Promiscuous scaffolds in proteins - non-native, non-additive and non-trivial

Abstract

Promiscuity, the ability of an enzyme to catalyze diverse activities using the same active site, sets up the stage for the evolution of complex organisms through gene duplication and specialization. The detection of promiscuous motifs is crucial to understand the physiological relevance of a protein, or for any endeavor that intends to rationally modify these latent capabilities to design new proteins under laboratory conditions. We have established a methodology for identifying catalytic residues based on spatial and electrostatic congruence with known active site configurations. Here, we discuss insights gained in several initiatives using our method on different enzymes.