Tryptophan Synthase Uses an Atypical Mechanism To Achieve Substrate Specificity.

ABSTRACT: Tryptophan synthase (TrpS) catalyzes the final steps in the biosynthesis of l-tryptophan from l-serine (Ser) and indole-3-glycerol phosphate (IGP). We report that native TrpS can also catalyze a productive reaction with l-threonine (Thr), leading to (2S,3S)-?-methyltryptophan. Surprisingly, ?-substitution occurs in vitro with a 3.4-fold higher catalytic efficiency for Ser over Thr using saturating indole, despite a >82000-fold preference for Ser in direct competition using IGP. Structural data identify a novel product binding site, and kinetic experiments clarify the atypical mechanism of specificity: Thr binds efficiently but decreases the affinity for indole and disrupts the allosteric signaling that regulates the catalytic cycle.

SUBMITTER: Buller AR 

PROVIDER: S-EPMC5207025 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature