The iron-and manganese-containing superoxide dismutases (Fe/Mn-SOD) share the same chemical function and spatial structure but can be distinguished according to their modes of oligomerization and their metal ion specificity. They appear as homodimers or homotetramers and usually require a specific metal for activity. On the basis of 261 aligned SOD sequences and 12 superimposed x-ray structures, two phenetic trees were constructed, one sequence-based and the other structurebased. Their comparison reveals the imperfect correlation of sequence and structural changes; hyperthermophilicity requires the largest sequence alterations, whereas dimer/tetramer and manganese/iron specificities are induced by the most sizable structural differences within the monomers. A systematic investigation of sequence and structure characteristics conserved in all aligned SOD sequences or in subsets sharing common oligomeric and/or metal specificities was performed. Several residues were identified as guaranteeing the common function and dimeric conformation, others as determining the tetramer formation, and yet others as potentially responsible for metal specificity. Some form cation-interactions between an aromatic ring and a fully or partially positively charged group, suggesting that these interactions play a significant role in the structure and function of SOD enzymes. Dimer/tetramer-and iron/manganese-specific fingerprints were derived from the set of conserved residues; they can be used to propose selected residue substitutions in view of the experimental validation of our in silico derived hypotheses.

The structural principals of proteins are reviewed and analysed from a geometric perspective with a view to revealing the underlying regularities in their construction. Computer methods for the automatic comparison and classification of these structures are then reviewed with an analysis of the statistical significance of comparing different shapes. Following an analysis of the current state of the classification of proteins, more abstract geometric and topological representations are explored, including the occurrence of knotted topologies. The review concludes with a consideration of the origin of higher-level symmetries in protein structure.

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We introduce a completely automatic and objective procedure for the comparison of protein structures. A genetic algorithm is used to search for a near optimal solution of the rigid-body superposition of two whole protein structures. The specification of an initial set of equivalences is not required. Topological equivalences in the final structural alignment are defined by a conventional dynamic programming routine, which is commonly used to compare protein sequences. A least-squares fitting algorithm is then used to optimize the fit between the final set of equivalences. We have applied our method to the comparison of ribonucleic acid structures, as well as protein structures. The structural alignments are generally consistent with those previously published. In fact, on most occasions our method defines at least the same number of topological equivalences as other procedures, but always with a lower r.m.s. distance between them.

Three major improvements to a previously described method for automatic protein structure comparison are described. First, a limit to translations for the rigid-body superposition is now assigned according to the dimensions of the structures being compared. Second, examination of the effect of the gap penalty on the derivation of a sequence alignment corresponding to a given structure superposition has led to a method to evaluate alternative structure-based sequence alignments. Third, the pairwise procedure has been generalized to multiple structure alignment. This implementation of rigid-body superposition can recognize well documented distant relationships which hitherto have required consideration of additional features and properties as well as those relationships between proteins of different sizes. A much larger common scaffold or framework between six globins can be extracted than that obtained using a standard algorithm for multiple structure superposition.