How the Superoxide Dismutase Protein Specifies the Reactivity of Bound Fe

University Of Kentucky Research Foundation, Lexington KY

Investigators

Abstract

Mn-superoxide dismutase and Fe-superoxide dismutase (MnSOD and FeSOD) catalize alternating one-electron oxidation and reduction of the superoxide anion (O2 -), to molecular oxygen and hydrogen peroxide (O2 and H2O2). These enzymes extend our healthy life, and are closely related to enzymes that mediate degradation of toxic wastes, and synthesis of antibiotics. This research seeks to understand the determinants of SOD's catalytic activity. Previous work has shown that the SOD proteins can tune the reduction midpoint potential, Em , of the bound Fe2+/3+ or Mn2+/3+ ion over more than half a volt, thus providing potential access to a wide range of chemistry. The protein has been proposed to achieve this via hydrogen bonding between a conserved active site glutamine and a coordinated solvent molecule. The spectroscopic, structural and thermodynamic studies, on native enzymes and a few mutants, will elucidate the mechanism and magnitude of this hydrogen bonding's effect on the Em. In addition, the first characterizations of Mn-substituted FeSOD, whose Em is higher than 900 mV, will be carried out. This research will test a rational, chemical mechanism for redox tuning in metalloproteins. Many metalloenzymes besides SOD include a solvent molecule among the metal ion ligands, and as a rule this solvent also hydrogen bonds with protein residues. Thus, understanding gained as to the magnitude of redox tuning this can afford, and the extent to which it can be manipulated, will have general applicability.