Minimizing the Entropy Penalty for Ligand Binding: Lessons from the Molecular Recognition of the Histo Blood‐Group Antigens by Human Galectin‐3

• DOI: 10.1002/anie.201900723
• Publication Date: 2019-04-03T14:11:37Z
• Authors: Ana Gimeno; Sandra Delgado; Pablo Valverde; Sara Bertuzzi; Manuel Alvaro Berbís; Javier Echavarren; Alessandra Lacetera; Sonsoles Martín‐S...; Avadhesha Surolia; Francisco Javier ...; Jesus Jiménez‐Bar...; Ana Ardá
• Keywords: Conformational entropy; Glycosidic bond; Molecular Recognition; Galectin

Ligand conformational entropy plays an important role in carbohydrate recognition events. Glycans are characterized by intrinsic flexibility around the glycosidic linkages, thus most cases, loss of sugar upon complex formation strongly affects binding process. By employing a multidisciplinary approach combining structural, conformational, energy, and kinetic information, we investigated histo blood-group antigens A B human galectin-3, lectin biomedical interest. We show that these rigid natural pre-organized ligands for hGal-3, restriction branched fucose (Fuc) residue modulates thermodynamics kinetics These results highlight importance glycan provide inspiration design high-affinity as antagonists lectins.