Cu,Zn Superoxide Dismutase (SOD) is regularly a homodimeric enzyme, whose Greek-key topology and structure are well preserved throughout the evolutionary phyla. Seven 3D structures of eukaryotic SODs have highlighted these concepts and provided the structural bases for the study of the catalytic mechanism, of substrate electrostatic guidance, of structural/thermal stability and of the high affinity in subunit association.

In prokaryotic SODs this pattern is altered by amino acid insertions/deletions and mutations which occur in loop regions, altering the active site electrostatics and the subunit association properties.

We have recently determined the 3D structure of E.coli SOD at 2.0 Å resolution, and that of a new form of P. leiognathi SOD at 2.1 Å resolution. In agreement with solution studies, we found that E.coli SOD provides the first known example of a SOD which is fully active in the monomeric state. The region of molecular surface potentially involved in the dimerization contacts is highly polar in E.Coli SOD and displays a perturbed 3D structure, hampering the assembly of the enzyme in a dimeric form. On the other hand, P.leiognathi SOD, which also displays a polar patch on the molecular surface involved in subunit association in the eukaryotic SODs, is found as a dimeric enzyme. In this bacterial dimeric SOD, the association of subunits is therefore based on an entirely new association surface which buries several intervening water molecules.

Comparison of the different dimeric assemblies and of the monomeric structure of E.coli SOD, allows to underscore some general principles for the funcionality of an enzyme which, in the framework of a reasonably conserved protein fold topology, adopts different assembly rules in organisms which are not necessarily distant along the evolutionary scale.
Engineering studies on P.leiognathi SOD mutants at the subunit interface are in progress.