Glycosyltransferases: structures, functions, and mechanisms

Annu Rev Biochem. 2008;77:521-55. doi: 10.1146/annurev.biochem.76.061005.092322.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bacillus subtilis / metabolism
  • Carbohydrates / chemistry
  • Enzymes / chemistry
  • Evolution, Molecular
  • Genomics
  • Glycomics
  • Glycosylation
  • Glycosyltransferases / chemistry*
  • Glycosyltransferases / physiology*
  • Humans
  • Ions
  • Molecular Conformation
  • Protein Conformation
  • Protein Folding
  • Protein Structure, Secondary


  • Carbohydrates
  • Enzymes
  • Ions
  • Glycosyltransferases