QM/MM Insight on Enzymatic Reactions of Glycosyltransferases

Glycosyltransferases comprise a group of enzymes that catalyze the transfer of glycosyl residues from donors containing nucleoside phosphates to other molecules. The molecular details of the catalytic mechanism involving these enzymes are not well understood. Hybrid QM/MM methods have become important in providing new insights into the atomic details of enzymatic reactions. The QM/MM calculations of GnT-I and β4GalT-1 show that inverting glycosyltransferases utilize an SN2 type mechanism, with one amino acid functioning as a base catalyst. In addition, the computed transition state structures provide a rational basis for the design of transition state analog inhibitors.