Glycosyltransferases: Structures, functions, and mechanisms

L. L. Lairson, B. Henrissat, G. J. Davies, S. G. Withers

Research output: Contribution to journalLiterature reviewpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)521-555
Number of pages35
JournalAnnual Review of Biochemistry
Volume77
DOIs
Publication statusPublished - 2008

Keywords

  • carbohydrate-modifying enzymes
  • glycobiology
  • glycosylation
  • ion pair mechanisms
  • nucleophilic substitution
  • N-ACETYLGLUCOSAMINYLTRANSFERASE-I
  • COLI MALTODEXTRIN PHOSPHORYLASE
  • LIVER-GLYCOGEN PHOSPHORYLASE
  • RAY CRYSTAL-STRUCTURE
  • PASTEURELLA-MULTOCIDA SIALYLTRANSFERASE
  • RETAINING ALPHA-GALACTOSYLTRANSFERASE
  • DIMETHYLALLYL DIPHOSPHATE ISOMERASE
  • PHAGE BETA-GLUCOSYLTRANSFERASE
  • GROUP-B GLYCOSYLTRANSFERASES
  • BASE-FLIPPING MECHANISM

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