Dissecting conformational contributions to glycosidase catalysis and inhibition
Gaetano Speciale, Andrew J Thompson, Gideon J Davies, Spencer J Williams
Current Opinion in Structural Biology | CURRENT BIOLOGY LTD | Published : 2014
Glycoside hydrolases (GHs) are classified into >100 sequence-based families. These enzymes process a wide variety of complex carbohydrates with varying stereochemistry at the anomeric and other ring positions. The shapes that these sugars adopt upon binding to their cognate GHs, and the conformational changes that occur along the catalysis reaction coordinate is termed the conformational itinerary. Efforts to define the conformational itineraries of GHs have focussed upon the critical points of the reaction: substrate-bound (Michaelis), transition state, intermediate (if relevant) and product-bound. Recent approaches to defining conformational itineraries that marry X-ray crystallography of ..View full abstract
The Australian Research Council (ARC) is thanked for financial support. SJW highlights the generous support by the University of Melbourne and the ARC for a Future Fellowship, and thanks Dr Alessandro Soncini for assistance. AJT and GJD are supported by the Biotechnology and Biological Sciences Research Council and the European Research Council.