Evolution of structure and function in the o ‐succinylbenzoate synthase family

Abstract

Understanding how protein function and structure evolve is vital for redesigning proteins and utilizing data from genome projects. In pursuit of this goal, we analyzed the evolution of structure and function in the o-succinylbenzoate synthase (OSBS) family, which is in the enolase superfamily. Although OSBSs are extremely divergent and can share < 15% identity, phylogenetic analysis indicates that they have a single evolutionary origin. However, no sequence or structural motifs unique to the OSBS family could be identified; all residues conserved in the OSBS family are also found in enolase superfamily members that have different functions. In addition, the N- and C-terminal domains are oriented differently in three crystallized OSBSs. Thus, although function has been conserved in this family, the precise mode of subtrate binding and determining specificity has not. Included in the OSBS family tree are several uncharacterized proteins that group with the promiscuous OSBS/N-acylamino acid racemase from Amycolatopsis. These probably have additional or alternative functions to OSBS because many are from organisms lacking the pathway in which OSBS is an intermediate. Several of these are promiscuous, like the Amycolatopsis enzyme, supporting the hypothesis that new protein functions evolve through promiscuous intermediates. These are found in taxonomically diverse species, including both Eubacteria and Archaea, suggesting that this new protein function has been transmitted by lateral gene transfer. This work was funded by NIH Grants GM60595 and GM071790.