组蛋白去乙酰化酶的结构及应用  

Structure and Catalytic Mechanisms of Histone Deacetylases

作　　者：曹端方 杨娜[1] 

机构地区：[1]中国科学院生物物理研究所生物大分子国家重点实验室,北京100101

出　　处：《生物化学与生物物理进展》2015年第11期978-993,共16页Progress In Biochemistry and Biophysics

基　　金：国家重点基础研究发展计划(973)资助项目(2015CB856202);国家自然科学基金资助项目(31430018);卫生部重大新药创制专项(2014ZX09507002)资助~~

摘　　要：组蛋白赖氨酸乙酰化是目前研究最为广泛和深入的组蛋白翻译后修饰之一,在染色质重塑和基因表达调控等方面发挥重要作用,这种修饰在体内受到组蛋白乙酰化酶和去乙酰化酶的高度动态调控.除了以组蛋白为底物外,组蛋白去乙酰化酶还可以催化多种非组蛋白的去乙酰化,参与多种生命过程的调节.本文围绕四类人源组蛋白去乙酰化酶,综述了其分类依据、结构与功能特点、催化反应的分子机制,以及针对这些组蛋白去乙酰化酶的抑制剂和激动剂的开发和应用等方面的研究进展.Lysine acetylation is one of the most widely studied post-translational modifications of histones. It plays important roles in the regulation of chromatin remodeling and gene expression. This modification is dynamically regulated in vivo by histone acetyltransferases and deacetylases. Besides histone substrates, many histone deacetylases can also catalyze deacetylation of non-histone substrates, and participate in the regulation of various biological pathways. In this review, we discuss the classification, structure, function, and catalytic mechanisms of the four known classes of human histone deacetylases, as well as the progress in the development and application of small molecule inhibitors and activators of these deacetylases.

关 键 词：组蛋白乙酰化修饰 组蛋白去乙酰化酶 SIRTUIN 结构与功能 催化机制 抑制剂 激动剂 

分 类 号：Q6[生物学—生物物理学]