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Generation of blood group specificity: New insights from structural studies on the complexes of A‐ and B‐reactive saccharides with basic winged bean agglutinin
Author(s) -
Kulkarni Kiran A.,
Katiyar Samiksha,
Surolia Avadhesha,
Vijayan Mamannamana,
Suguna Kaza
Publication year - 2007
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21428
Subject(s) - chemistry , lectin , hydrogen bond , residue (chemistry) , stereochemistry , agglutinin , ligand (biochemistry) , oligosaccharide , trisaccharide , binding site , biochemistry , molecule , receptor , organic chemistry
Basic winged bean agglutinin binds A‐blood group substance with higher affinity and B‐blood group substance with lesser affinity. It does not bind the O substance. The crystal structures of the lectin, complexed with A‐reactive and B‐reactive di and tri saccharides, have been determined. In addition, the complexes of the lectin with fucosylated A‐trisaccharides and B‐trisaccharides and with a variant of the A‐trisaccharide have been modeled. These structures and models provide valuable insights into the structural basis of blood group specificities. All the four carbohydrate binding loops of the lectin contribute to the primary combining site while the loop of variable length contributes to the secondary binding site. In a significant advance to the current understanding, the interactions at the secondary binding site also contribute substantially, albeit in a subtle manner, to determine the blood group specificity. Compared with the interactions of the B‐trisaccharide with the lectin, the third sugar residue of the A‐reactive trisacharide forms an additional hydrogen bond with a lysine residue in the variable loop. In the former, the formation of such a hydrogen bond is prevented by a shift in the orientation of third sugar resulting from an internal hydrogen bond in it. The formation of this bond is also facilitated by an interaction dependent change in the rotamer conformation of the lysyl residue of the variable loop. Thus, the difference in the interactions at the secondary site is generated by coordinated movements in the ligand as well as the protein. A comparison of the crystal structure and the model of the complex involving the variant of the A‐trisaccharide results in the delineation of the relative contributions of the interactions at the primary and the secondary sites in determining blood group specificity. Proteins 2007. © 2007 Wiley‐Liss, Inc.