Nuffield Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7LD, UK.
FEBS Lett. 2012 Aug 14;586(17):2692-704. doi: 10.1016/j.febslet.2012.04.045. Epub 2012 May 3.
ε-N-acetylation of lysine residues (K(ac)) is one of the most abundant post-translation modifications (PTMs) in the human proteome. In the nucleus, acetylation of histones has been linked to transcriptional activation of genes but the functional consequences of most acetylation events and proteins recruited to these sites remains largely unknown. Bromodomains (BRDs) are small helical interaction modules that specifically recognize acetylation sites in proteins. BRDs have recently emerged as interesting targets for the development of specific protein interaction inhibitors, enabling a novel exiting strategy for the development of new therapies. This review provides an overview over sequence requirements of BRDs, known substrates and the structural mechanisms of specific K(ac) recognition.
赖氨酸残基的 ε-N-乙酰化（K(ac)）是人类蛋白质组中最丰富的翻译后修饰（PTM）之一。在核内，组蛋白的乙酰化与基因的转录激活有关，但大多数乙酰化事件的功能后果和被招募到这些位点的蛋白质仍然知之甚少。溴结构域（BRDs）是特异性识别蛋白质中乙酰化位点的小螺旋相互作用模块。BRDs 最近作为特异性蛋白质相互作用抑制剂开发的有趣靶点出现，为新疗法的开发提供了一种新的策略。这篇综述概述了 BRDs 的序列要求、已知的底物以及特异性 K(ac)识别的结构机制。
