Structural insights into the catalytic mechanism and transition state of glycosyltransferases using ab initio molecular modeling

Glycosyltransferases are found in most living organisms, and they are involved in the biosynthesis of carbohydrates catalyzing the transfer of a saccharide residue to a specific acceptor. Despite the important roles that carbohydrates play in numerous biological events, the molecular details of the catalytic mechanism of these enzymes are generally not well understood, and consequently the progress in development of therapeutics based on their inhibitions has been relatively slow. High-level quantum mechanical calculations can be used to gain some insight into characteristics of the enzymatic reactions, and they lead to a deeper understanding of glycosyltransferases catalysis. In addition, the computed transition state structures provide a rational basis for design of transition state analog inhibitors.