Histone deacetylase
FunctionHistone deacetylase (HDAC) catalyzes the removal of acetyl group from ε-N-acetyl lysine in histones[1]. HDAC contains Zn. DNA expression is regulated by acetylation and de-acetylation. SAHA is a common inhibitor of HDAC. HDAC are classified according to their domain organization into 4 classes.
For HDAC8 see - Histone deacetylase 8 (HDAC8). For additional details see
RelevanceHDAC inhibitors are used in cancer therapy[4]. Sirtuins play a role in cancer, metabolic activity and neurodegenerative diseases[5]. HDAC inhibitor SAHA or Zolinza (Vorinostat) is used in the treatment of cutaneous T cell lymphoma[6]. Structural highlightsThe biological assembly of Human sirtuin-3 is . The between the 2 domains of SIRT3 - a large Rossman fold, NAD-binding domain and a small Zn-binding one)[7]. Water molecule shown as red sphere. 3D Structures of histone deacetylaseHistone deacetylase 3D structures
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ReferencesReferences
- ↑ Joshi P, Greco TM, Guise AJ, Luo Y, Yu F, Nesvizhskii AI, Cristea IM. The functional interactome landscape of the human histone deacetylase family. Mol Syst Biol. 2013;9:672. doi: 10.1038/msb.2013.26. PMID:23752268 doi:http://dx.doi.org/10.1038/msb.2013.26
- ↑ Parra M. Class IIa HDACs FEBS J. 2015 May;282(9):1736-44. PMID:25244360 doi:10.1111/febs.13061
- ↑ Schwer B, Verdin E. Conserved metabolic regulatory functions of sirtuins. Cell Metab. 2008 Feb;7(2):104-12. doi: 10.1016/j.cmet.2007.11.006. PMID:18249170 doi:http://dx.doi.org/10.1016/j.cmet.2007.11.006
- ↑ Marks P, Rifkind RA, Richon VM, Breslow R, Miller T, Kelly WK. Histone deacetylases and cancer: causes and therapies. Nat Rev Cancer. 2001 Dec;1(3):194-202. PMID:11902574 doi:http://dx.doi.org/10.1038/35106079
- ↑ Yamamoto H, Schoonjans K, Auwerx J. Sirtuin functions in health and disease. Mol Endocrinol. 2007 Aug;21(8):1745-55. Epub 2007 Apr 24. PMID:17456799 doi:http://dx.doi.org/10.1210/me.2007-0079
- ↑ Mann BS, Johnson JR, Cohen MH, Justice R, Pazdur R. FDA approval summary: vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist. 2007 Oct;12(10):1247-52. PMID:17962618 doi:http://dx.doi.org/10.1634/theoncologist.12-10-1247
- ↑ Jin L, Wei W, Jiang Y, Peng H, Cai J, Mao C, Dai H, Choy W, Bemis JE, Jirousek MR, Milne JC, Westphal CH, Perni RB. Crystal structures of human SIRT3 displaying substrate-induced conformational changes. J Biol Chem. 2009 Sep 4;284(36):24394-405. Epub 2009 Jun 16. PMID:19535340 doi:10.1074/jbc.M109.014928