Journal article
How the flexibility of human histone deacetylases influences ligand binding: an overview.
- Deschamps N School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet, 30, CH-1211 Geneva 4, Switzerland.
- Simões-Pires CA School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet, 30, CH-1211 Geneva 4, Switzerland.
- Carrupt PA School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet, 30, CH-1211 Geneva 4, Switzerland.
- Nurisso A School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet, 30, CH-1211 Geneva 4, Switzerland. Electronic address: alessandra.nurisso@unige.ch.
- 2015-01-20
Published in:
- Drug discovery today. - 2015
Animals
Binding Sites
Catalytic Domain
Drug Design
Histone Deacetylase Inhibitors
Histone Deacetylases
Humans
Isoenzymes
Ligands
Models, Molecular
Protein Binding
Protein Conformation
Structure-Activity Relationship
Substrate Specificity
English
Over the past decade, human histone deacetylases (HDACs) have become interesting as therapeutic targets because of the benefits that their modulation might provide in aging-related disorders. Recently, studies using crystallography and computational chemistry have provided information on the structure and conformational changes related to HDAC-mediated recognition events. Through the description of the key mass and one-off movements observed in metal-dependent HDACs, here we highlight the impact of flexibility on drug-binding affinity and specificity. The collected information will be useful for not only a better understanding of the biological functions of HDACs, but also the conception of new selective binders.
- Language
-
- English
- Open access status
- closed
- Identifiers
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- DOI 10.1016/j.drudis.2015.01.004
- PMID 25597521
- Persistent URL
- https://sonar.ch/global/documents/245917
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