Nature Structural Biology9, 685 - 690 (2002)
Published online: 19 August 2002; | doi:10.1038/nsb832
The structural basis for specificity in human ABO(H) blood group biosynthesis
Sonia I. Patenaude1, Nina O.L. Seto1, 2, Svetlana N. Borisova1, Adam Szpacenko3, Sandra L. Marcus3, Monica M. Palcic3
& Stephen V. Evans1
1
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, K1H 8M5 Canada.
2
Institute for Biological Sciences, National Research Council of Canada, Ottawa, K1A 0R6 Canada.
3
Department of Chemistry, University of Alberta, Edmonton, T6G 2G2 Canada.
Correspondence should be addressed to Stephen V. Evans evans@uottawa.ca
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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