title: Avoiding high-valent iron intermediates: superoxide reductase and rubrerythrin.
abstract: The Fenton or Fenton-type reaction between aqueous ferrous ion and hydrogen peroxide generates a highly oxidizing species, most often formulated as hydroxyl radical or ferryl ([Fe(IV)O](2+)). Intracellular Fenton-type chemistry can be lethal if not controlled. Nature has, therefore, evolved enzymes to scavenge superoxide and hydrogen peroxide, the reduced dioxygen species that initiate intracellular Fenton-type chemistry. Two such enzymes found predominantly in air-sensitive bacteria and archaea, superoxide reductase (SOR) and rubrerythrin (Rbr), functioning as a peroxidase (hydrogen peroxide reductase), contain non-heme iron. The iron coordination spheres in these enzymes contain five or six protein ligands from His and Glu residues, and, in the case of SOR, a Cys residue. SOR contains a mononuclear active site that is designed to protonate and rapidly expel peroxide generated as a product of the enzymatic reaction. The ferrous SOR reacts adventitiously but relatively slowly (several seconds to a few minutes) with exogenous hydrogen peroxide, presumably in a Fenton-type reaction. The diferrous active site of Rbr reacts more rapidly with hydrogen peroxide but can divert Fenton-type reactions towards the two-electron reduction of hydrogen peroxide to water. Proximal aromatic residues may function as radical sinks for Fenton-generated oxidants. Fenton-initiated damage to these iron active sites may become apparent only under extremely oxidizing intracellular conditions.
authors.affiliation: Department of Chemistry and Center for Metalloenzyme Studies, University of Georgia, Athens, GA 30602, USA. kurtz@chem.uga.edu
authors.forename: Donald M
authors.initials: DM
authors.lastname: Kurtz
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D005288:Ferredoxins / Q000737:chemistry* / Q000378:metabolism; D005290:Ferric Compounds / Q000737:chemistry / Q000378:metabolism; D005296:Ferrous Compounds / Q000737:chemistry / Q000378:metabolism; D006422:Hemerythrin; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism; D007501:Iron / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D019159:Nonheme Iron Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D012416:Rubredoxins
chemical_list: D001426:Bacterial Proteins; D005288:Ferredoxins; D005290:Ferric Compounds; D005296:Ferrous Compounds; D006422:Hemerythrin; D019159:Nonheme Iron Proteins; D012416:Rubredoxins; C055857:rubrerythrins; C066317:ferryl iron; D006861:Hydrogen Peroxide; D007501:Iron; D010088:Oxidoreductases; C121849:superoxide reductase