title: Computational study of the non-heme iron active site in superoxide reductase and its reaction with superoxide.
abstract: The ferrous square-pyramidal [Fe(NHis)4(SCys)] site of superoxide reductases (SORs) has been shown to reduce superoxide at a nearly diffusion-controlled rate. The final products of the reaction are hydrogen peroxide and the ferric hexacoordinated SOR site, with a carboxylate group from a conserved glutamate serving as the sixth ligand trans to the cysteine sulfur. A transient intermediate absorbing at approximately 600 nm in the reaction of the ferrous pentacoordinated site with superoxide has been proposed to be a ferric-(hydro)peroxo complex (Coulter, E.; Emerson, J.; Kurtz, D. M., Jr.; Cabelli, D. J. Am. Chem. Soc. 2000, 122, 11555-11556.). In the present study, DFT and ZINDO/S-CI results are shown to support the description of the 600-nm intermediate as an end-on, low-spin ferricperoxo or--hydroperoxo complex. Side-on peroxo coordination was found to be significantly less stable than end-on because of constraints on the imidazole ligand ring orientations imposed mostly by the protein. The modeled ferric-hydroperoxo complex had a decidedly nonplanar CysC beta-S-Fe-O-O geometry that appears to be imposed by the same constraints. A single prominent visible absorption of the (hydro)peroxo model is shown to be due mainly to a CysS-->Fe(III) pi charge transfer (CT) transition with a minor portion of His-->Fe(III) pi CT character and very little peroxo-->Fe(III) CT character. On the basis of calculations of models with various mono- and diprotonated peroxo ligands, protonation of the iron-bound peroxo oxygen is a key step in the decay of the ferric(hydro)peroxo complex favoring release of hydrogen peroxide over cleavage of the O-O bond, as occurs in the heme structural analogue, cytochrome P450.
authors.affiliation: Department of Chemistry, Center for Metalloenzyme Studies, University of Georgia, Athens, Georgia 30602, USA.
authors.forename: Radu
authors.initials: R
authors.lastname: Silaghi-Dumitrescu
authors.forename: Ioan
authors.initials: I
authors.lastname: Silaghi-Dumitrescu
authors.forename: Eric D
authors.initials: ED
authors.lastname: Coulter
authors.forename: Donald M
authors.initials: DM
authors.lastname: Kurtz
mesh_terms: D001665:Binding Sites; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism; D016208:Databases, Factual; D016969:Desulfovibrio vulgaris / Q000201:enzymology*; D005296:Ferrous Compounds / Q000737:chemistry* / Q000378:metabolism; D007501:Iron / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry* / Q000378:metabolism; D020027:Pyrococcus furiosus / Q000201:enzymology*; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D005296:Ferrous Compounds; D008024:Ligands; D014867:Water; D003577:Cytochrome P-450 Enzyme System; D007501:Iron; D010088:Oxidoreductases; C121849:superoxide reductase