Computational Studies of Glycoside, Carboxylic Ester, and Thioester Hydrolase Mechanisms: A Review

This article is a review of computational work over the last ∼15 years to elucidate the catalytic mechanisms of three major enzyme classes: glycoside hydrolases, carboxylic ester hydrolases, and thioesterases. The mechanisms of glycoside hydrolases that both invert and retain the configuration of the anomeric carbon atom of the labile glycosidic bond are covered, as is the twisting of the glycosidic bond exerted by members of different glycoside hydrolase families. The hydrolytic mechanisms and substrate binding of five different carboxylic ester hydrolase classes—acetylcholinesterases, butyrylcholinesterases, cocaine esterases, carboxylesterases, and triacylglycerol lipases—are addressed. Finally, the mechanism of members of a thioesterase family with HotDog tertiary structures is covered.