Minimizing the Entropy Penalty for Ligand Binding: Lessons from the Molecular Recognition of the Histo Blood-Group Antigens by Human Galectin-3.
Angew Chem Int Ed Engl
; 58(22): 7268-7272, 2019 05 27.
Article
en En
| MEDLINE
| ID: mdl-30942512
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Termodinámica
/
Antígenos de Grupos Sanguíneos
/
Entropía
/
Galectina 3
/
Fucosa
Límite:
Humans
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Año:
2019
Tipo del documento:
Article
País de afiliación:
España