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 language | English |
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Pages (from-to) | 521-555 |
Number of pages | 35 |
Journal | Annual Review of Biochemistry |
Volume | 77 |
DOIs | |
Publication status | Published - 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