The molecular mechanism of enzymatic glycosyl transfer with retention of configuration: evidence for a short-lived oxocarbenium ion-like species

摘要

The catalytic mechanism of nucleotide-sugar dependent glycosyltransferases (GTs), especially those that act with retention of anomeric configuration, remains one of the most intriguing unanswered questions in the field of glycobiology. In contrast to the well-characterized mechanistic strategies used by glycoside hydrolases (GHs) to catalyze the cleavage of glycosidic bonds, the mechanisms of retaining GTs remain unclear [1]. Double displacement mechanisms have been proposed (but not fully proved) by analogy to retaining GHs. In addition, many GTs do not have a putative nucleophile protein residue. This prompted some authors to suggest an unusual mechanism, in which the reaction proceeds via a front side single displacement. This mechanism, usually named as SN_i or SN_i-like in the literature, has been surrounded by a strong controversy, since in principle it implies that two covalent bonds are forming and breaking, respectively, in the same region of space.