Computational study of the non-heme iron active site in superoxide reductase and its reaction with superoxide

Inorg Chem. 2003 Jan 27;42(2):446-56. doi: 10.1021/ic025684l.

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.

Publication types

  • Comparative Study

MeSH terms

  • Binding Sites
  • Cytochrome P-450 Enzyme System / chemistry
  • Cytochrome P-450 Enzyme System / metabolism
  • Databases, Factual
  • Desulfovibrio vulgaris / enzymology*
  • Ferrous Compounds / chemistry*
  • Ferrous Compounds / metabolism
  • Iron / chemistry*
  • Ligands
  • Models, Molecular*
  • Molecular Conformation
  • Molecular Structure
  • Oxidation-Reduction
  • Oxidoreductases / chemistry*
  • Oxidoreductases / metabolism
  • Pyrococcus furiosus / enzymology*
  • Water / chemistry
  • X-Ray Diffraction

Substances

  • Ferrous Compounds
  • Ligands
  • Water
  • Cytochrome P-450 Enzyme System
  • Iron
  • Oxidoreductases
  • superoxide reductase