Copper‐Zinc Superoxide Dismutase in Prokaryotes and Eukaryotes

Abstract

Cu,Zn superoxide dismutases (SODs) are ubiquitous enzymes catalyzing the conversion of superoxide radical anions into O 2 and H 2 O 2 . In eukaryotes, Cu,Zn SOD is a dimeric protein (2 × 16 k Da); each protomer hosts the binuclear Cu,Zn catalytic center. In prokaryotes, Cu,Zn SODs can be monomeric or dimeric, their quaternary structure differing from that of the eukaryotic homologs. The protein tertiary structure (based on an eight‐stranded antiparallel β‐barrel) is conserved through species. Crystal structures and mutational analysis indicate that Cu,Zn SOD activity is based on a redox cycle, whereby the catalytic Cu(II) species is first reduced (to Cu(I)), and then oxidized (back to Cu(II)) by successive encounters with the substrate. The Zn ion plays a key structural role in maintaining active site structural integrity during the catalytic cycle. Efficient electrostatic steering of the anionic substrate to the active site accounts for the very high (diffusion limited) catalytic turnover displayed by all Cu,Zn SODs. Mutations in human cytoplasmic Cu,Zn SOD have been related to the onset of FALS (familial amyotrophic lateral sclerosis , or Lou Gehring disease), a fatal motoneuron degenerative disease.

Regulatory and Structural Differences in the Cu,Zn-Superoxide Dismutases of Salmonella enterica and Their Significance for Virulence

“…Although these proteins catalyze the same reaction, two groups have reported that the sodCI and sodCII genes are not interchangeable, suggesting that the two proteins have distinctive structural or functional properties (23,24). SodCI exhibits the highest catalytic rate ever observed in a natural Cu,Zn-SOD (27), but Cu,Zn-SODs in general are characterized by very high catalytic rates (28,29). More significantly, SodCI is a dimeric protein, whereas SodCII is a monomer (16).…”

NMR assignment of reduced form of copper, zinc superoxide dismutase from Salmonella enterica

“…Several Cu,ZnSODs from eukaryotic and prokaryotic sources have been characterized either by X-ray crystallography (Bordo et al 2001) or NMR spectroscopy (Banci et al 1998). All these enzymes derive from a common ancestor gene.…”

A Thiazole Analogue Exhibits an Anti-Proliferative Effect in Different Human Carcinoma Cell Lines and Its Mechanism Based on Molecular Modeling

“…Local positive charge attracts a series of small anions that bind directly to Cu in place of the solvent molecule then extend in the direction of the conserved Arg143 [15]. In reduction status, Cu is thought to release the His63 ligand it shared with the Zn ion and departing O2, to allow its conformation to become trigonal and roughly planar.…”