Synthesis of the acceptor analog alphaFuc(1-->2)alphaGal-O(CH2)7 CH3: a probe for the kinetic mechanism of recombinant human blood group B glycosyltransferase

Glycoconj J. 1999 Oct;16(10):599-606. doi: 10.1023/a:1007072832421.

Abstract

We report the chemical synthesis of alphaFuc(1-->2)alphaGal-O(CH2)7CH3 (1) an analog of the natural blood group (O)H disaccharide alphaFuc(1-->2)betaGal-OR. Compound 1 was a good substrate for recombinant blood group B glycosyltransferase (GTB) and was used as a precursor for the enzymatic synthesis of the blood group B analog (alphaGal(-->3)alphaFuc(1-->2)]alphaGal-O(CH2)7CH3+ ++ (2). To probe the mechanism of the GTB reaction, kinetic evaluations were carried out employing compound 1 or the natural acceptor disaccharide alphaFuc(1-->2)betaGal-O(CH2)7CH3 (3) with UDP-Gal and UDP-GalNAc donors. Comparisons of the kinetic constants for alternative donor and acceptor pairs suggest that the GTB mechanism is Theorell-Chance where donor binding precedes acceptor binding. GTB operates with retention of configuration at the anomeric center of the donor. Retaining reactions are thought to occur via a double-displacement mechanism with formation of a glycosyl-enzyme intermediate consistent with the proposed Theorell-Chance mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ABO Blood-Group System
  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Catalysis
  • Disaccharides / chemical synthesis*
  • Disaccharides / chemistry
  • Disaccharides / metabolism*
  • Galactosyltransferases / metabolism*
  • Glycosylation
  • Humans
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Molecular Sequence Data
  • Protein Binding
  • Recombinant Proteins / metabolism
  • Substrate Specificity
  • Trisaccharides / chemistry
  • Trisaccharides / metabolism
  • Uridine Diphosphate Galactose / metabolism

Substances

  • ABO Blood-Group System
  • Disaccharides
  • Fuc(1-2)Gal-O(CH2)7-CH3
  • Recombinant Proteins
  • Trisaccharides
  • Uridine Diphosphate Galactose
  • Galactosyltransferases
  • blood-group-substance alpha-D-galactosyltransferase