Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Curr Opin Chem Biol. 2022 Oct;70:102179. doi: 10.1016/j.cbpa.2022.102179. Epub 2022 Jul 6.
Classical histone deacetylases (HDACs) are enzymes that can hydrolytically cleave acetyl-Lys in histones and other proteins and serve as established drug targets in some forms of cancer. Class I HDACs 1-3 typically exist in a range of multiprotein complexes inside cells and show distinct biological functions in modulating gene expression. In recent years, it has become possible to purify and analyze the structure and enzymatic properties of several of these HDAC complexes, including CoREST, MiDAC, NuRD, Sin3, SMRT, MIER, and RERE. Here, we summarize what is experimentally established and/or computationally predicted about the structure of these complexes to describe their particular catalytic activities and site-specificities with modified nucleosome substrates.
经典组蛋白去乙酰化酶 (HDACs) 是一种能够在组蛋白和其他蛋白质上水解性切割乙酰-Lys 的酶，并且在某些形式的癌症中作为既定的药物靶点。I 类 HDACs 1-3 通常存在于细胞内的多种蛋白质复合物中，在调节基因表达方面表现出不同的生物学功能。近年来，已经有可能对这些 HDAC 复合物的结构和酶学特性进行纯化和分析，包括 CoREST、MiDAC、NuRD、Sin3、SMRT、MIER 和 RERE。在这里，我们总结了实验确定的和/或计算预测的这些复合物的结构，以描述它们在修饰核小体底物时的特殊催化活性和特异性。
