Structures of the superoxide reductase from Pyrococcus furiosus in the oxidized and reduced states

Superoxide reductase (SOR) is a blue non-heme iron protein that functions i n anaerobic microbes as a defense mechanism against reactive oxygen species by catalyzing the reduction of superoxide to hydrogen peroxide [Jenney, F. E., Jr., Verhagen, M. F. J. M., Cui, X., and Adams, M. W. W. (1999) Scienc e 286, 306-309]. Crystal structures of SOR from the hyperthermophilic archa eon Pyrococcus furiosus have been determined in the oxidized and reduced fo rms to resolutions of 1.7 and 2.0 Angstrom, respectively. SOR forms a homot etramer, with each subunit adopting an immunoglobulin-like beta-barrel fold that coordinates a mononuclear, non-heme iron center. The protein fold and metal center are similar to those observed previously for the homologous p rotein desulfoferrodoxin from Desulfovibrio desulfuricans [Coelho, A. V., M atias, P., Fulop, V., Thompson, A., Gonzalez, A., and Carrondo, M. A. (1997 ) J. Bioinorg. Chem. 2, 680-689]. Each iron is coordinated to imidazole nit rogens of four histidines in a planar arrangement, with a cysteine ligand o ccupying an axial position normal to this plane. In two of the subunits of the oxidized structure, a glutamate carboxylate serves as the sixth ligand to form an overall six-coordinate, octahedral coordinate environment. In th e remaining two subunits, the sixth coordination site is either vacant or o ccupied by solvent molecules. The iron centers in all four subunits of the reduced structure exhibit pentacoordination. The structures of the oxidized and reduced forms of SOR suggest a mechanism by which superoxide accessibi lity may be controlled and define a possible binding site for rubredoxin, t he likely physiological electron donor to SOR.