Natural and recombinant A and B gene encoded glycosyltransferases.
The human blood group A and B synthesizing enzymes are glycosyltransferases that catalyse the transfer of a monosaccharide residue from UDP-GalNAc and UDP-Gal donors, respectively, to alphaFuc1,2-Gal terminated blood group H acceptors. Extensive investigations of their substrate specificity and physical properties have been carried out since their initial discovery. These studies demonstrated a rigid specificity for the acceptor structure, crossover in donor specificity and immunological similarity along with chromatographic differences. Cloning of the enzymes has shown that they are highly homologous, differing in only four of their 354 amino acids. Changing the residues Arg176-->Gly, Gly235-->Ser, Leu266-->Met and Gly 268-->Ala converts the enzyme specificity from blood group A to blood group B glycosyltransferase. Structure function investigations have been carried out by systematic interchange and modification of these four critical amino acids. These studies have shown that donor specificity is attributed to the last two amino acids. Mutants have also been produced with greatly enhanced turnover rates as well as hybrid A/B enzymes that catalyse both reactions efficiently.
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Department of Chemistry, University of Alberta, Edmonton, Alberta Canada T6G 2G2.
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Hindsgaul
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D000017:ABO Blood-Group System; D000818:Animals; D002240:Carbohydrate Sequence; D003001:Cloning, Molecular; D005544:Forecasting; D005700:Galactosyltransferases / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D014644:Genetic Variation; D006801:Humans; D007700:Kinetics; D008322:Mammals / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism; D025942:Oligosaccharides, Branched-Chain; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D014312:Trisaccharides / Q000378:metabolism
D000017:ABO Blood-Group System; D009844:Oligosaccharides; D025942:Oligosaccharides, Branched-Chain; D011993:Recombinant Fusion Proteins; D014312:Trisaccharides; C101335:blood group A trisaccharide; C406478:blood group B trisaccharide; D005700:Galactosyltransferases; D017350:N-Acetylgalactosaminyltransferases; C003742:UDPgalactosamine-galactose acetylgalactosaminyltransferase; C023155:blood-group-substance alpha-D-galactosyltransferase