Structural Genomics Consortium, University of Toronto, Toronto, Canada.
Department of Medical Biophysics, University of Toronto, Toronto, Canada.
Nat Struct Mol Biol. 2019 Oct;26(10):863-869. doi: 10.1038/s41594-019-0290-2. Epub 2019 Oct 3.
Chromatin regulatory proteins are increasingly recognized as potential new drug targets. Many of these proteins harbor one or more so called 'reader domains' that recognize covalent modifications of lysine and arginine residues, typically on histones, which mediate specific interactions within chromatin. Here we review recent progress in the discovery of drug-like small molecules that antagonize the function of methyl-lysine and methyl-arginine reader domains (Royal family, plant homeodomain (PHD) and WD40 domains) as well as the acyl-lysine-binding YEATS domain.
染色质调节蛋白正逐渐被视为潜在的新药靶标。这些蛋白质中许多都含有一个或多个所谓的“读取器结构域”，它们能识别赖氨酸和精氨酸残基的共价修饰，通常在组蛋白上，介导染色质内的特定相互作用。在这里，我们综述了最近在发现能拮抗甲基化赖氨酸和精氨酸读取器结构域（皇家结构域、植物同源结构域（PHD）和 WD40 结构域）以及酰化赖氨酸结合 YEATS 结构域功能的类药小分子方面的进展。
