Chemical basis for the recognition of trimethyllysine by epigenetic reader proteins.
Chemical basis for the recognition of trimethyllysine by epigenetic reader proteins.
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表观遗传阅读器蛋白识别三甲基赖氨酸的化学基础。
DOI：
10.1038/ncomms9911
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发表时间：
2015-11-18
影响因子：
16.6
通讯作者：
Mecinović J
中科院分区：
文献类型：
--
作者：
Kamps JJ;Huang J;Poater J;Xu C;Pieters BJ;Dong A;Min J;Sherman W;Beuming T;Matthias Bickelhaupt F;Li H;Mecinović J
大量结构多样的表观遗传阅读器蛋白特异性识别组蛋白上的甲基化赖氨酸残基。在这里，我们描述了比较热力学，结构和计算研究识别带正电荷的天然三甲基赖氨酸及其中性类似物的读者蛋白质。这项工作提供了实验和理论证据，即阅读器蛋白主要通过有利的阳离子-π相互作用和释放高能水分子的组合来识别三甲基赖氨酸，所述高能水分子占据与三甲基赖氨酸侧链缔合的阅读器蛋白的芳香笼。这些结果具有合理的药物设计的影响，具体针对芳香笼读者的三甲基赖氨酸。 一组结构多样的表观遗传阅读器蛋白可以识别组蛋白上的甲基化赖氨酸残基。在这里，作者表明，三甲基赖氨酸的识别是通过有利的阳离子-π相互作用和释放占据阅读器蛋白芳香笼的水分子的组合发生的。
A large number of structurally diverse epigenetic reader proteins specifically recognize methylated lysine residues on histone proteins. Here we describe comparative thermodynamic, structural and computational studies on recognition of the positively charged natural trimethyllysine and its neutral analogues by reader proteins. This work provides experimental and theoretical evidence that reader proteins predominantly recognize trimethyllysine via a combination of favourable cation–π interactions and the release of the high-energy water molecules that occupy the aromatic cage of reader proteins on the association with the trimethyllysine side chain. These results have implications in rational drug design by specifically targeting the aromatic cage of readers of trimethyllysine. A structurally diverse set of epigenetic reader proteins can recognize methylated lysine residues on histones. Here the authors show that recognition of trimethyllysine occurs through a combination of favourable cation–π interactions and the release of water molecules occupying the aromatic cages of reader proteins.