Glycoconjugate Journal

, Volume 31, Issue 6–7, pp 469–473 | Cite as

Flexibility and mutagenic resiliency of glycosyltransferases

  • Marie Lund Bay
  • Jose A. Cuesta-Seijo
  • Joel T. Weadge
  • Mattias Persson
  • Monica M. PalcicEmail author


The human blood group A and B antigens are synthesized by two highly homologous enzymes, glycosyltransferase A (GTA) and glycosyltransferase B (GTB), respectively. These enzymes catalyze the transfer of either GalNAc or Gal from their corresponding UDP-donors to αFuc1–2βGal-R terminating acceptors. GTA and GTB differ at only four of 354 amino acids (R176G, G235S, L266M, G268A), which alter the donor specificity from UDP-GalNAc to UDP-Gal. Blood type O individuals synthesize truncated or non-functional enzymes. The cloning, crystallization and X-ray structure elucidations for GTA and GTB have revealed key residues responsible for donor discrimination and acceptor binding. Structural studies suggest that numerous conformational changes occur during the catalytic cycle. Over 300 ABO alleles are tabulated in the blood group antigen mutation database (BGMUT) that provides a framework for structure-function studies. Natural mutations are found in all regions of GTA and GTB from the active site, flexible loops, stem region and surfaces remote from the active site. Our characterizations of natural mutants near a flexible loop (V175M), on a remote surface site (P156L), in the metal binding motif (M212V) and near the acceptor binding site (L232P) demonstrate the resiliency of GTA and GTB to mutagenesis.


Blood group glycosyltransferases Natural mutations 



Blood group A synthesizing α − 1,3-N-acetygalactosaminyltransferase


Blood group B synthesizing α-1,3-galactosyltransferase



This study was funded in part by a grant from FNU to M.M.P. Mette Bien is thanked for assistance with the characterization of the V212mutant.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Marie Lund Bay
    • 1
  • Jose A. Cuesta-Seijo
    • 1
  • Joel T. Weadge
    • 1
  • Mattias Persson
    • 1
  • Monica M. Palcic
    • 1
    Email author
  1. 1.Carlsberg LaboratoryCopenhagen VDenmark

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