InterPro domain: IPR036423

Defects in the human SOD1 gene causes familial amyotrophic lateral sclerosis (Lou Gehrig's disease). Cytoplasmic and periplasmic SODs exist as dimers, whereas chloroplastic and extracellular enzymes exist as tetramers. Structural analysis supports the notion of independent functional evolution in prokaryotes (P-class) and eukaryotes (E-class) [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ].

Superoxide dismutases (SODs) are ubiquitous metalloproteins that prevent damage by oxygen-mediated free radicals by catalysing the dismutation of superoxide into molecular oxygen and hydrogen peroxide [ 9 ]. Superoxide is a normal by-product of aerobic respiration and is produced by a number of reactions, including oxidative phosphorylation and photosynthesis. The dismutase enzymes have a very high catalytic efficiency due to the attraction of superoxide to the ions bound at the active site [ 10 , 11 ].

There are three forms of superoxide dismutase, depending on the metal cofactor: Cu/Zn (which binds both copper and zinc), Fe and Mn types. The Fe and Mn forms are similar in their primary, secondary and tertiary structures, but are distinct from the Cu/Zn form [ 12 ]. Prokaryotes and protists contain Mn, Fe or both types, while most eukaryotic organisms utilise the Cu/Zn type. The Cu/Zn form has an immunoglobulin-like beta-sandwich fold.

1. Conserved patterns in the Cu,Zn superoxide dismutase family. J. Mol. Biol. 238, 366-86
2. Novel dimeric interface and electrostatic recognition in bacterial Cu,Zn superoxide dismutase. Proc. Natl. Acad. Sci. U.S.A. 93, 12774-9
3. Cu,Zn superoxide dismutase structure from a microbial pathogen establishes a class with a conserved dimer interface. J. Mol. Biol. 296, 145-53
4. A structure-based mechanism for copper-zinc superoxide dismutase. Biochemistry 38, 2167-78
5. Unusual trigonal-planar copper configuration revealed in the atomic structure of yeast copper-zinc superoxide dismutase. Biochemistry 35, 2316-21
6. The solution structure of reduced dimeric copper zinc superoxide dismutase. The structural effects of dimerization. Eur. J. Biochem. 269, 1905-15
7. Backbone dynamics of human Cu,Zn superoxide dismutase and of its monomeric F50E/G51E/E133Q mutant: the influence of dimerization on mobility and function. Biochemistry 39, 9108-18
8. Aspects of the structure, function, and applications of superoxide dismutase. CRC Crit. Rev. Biochem. 22, 111-80
9. Primary structure from amino acid and cDNA sequences of two Cu,Zn superoxide dismutase variants from Xenopus laevis. Arch. Biochem. Biophys. 272, 507-15
10. Atomic structures of wild-type and thermostable mutant recombinant human Cu,Zn superoxide dismutase. Proc. Natl. Acad. Sci. U.S.A. 89, 6109-13
11. Primary structure of porcine Cu,Zn superoxide dismutase. FEBS Lett. 186, 267-70
12. Characterization of iron superoxide dismutase cDNAs from plants obtained by genetic complementation in Escherichia coli. Proc. Natl. Acad. Sci. U.S.A. 87, 9903-7