Catalyzing Carbohydrate Cleavage: Glycosidases and Their Mechanisms

Abstract

Glycoside hydrolases, “glycosidases”, catalyze carbohydrate catabolism, remodeling, and signaling by accelerating glycosidic-bond cleavage by more than 17 orders of magnitude. Distributed across every kingdom of life and grouped into over 180 sequence-defined families, these enzymes exhibit exceptional diversity in fold, mechanism, and physiological function, and many also catalyze transglycosylation or phosphorolysis. The classical Koshland paradigms─stereochemical inversion, enzymatic nucleophile-assisted retention, and substrate-assisted retention─are analyzed with an emphasis on the conformational itineraries and oxocarbenium ion-like transition states revealed by kinetic isotope effects..