Small detail makes big difference

The glycosyltransferase enzymes GTA and GTB produce the A and B antigens on human erythrocytes, but the precise biochemistry involved in the specific interaction with substrate molecules has been unclear. In August 19 Nature Structural Biology, Sonia Patenaude and colleagues at the University of Ottawa, Canada, describe the structural basis for distinct ABO(H) blood group biosynthesis in humans (Nat Struct Biol 2002, DOI:10.1038/nsb832).

Patenaude et al. examined the crystal structures of cloned GTA and GTB at a resolution of 1.8-1.32Å, in both free solution and in complex with their disaccharide H-antigen acceptor and UDP-N-acetylgalactosamine donor. They observed that only two of the critical amino acid residues of the enzymes are positioned to contact donor or acceptor substrates. In addition, 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....