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.