Divergent evolution of enzymatic function: Mechanistically diverse superfamilies and functionally distinct suprafamilies

The protein sequence and structure databases are now sufficiently represent ative that strategies nature uses to evolve new catalytic functions can be identified. Groups of divergently related enzymes whose members catalyze di fferent reactions but share a common partial reaction, intermediate, or tra nsition state (mechanistically diverse superfamilies) have been discovered, including the enolase, amidohydrolase, thiyl radical, crotonase, vicinal-o xygen-chelate, and Fe-dependent oxidase superfamilies. Other groups of dive rgently related enzymes whose members catalyze different overall reactions that do not share a common mechanistic strategy (functionally distinct supr afamilies) have also been identified: (a) functionally distinct suprafamili es whose members catalyze successive transformations in the tryptophan and histidine biosynthetic pathways and (b) functionally distinct suprafamilies whose members catalyze different reactions in different metabolic pathways . An understanding of the structural bases for the catalytic diversity obse rved in super- and suprafamilies may provide the basis for discovering the functions of proteins and enzymes in new genomes as well as provide guidanc e for in vitro evolution/engineering of new enzymes.