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Minimizing the Entropy Penalty for Ligand Binding: Lessons from the Molecular Recognition of the Histo Blood‐Group Antigens by Human Galectin‐3
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 bind...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619289/ https://www.ncbi.nlm.nih.gov/pubmed/30942512 http://dx.doi.org/10.1002/anie.201900723 |
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author | Gimeno, Ana Delgado, Sandra Valverde, Pablo Bertuzzi, Sara Berbís, Manuel Alvaro Echavarren, Javier Lacetera, Alessandra Martín‐Santamaría, Sonsoles Surolia, Avadhesha Cañada, Francisco Javier Jiménez‐Barbero, Jesus Ardá, Ana |
author_facet | Gimeno, Ana Delgado, Sandra Valverde, Pablo Bertuzzi, Sara Berbís, Manuel Alvaro Echavarren, Javier Lacetera, Alessandra Martín‐Santamaría, Sonsoles Surolia, Avadhesha Cañada, Francisco Javier Jiménez‐Barbero, Jesus Ardá, Ana |
author_sort | Gimeno, Ana |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6619289 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-66192892019-07-22 Minimizing the Entropy Penalty for Ligand Binding: Lessons from the Molecular Recognition of the Histo Blood‐Group Antigens by Human Galectin‐3 Gimeno, Ana Delgado, Sandra Valverde, Pablo Bertuzzi, Sara Berbís, Manuel Alvaro Echavarren, Javier Lacetera, Alessandra Martín‐Santamaría, Sonsoles Surolia, Avadhesha Cañada, Francisco Javier Jiménez‐Barbero, Jesus Ardá, Ana Angew Chem Int Ed Engl Communications 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. John Wiley and Sons Inc. 2019-04-17 2019-05-27 /pmc/articles/PMC6619289/ /pubmed/30942512 http://dx.doi.org/10.1002/anie.201900723 Text en © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Communications Gimeno, Ana Delgado, Sandra Valverde, Pablo Bertuzzi, Sara Berbís, Manuel Alvaro Echavarren, Javier Lacetera, Alessandra Martín‐Santamaría, Sonsoles Surolia, Avadhesha Cañada, Francisco Javier Jiménez‐Barbero, Jesus Ardá, Ana Minimizing the Entropy Penalty for Ligand Binding: Lessons from the Molecular Recognition of the Histo Blood‐Group Antigens by Human Galectin‐3 |
title | Minimizing the Entropy Penalty for Ligand Binding: Lessons from the Molecular Recognition of the Histo Blood‐Group Antigens by Human Galectin‐3 |
title_full | Minimizing the Entropy Penalty for Ligand Binding: Lessons from the Molecular Recognition of the Histo Blood‐Group Antigens by Human Galectin‐3 |
title_fullStr | Minimizing the Entropy Penalty for Ligand Binding: Lessons from the Molecular Recognition of the Histo Blood‐Group Antigens by Human Galectin‐3 |
title_full_unstemmed | Minimizing the Entropy Penalty for Ligand Binding: Lessons from the Molecular Recognition of the Histo Blood‐Group Antigens by Human Galectin‐3 |
title_short | Minimizing the Entropy Penalty for Ligand Binding: Lessons from the Molecular Recognition of the Histo Blood‐Group Antigens by Human Galectin‐3 |
title_sort | minimizing the entropy penalty for ligand binding: lessons from the molecular recognition of the histo blood‐group antigens by human galectin‐3 |
topic | Communications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619289/ https://www.ncbi.nlm.nih.gov/pubmed/30942512 http://dx.doi.org/10.1002/anie.201900723 |
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