Dissecting conformational contributions to glycosidase catalysis and inhibition

TY - JOUR

T1 - Dissecting conformational contributions to glycosidase catalysis and inhibition

AU - Speciale, Gaetono

AU - Thompson, Andrew James

AU - Davies, Gideon John

AU - Williams, Spencer J

N1 - © 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).

PY - 2014/10

Y1 - 2014/10

N2 - 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 enzymes bound to ligands that mimic the critical points, along with advanced computational methods and kinetic isotope effects are discussed.

AB - 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 enzymes bound to ligands that mimic the critical points, along with advanced computational methods and kinetic isotope effects are discussed.

U2 - 10.1016/j.sbi.2014.06.003

DO - 10.1016/j.sbi.2014.06.003

M3 - Article

SN - 0959-440X

VL - 28

SP - 1

EP - 13

JO - CURRENT OPINION IN STRUCTURAL BIOLOGY

JF - CURRENT OPINION IN STRUCTURAL BIOLOGY

IS - 1

ER -