ARCHITECTURE OF THE SUGAR BINDING-SITES IN CARBOHYDRATE-BINDING PROTEINS - A COMPUTER MODELING STUDY

Different sugars, Gal, GalNAc and Man were docked at the monosaccharid e binding sites of Erythrina corallodenron (EcorL), peanut lectin (PNA ), Lathyrus ochrus (LOLI), and pea lectin (PSL). To study the lectin-c arbohydrate interactions, in the complexes, the hydroxymethyl group in Man and Gal favors, gg and gt conformations respectively, and is the dominant recognition determination. The monosaccharide binding site in lectins that are specific to Gal/GalNAc is wider due to the additiona l amino acid residues in loop D as compared to that in lectins specifi c to Man/Glc, and affects the hydrogen bonds of the sugar involving re sidues from loop D, but not its orientation in the binding site. The i nvariant amino acid residues Asp from loop A, and Asn and an aromatic residue (Phe or Tyr) in loop C provides the basic architecture to reco gnize the common features in C4 epimers. The invariant Gly in loop B t ogether with one or two residues in the variable region of loop D/A ho lds the sugar tightly at both ends. Loss of any one of these hydrogen bonds leads to weak interaction. While the subtle variations in the se quence and conformation of peptide fragment that resulted due to the s ize and location of gaps present in amino acid sequence in the neighbo rhood of the sugar binding site of loop D/A seems to discriminate the binding of sugars which differ at C4 atom (galacto and gluco configura tions). The variations at loop B are important in discriminating Gal a nd GalNAc binding. The present study thus provides a structural basis for the observed specificities of legume lectins which uses the same f our invariant residues for binding. These studies also bring out the i nformation that is important for the design/engineering of proteins wi th the desired carbohydrate specificity. (C) 1998 Elsevier Science B.V . All rights reserved.