Herold J Martin, Ingerman Lindsey A, Gao Cen, Frye Stephen V
Center for Integrated Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, Division of Medicinal Chemistry and Natural Products, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Curr Chem Genomics. 2011;5:51-61. doi: 10.2174/1875397301005010051. Epub 2011 Aug 22.
The recognition of methyl-lysine and -arginine residues on both histone and other proteins by specific "reader" elements is important for chromatin regulation, gene expression, and control of cell-cycle progression. Recently the crucial role of these reader proteins in cancer development and dedifferentiation has emerged, owing to the increased interest among the scientific community. The methyl-lysine and -arginine readers are a large and very diverse set of effector proteins and targeting them with small molecule probes in drug discovery will inevitably require a detailed understanding of their structural biology and mechanism of binding. In the following review, the critical elements of methyl-lysine and -arginine recognition will be summarized with respect to each protein family and initial results in assay development, probe design, and drug discovery will be highlighted.
特定的“读取器”元件对组蛋白和其他蛋白质上甲基化赖氨酸和精氨酸残基的识别对于染色质调控、基因表达以及细胞周期进程的控制至关重要。近来，由于科学界兴趣日增，这些读取器蛋白在癌症发展和去分化过程中的关键作用逐渐显现。甲基化赖氨酸和精氨酸读取器是一大类且非常多样的效应蛋白，在药物研发中用小分子探针靶向它们将不可避免地需要对其结构生物学和结合机制有详细了解。在接下来的综述中，将针对每个蛋白质家族总结甲基化赖氨酸和精氨酸识别的关键要素，并重点介绍在检测方法开发、探针设计和药物研发方面的初步成果。
