title: How the flexibility of human histone deacetylases influences ligand binding: an overview.
abstract: 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.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet, 30, CH-1211 Geneva 4, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Deschamps
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet, 30, CH-1211 Geneva 4, Switzerland.
authors.forename: Claudia Avello
authors.initials: CA
authors.lastname: Simões-Pires
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet, 30, CH-1211 Geneva 4, Switzerland.
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Carrupt
authors.affiliation: 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.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Nurisso
mesh_terms: D000818:Animals; D001665:Binding Sites; D020134:Catalytic Domain; D015195:Drug Design; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D056572:Histone Deacetylase Inhibitors; D007527:Isoenzymes; D008024:Ligands; D006655:Histone Deacetylases