Mechanistic Insight into Enzymatic Glycosyl Transfer with Retention of Configuration through Analysis of Glycomimetic Inhibitors

Abstract

Structural “valid”-ation: The mechanism of enzyme-catalyzed glycosyl transfer with retention of anomeric configuration continues to baffle, a situation compounded by the lack of insightful 3-D structures of ternary enzyme complexes. Synthesis and multi-dimensional kinetic analysis of validoxylamine derivatives are used to access the 3-D structure of a ternary complex (see picture; U=uridyl) providing insight into the geometry and donor–acceptor interplay at the glycosyltransfer site.