The basic disaccharide structure recognized by galectin family members is the lactosamine-like structure Galβ1-4(3)Glc(NAc). The 32-kDa galectin LEC-1 of the nematode Caenorhabditis elegans is composed of two domains, each of which is homologous to vertebrate 14-kDa-type galectins. The N-terminal lectin domain of LEC-1 recognizes blood group A saccharide (GalNAcα1-3(Fucα1-2)Galβ1-3GlcNAc), whereas this saccharide is poorly recognized by the C-terminal domain. Using a combination of site-directed mutagenesis and analysis of the sugar-binding profile by frontal affinity chromatography, we previously found that Thr41 in the N-terminal lectin domain of LEC-1 is important for its affinity for A-hexasaccharide. Thr41 is located on β-strand S3, next to the three β-strands S4—S6, where the conserved amino acids form the binding site for the basic Galβ1-4(3)Glc(NAc) structure. Here, we report that a second amino acid, Asp133, in the N-terminal lectin domain of LEC-1, located on the β-strand S2 adjacent to that containing Thr41, is important for LEC-1-specific recognition of A-hexasaccharide. These results suggest that amino acid residues other than those located on the three β-strands S4—S6, contribute to the unique sugar binding specificity of individual galectins.
2008 The Pharmaceutical Society of Japan