KATching-Up on Small Molecule Modulators of Lysine Acetyltransferases
KATching-Up on Small Molecule Modulators of Lysine Acetyltransferases
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DOI：
10.1021/acs.jmedchem.5b01502
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发表时间：
2016-02-25
影响因子：
7.3
通讯作者：
Jung, Manfred
中科院分区：
文献类型：
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作者：
Simon, Roman P.;Robaa, Dina;Jung, Manfred
赖氨酸的可逆乙酰化是表征最好的表观遗传修饰之一。它参与许多关键的生理和病理过程已被记录在许多研究中。赖氨酸脱乙酰酶（KDAC）和乙酰转移酶（KAT）维持组蛋白以及许多其他蛋白质的乙酰化平衡。除了乙酰化，其他酰基也可逆地安装在蛋白质中赖氨酸的侧链上。由于它们参与疾病，KDAC和KAT被认为是有希望的药物靶点，事实上，对于KDAC，现在有五种抑制剂被批准用于人类。虽然有类似水平的证据表明KAT作为药物靶点的潜力，但没有抑制剂在临床试验中。在这里，我们回顾了KAT在疾病病理学中的不同作用的证据，提供了结构特征和可用调节剂的概述，包括那些针对KAT的溴结构域的调节剂，并提出了展望。
The reversible acetylation of lysines is one of the best characterized epigenetic modifications. Its involvement in many key physiological and pathological processes has been documented in numerous studies. Lysine deacetylases (KDACs) and acetyltransferases (KATs) maintain the acetylation equilibrium at histones but also many other proteins. Besides acetylation, also other acyl groups are reversibly installed at the side chain of lysines in proteins. Because of their involvement in disease, KDACs and KATs were proposed to be promising drug targets, and for KDACs, indeed, five inhibitors are now approved for human use. While there is a similar level of evidence for the potential of KATs as drug targets, no inhibitor is in clinical trials. Here, we review the evidence for the diverse roles of KATs in disease pathology, provide an overview of structural features and the available modulators, including those targeting the bromodomains of KATs, and present an outlook.