Molecular recognition of a human blood group determinant by a plant lectin

Abstract

The lectin IV of Griffoniasimplicifolia (GS4) specifically binds the terminal tetrasaccharide unit of the Lewis b human blood group determinant (Le^b). The single crystal X-ray analysis of the complex with Le^b-OMe has demonstrated that the binding site on the lectin is a shallow depression with a negatively charged aspartate side chain at the bottom of the cavity. In addition to this aspartate, a serine and an asparagine side chain provide the polar groups that hydrogen bond to the three hydroxyl groups of Le^b, which has been termed the key polar grouping for complex formation. A notable characteristic of the binding site is that five aromatic amino acid side chains (one Phe, two Tyr, and two Trp residues) surround these polar interactions and make van der Waals contacts with the tetrasaccharide. Thus, as predicted from previous solution binding studies, extensive nonpolar interactions are involved, which contribute importantly both to the specificity of the reaction and the stability of the noncovalent complex that is formed. These results represent the first structural example of the molecular recognition of a human blood group determinant by the receptor site of a protein. Extensive sequence homology exists between GS4 and the concanavalin A (Con A), pea, and favin lectins. The main hydrophilic groups of the carbohydrate-binding site of GS4 and Con A are aspartate, asparagine, and serine residues; the homology suggests that the serine is replaced by asparagine in the case of the pea and favin lectins. It appears probable that these two latter lectins possess very similar, if not identical, specificities. Keywords: lectin, carbohydrate, molecular recognition, binding.