title: Structural biology of human metal-dependent histone deacetylases.
abstract: Class I, II, and IV histone deacetylases (HDACs) are metal-dependent enzymes involved in a broad and partly unexplored array of biological mechanisms that include epigenetic control of gene expression. The catalytic domain of human classes I and IIa enzymes has been solved in complex with a substrate peptide and inhibitors, which revealed a conserved architecture, uncovered the catalytic mechanism of deacetylation, and outlined a chemical framework for inhibitor design. We will review the different structural elements of metal-dependent HDACs and their contributions to substrate recognition, catalysis, and inhibitor specificity.
authors: Structural Genomics Consortium and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. matthieu.schapira@utoronto.ca
authors: Matthieu
authors: M
authors: Schapira
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D002384:Catalysis; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008670:Metals; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D056572:Histone Deacetylase Inhibitors; D008670:Metals; D006655:Histone Deacetylases