Sugar conformations that enhance cleavage of glycosidic bonds in carbohydrate-active enzymes

Abstract

Carbohydrate-active enzymes select particular conformations of one sugar of their carbohydrate substrates to enhance catalysis. The evolution of this conformation during catalysis, known as the catalytic itinerary, is of fundamental interest in glycobiology. Here we calculate the free energy landscape of β- xylose to predict the possible catalytic itineraries of β-xylan enzymes. Our results discard one of the three catalytic itineraries proposed on the basis of X-ray structures of mutant enzymes. Additional classical and quantum mechanics/molecular mechanics (QM/MM) calculations indicate that complexes obtained from modified enzymes do not necessarily represent the structures that take place in the reaction coordinate.