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The structural basis for specificity in human ABO(H) blood group biosynthesis

Nature Structural Biology volume 9, pages 685–690 (2002)Cite this article

Abstract

The human ABO(H) blood group antigens are produced by specific glycosyltransferase enzymes. An N-acetylgalactosaminyltransferase (GTA) uses a UDP-GalNAc donor to convert the H-antigen acceptor to the A antigen, whereas a galactosyltransferase (GTB) uses a UDP-galactose donor to convert the H-antigen acceptor to the B antigen. GTA and GTB differ only in the identity of four critical amino acid residues. Crystal structures at 1.8–1.32 Å resolution of the GTA and GTB enzymes both free and in complex with disaccharide H-antigen acceptor and UDP reveal the basis for donor and acceptor specificity and show that only two of the critical amino acid residues are positioned to contact donor or acceptor substrates. Given the need for stringent stereo- and regioselectivity in this biosynthesis, these structures further demonstrate that the ability of the two enzymes to distinguish between the A and B donors is largely determined by a single amino acid residue.

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Figure 1: SETOR35 diagram of GTB structure.
Figure 2: Active site of GTB
Figure 3: Substrates versus critical amino acids.
Figure 4: Candidate enzyme nucleophile.

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Acknowledgements

S.I.P. and S.V.E. thank the Canadian Institutes of Health Research for salary support and funding. M.M.P. thanks the Natural Sciences and Engineering Research Council of Canada for funding. The authors thank D.R. Bundle and O. Hindsgaul for helpful discussions, as well as C. Weeks, J. Berendzen and R.W. Grosse-Kuntsleeve for help while at Brookhaven National Laboratories beamlines X4A, X8C and X12C.

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Authors and Affiliations

  1. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, K1H 8M5, Canada

    Sonia I. Patenaude, Nina O.L. Seto, Svetlana N. Borisova & Stephen V. Evans

  2. Institute for Biological Sciences, National Research Council of Canada, Ottawa, K1A 0R6, Canada

    Nina O.L. Seto

  3. Department of Chemistry, University of Alberta, Edmonton, T6G 2G2, Canada

    Adam Szpacenko, Sandra L. Marcus & Monica M. Palcic

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  1. Sonia I. Patenaude
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Correspondence to Stephen V. Evans.

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Patenaude, S., Seto, N., Borisova, S. et al. The structural basis for specificity in human ABO(H) blood group biosynthesis. Nat Struct Mol Biol 9, 685–690 (2002). https://doi.org/10.1038/nsb832

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