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 <i>TRP4</i> in <i>Saccharomyces cerevisiae</i> , revealed that Ser121, identified in structural studies as critical for substrate binding, is not required for two documented <i>in vivo</i> functions. These findings add functional complexity to the Trp4 active site beyond crystallographic characterization.