Mutation of a conserved anthranilate phosphoribosyltransferase active site residue supports tryptophan biosynthesis in vivo

Enzymes contributing to amino acid metabolism are among the most ancient in the proteome. A growing appreciation that many of these proteins have evolved to contribute multiple, distinct functions has led to an increased focus on defining such moonlighting molecules and their diverse roles. A focus on the metabolic enzyme anthranilate phosphoribosyltransferase, encoded by TRP4 in Saccharomyces cerevisiae , revealed that Ser121, identified in structural studies as critical for substrate binding, is not required for two documented in vivo functions. These findings add functional complexity to the Trp4 active site beyond crystallographic characterization.