A single point mutation reverses the donor specificity of human blood group B-synthesizing galactosyltransferase

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DOIResolve DOI: http://doi.org/10.1074/jbc.M212002200
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TypeArticle
Journal titleJournal Of Biological Chemistry
Volume278
Issue14
Pages1240312405; # of pages: 3
AbstractBlood group A and B antigens are carbohydrate structures that are synthesized by glycosyltransferase enzymes. The final step in B antigen synthesis is carried out by an α1–3 galactosyltransferase (GTB) that transfers galactose from UDP-Gal to type 1 or type 2, αFuc1→2βGal-R (H)-terminating acceptors. Similarly the A antigen is produced by an α1–3N-acetylgalactosaminyltransferase that transfersN-acetylgalactosamine from UDP-GalNAc to H-acceptors. Human α1–3 N-acetylgalactosaminyltransferase and GTB are highly homologous enzymes differing in only four of 354 amino acids (R176G, G235S, L266M, and G268A). Single crystal x-ray diffraction studies have shown that the latter two of these amino acids are responsible for the difference in donor specificity, while the other residues have roles in acceptor binding and turnover. Recently a novelcis-AB allele was discovered that produced A and B cell surface structures. It had codons corresponding to GTB with a single point mutation that replaced the conserved amino acid proline 234 with serine. Active enzyme expressed from a synthetic gene corresponding to GTB with a P234S mutation shows a dramatic and complete reversal of donor specificity. Although this enzyme contains all four “critical” amino acids associated with the production of blood group B antigen, it preferentially utilizes the blood group A donor UDP-GalNAc and shows only marginal transfer of UDP-Gal. The crystal structure of the mutant reveals the basis for the shift in donor specificity.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); NRC Institute for Biological Sciences
Peer reviewedNo
NRC numberMARCUS2003
NPARC number9360243
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Record identifierd29cce49-e3d7-4121-b1aa-54e794fa6f20
Record created2009-07-10
Record modified2016-05-09
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