Sanchez Roberto, Zhou Ming-Ming
Mount Sinai School of Medicine, Department of Structural and Chemical Biology, New York, NY 10029, USA.
Curr Opin Drug Discov Devel. 2009 Sep;12(5):659-65.
The acetylation of histone lysine is central to providing the dynamic regulation of chromatin-based gene transcription. The bromodomain (BRD), which is the conserved structural module in chromatin-associated proteins and histone acetyltranferases, is the sole protein domain known to recognize acetyl-lysine residues on proteins. Structural analyses of the recognition of lysine-acetylated peptides derived from histones and cellular proteins by BRDs have provided new insights into the differences between and unifying features of the selectivity that BRDs exhibit in binding biological ligands. Recent research has highlighted the importance of BRD/acetyl-lysine binding in orchestrating molecular interactions in chromatin biology and regulating gene transcription. These studies suggest that modulating BRD/acetyl-lysine interactions with small molecules may provide new opportunities for the control of gene expression in human health and disease.
组蛋白赖氨酸的乙酰化对于基于染色质的基因转录的动态调控至关重要。溴结构域（BRD）是染色质相关蛋白和组蛋白乙酰转移酶中保守的结构模块，是已知唯一能识别蛋白质上乙酰赖氨酸残基的蛋白结构域。对BRD识别源自组蛋白和细胞蛋白的赖氨酸乙酰化肽的结构分析，为BRD在结合生物配体时所表现出的选择性的差异和统一特征提供了新的见解。最近的研究强调了BRD/乙酰赖氨酸结合在协调染色质生物学中的分子相互作用和调节基因转录方面的重要性。这些研究表明，用小分子调节BRD/乙酰赖氨酸相互作用可能为控制人类健康和疾病中的基因表达提供新的机会。
