The structural basis for specificity in human ABO(H) blood group biosynthesis.
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 A 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.
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, K1H 8M5 Canada.
Sonia I
SI
Patenaude
Nina O L
NO
Seto
Svetlana N
SN
Borisova
Adam
A
Szpacenko
Sandra L
SL
Marcus
Monica M
MM
Palcic
Stephen V
SV
Evans
D000017:ABO Blood-Group System; D018360:Crystallography, X-Ray; D005700:Galactosyltransferases / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D017350:N-Acetylgalactosaminyltransferases / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D013379:Substrate Specificity; D014530:Uridine Diphosphate / Q000378:metabolism
D000017:ABO Blood-Group System; D014530:Uridine Diphosphate; D005700:Galactosyltransferases; D017350:N-Acetylgalactosaminyltransferases; C003742:UDPgalactosamine-galactose acetylgalactosaminyltransferase; C023155:blood-group-substance alpha-D-galactosyltransferase