Intramolecular epistasis correlates with divergence of specificity in promiscuous and bifunctional NSAR/OSBS enzymes.

ABSTRACT: Understanding the functions and evolution of specificity-determining residues is essential for improving strategies to predict and design enzyme functions. Whether the function of an amino acid residue is retained during evolution depends on intramolecular epistasis, which occurs when the same residue contributes to different phenotypes in different genetic backgrounds. This study examines the relationship between epistasis and functional divergence by investigating a conserved specificity determinant in five homologs from the N-succinylamino acid racemase (NSAR)/o-succinylbenzoate synthase (OSBS) subfamily. NSAR activity originated as a promiscuous (non-biological) activity of an ancestral OSBS. Some extant NSAR/OSBS subfamily enzymes still have OSBS activity as a biological function and

SUBMITTER: Truong DP 

PROVIDER: S-EPMC12006748 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature