Glycosyltransferases: structures, functions, and mechanisms.
Glycosyltransferases catalyze glycosidic bond formation using sugar donors containing a nucleoside phosphate or a lipid phosphate leaving group. Only two structural folds, GT-A and GT-B, have been identified for the nucleotide sugar-dependent enzymes, but other folds are now appearing for the soluble domains of lipid phosphosugar-dependent glycosyl transferases. Structural and kinetic studies have provided new insights. Inverting glycosyltransferases utilize a direct displacement S(N)2-like mechanism involving an enzymatic base catalyst. Leaving group departure in GT-A fold enzymes is typically facilitated via a coordinated divalent cation, whereas GT-B fold enzymes instead use positively charged side chains and/or hydroxyls and helix dipoles. The mechanism of retaining glycosyltransferases is less clear. The expected two-step double-displacement mechanism is rendered less likely by the lack of conserved architecture in the region where a catalytic nucleophile would be expected. A mechanism involving a short-lived oxocarbenium ion intermediate now seems the most likely, with the leaving phosphate serving as the base.
Department of Chemistry, University of British Columbia, Vancouver, BC, Canada. llairson@scripps.edu
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D000818:Animals; D001412:Bacillus subtilis / Q000378:metabolism; D002241:Carbohydrates / Q000737:chemistry; D004798:Enzymes / Q000737:chemistry; D019143:Evolution, Molecular; D023281:Genomics; D054794:Glycomics; D006031:Glycosylation; D016695:Glycosyltransferases / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D007477:Ions; D008968:Molecular Conformation; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary
D002241:Carbohydrates; D004798:Enzymes; D007477:Ions; D016695:Glycosyltransferases