STRUCTURAL BASIS OF GALACTOSE RECOGNITION BY C-TYPE ANIMAL LECTINS

The asialoglycoprotein receptors and many other C-type (Ca2+-dependent ) animal lectins specifically recognize galactose- or N-acetylgalactos amine-terminated oligosaccharides. Analogous binding specificity can b e engineered into the homologous rat mannose-binding protein A by chan ging three amino acids and inserting a glycine-rich loop (Iobst, S. T, , and Drickamer, K. (1994) J. Biol, Chem. 269, 15512-15519), Crystal s tructures of this mutant complexed with beta-methyl galactoside and N- acetylgalactosamine (GalNAc) reveal that as with wild-type mannose-bin ding proteins, the 3- and 4-OH groups of the sugar directly coordinate Ca2+ and form hydrogen bonds with amino acids that also serve as Ca2 ligands, The different stereochemistry of the 3- and 4-OH groups in m annose and galactose, combined with a fixed Ca2+ coordination geometry , leads to different pyranose ring locations in the two cases. The gly cine-rich loop provides selectivity against mannose by holding a criti cal tryptophan in a position optimal for packing with the apolar face of galactose but incompatible with mannose binding, The 2-acetamido su bstituent of GalNAc is in the vicinity of amino acid positions identif ied by site-directed mutagenesis (Iobst, S. T,, and Drickamer, K. (199 6) J, Biol, Chem. 271, 6686-6693) as being important for the formation of a GalNAc-selective binding site.