ABSTRACT
It is now apparent that most cells in eukaryotic organisms probably contain Cu/Zn SOD and that the enzyme may play an important role in shielding intracellular components from oxidative damage. For reviews, see [1] and [7-10]. Eukaryotic SODs normally exist as homodimers with two subunits each containing some 150 amino acids and an overall molecular weight of around 32 kDa, but prokaryotic SODs can be monomeric or dimeric. There is considerable sequence homology among the SODs from the various species so far examined and within the mammalian specieshuman, rat, pig and horse-the homology is around 80%. The residues directly or indirectly involved in metal binding appear to be completely conserved. The X-ray structure of bovine erythrocyte Cu/Zn SOD was reported in the early 1980s at a resolution of 2.0 A [11,12] (PDB code: 2SOD). In this structure, the two identical subunits, each containing 151 residues, are related by a crystallographic twofold axis,
o so that the active sites are facing away from each other giving a distance of 33.8 A between the copper atoms. Within each subunit the polypeptide chain is folded into two 4-stranded antiparallel p sheets (cf. the topology of the cupredoxin fold in the chapter describing the multi-copper oxidases) which then pack together to form a flattened cylinder. Figure 2 shows the main chain topology for one subunit in the dimer as well as the positions of the two metal atoms. The first sheet is composed of strands 1, 2, 3, and 6 and the second of strands 5, 4, 7, and 8. The overall motif formed by the seven strands, 2 - 8 inclusive, is almost identical to that found in the immu noglobulins [13]. The active site Cu and Zn atoms are located at the bottom of a deep cleft on the outside of the subunit. The cleft is formed by two large loops, one between strands 4 and 5 and the second between strands 7 and 8.
