Gimeno, Ana and Delgado, Sandra and Valverde, Pablo and Bertuzzi, Sara and Alvaro Berbis, Manuel and Echavarren, Javier and Lacetera, Alessandra and Martin-Santamaria, Sonsoles and Surolia, Avadhesha and Canada, Francisco Javier and Jimenez-Barbero, Jesus and Arda, Ana (2019) Minimizing the Entropy Penalty for Ligand Binding: Lessons from the Molecular Recognition of the Histo Blood-Group Antigens by Human Galectin-3. In: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 58 (22). pp. 7268-7272.
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Abstract
Ligand conformational entropy plays an important role in carbohydrate recognition events. Glycans are characterized by intrinsic flexibility around the glycosidic linkages, thus in most cases, loss of conformational entropy of the sugar upon complex formation strongly affects the entropy of the binding process. By employing a multidisciplinary approach combining structural, conformational, binding energy, and kinetic information, we investigated the role of conformational entropy in the recognition of the histo blood-group antigens A and B by human galectin-3, a lectin of biomedical interest. We show that these rigid natural antigens are pre-organized ligands for hGal-3, and that restriction of the conformational flexibility by the branched fucose (Fuc) residue modulates the thermodynamics and kinetics of the binding process. These results highlight the importance of glycan flexibility and provide inspiration for the design of high-affinity ligands as antagonists for lectins.
| Item Type: | Journal Article |
|---|---|
| Publication: | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION |
| Publisher: | WILEY-V C H VERLAG GMBH |
| Additional Information: | copyright for this article belongs to WILEY-V C H VERLAG GMBH |
| Keywords: | blood-group antigen; conformational entropy; glycans; lectins; molecular recognition |
| Department/Centre: | Division of Biological Sciences > Molecular Biophysics Unit |
| Date Deposited: | 05 Aug 2019 06:44 |
| Last Modified: | 05 Aug 2019 06:44 |
| URI: | http://eprints.iisc.ac.in/id/eprint/63383 |
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