S36: Privileged scaffolds, "underlying" promiscuity, and convergence in the evolution of new enzyme functions

Investigation of structure-function relationships in large and functionally diverse enzyme superfamilies suggests that many evolve multiple reactions using "privileged" scaffolds, structural templates whose active site architectures facilitate catalysis of common partial reactions or other chemical capabilities. Natural evolution has used such scaffolds to evolve many different reactions and reaction specificities  consistent with these functional capabilities. Using protein similarity networks, a global view of these relationships  now reveals  new insights  about how new functions evolve and illustrates how an "underlying promiscuity" observed in these superfamilies can inform the functional assignment of proteins of unknown function and guide the choice of starting structures for enzyme engineering in the lab. Consistent with these findings, these global studies also allow us to identify convergent evolution of specific enzyme functions from different intermediate ancestors in the lineage of several of these superfamilies.