SOR expressed in an Escherichia coli sodA sodB recA mutant strain. Altogether, these data describe an unprecedented O(2)(-.) detoxification activity, catalyzed by the SOR-ferrocyanide complex, which does not conduct to the production of the toxic H2O2 species.
authors.affiliation: Département de Réponse et Dynamique Cellulaires/Laboratoire de Chimie et Biochimie des Centres Redox Biologiques, Unité Mixte de Recherche (UMR) 5047, CEA/CNRS, Université Joseph Fourier, 17 Avenue des Martyrs, 38054 Grenoble Cedex 9, France.
authors.forename: Fernando P
authors.initials: FP
authors.lastname: Molina-Heredia
authors.forename: Chantal
authors.initials: C
authors.lastname: Houée-Levin
authors.forename: Catherine
authors.initials: C
authors.lastname: Berthomieu
authors.forename: Danièle
authors.initials: D
authors.lastname: Touati
authors.forename: Emilie
authors.initials: E
authors.lastname: Tremey
authors.forename: Vincent
authors.initials: V
authors.lastname: Favaudon
authors.forename: Virgile
authors.initials: V
authors.lastname: Adam
authors.forename: Vincent
authors.initials: V
authors.lastname: Nivière
mesh_terms: D000332:Aerobiosis; D000975:Antioxidants / Q000378:metabolism*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D020564:Deltaproteobacteria / Q000201:enzymology*; D004926:Escherichia coli / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000378:metabolism; D005295:Ferrocyanides / Q000378:metabolism*; D005720:Gamma Rays; D006861:Hydrogen Peroxide / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress / Q000502:physiology; D010088:Oxidoreductases / Q000378:metabolism*; D011675:Pulse Radiolysis; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D013481:Superoxides / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D029968:Escherichia coli Proteins; D005295:Ferrocyanides; D012996:Solutions; D013481:Superoxides; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; C121849:superoxide reductase