Generation of blood group specificity: New insights from structural studies on the complexes of A- and B-reactive saccharides with basic winged bean agglutinin

Kulkarni, Kiran A and Katiyar, Samiksha and Surolia, Avadhesha and Vijayan, Mamannamana and Suguna, Kaza (2007) Generation of blood group specificity: New insights from structural studies on the complexes of A- and B-reactive saccharides with basic winged bean agglutinin. In: Proteins: Structure, Function, and Bioinformatics, 68 (3). pp. 762-769.

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Abstract

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.

Item Type:	Journal Article
Publication:	Proteins: Structure, Function, and Bioinformatics
Publisher:	Wiley-Liss
Additional Information:	Copyright of this article belongs to Wiley-Liss.
Keywords:	Legume lectin;Crystal structure;Proteinsugar interaction;Interaction and conformation
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	26 Sep 2007
Last Modified:	19 Sep 2010 04:39
URI:	http://eprints.iisc.ac.in/id/eprint/11932

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