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.
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Acknowledgments
This work was supported by the Structural Genomics Consortium (SGC). The SGC is a registered charity (number 1097737) that receives funds from the Canadian Institutes for Health Research, the Canadian Foundation for Innovation, Genome Canada through the Ontario Genomics Institute, GlaxoSmithKline, Karolinska Institutet, the Knut and Alice Wallenberg Foundation, the Ontario Innovation Trust, the Ontario Ministry for Research and Innovation, Merck & Co., Inc., the Novartis Research Foundation, the Swedish Agency for Innovation Systems, the Swedish Foundation for Strategic Research, and the Wellcome Trust.
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Schapira, M. (2011). Structural Biology of Human Metal-Dependent Histone Deacetylases. In: Yao, TP., Seto, E. (eds) Histone Deacetylases: the Biology and Clinical Implication. Handbook of Experimental Pharmacology, vol 206. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-21631-2_10
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DOI: https://doi.org/10.1007/978-3-642-21631-2_10
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