...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular informatics >Finding Inspiration in the Protein Data Bank to Chemically Antagonize Readers of the Histone Code
【24h】

Finding Inspiration in the Protein Data Bank to Chemically Antagonize Readers of the Histone Code

机译：在蛋白质数据库中寻找启发，以化学拮抗组蛋白密码的读者

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Members of the Royal family of proteins are readers of the histone code that contain aromatic cages capable of recognizing specific sequences and lysine methyla-tion states on histone tails. These binding modules play a key role in epigenetic signalling, and are part of a larger group of epigenetic targets that are becoming increasingly attractive for drug discovery. In the current study, pharma-cophore representations of the aromatic cages forming the methyl-lysine (Me-Lys) recognition site were used to search the Protein Data Bank (PDB) for ligand binding pockets possessing similar chemical and geometrical features in unrelated proteins. The small molecules bound to these sites were then extracted from the PDB, and clustered based on fragments binding to the aromatic cages. The compounds collected are numerous and structurally diverse, but point to a limited set of preferred chemotypes; these include quaternary ammonium, sulfonium, and primary, secondary and tertiary amine moieties, as well as aromatic, aliphatic or orthogonal rings, and bicyclic systems. The chemical tool-kit identified can be used to design antagonists of the Royal family and related proteins.
机译：皇家蛋白质家族的成员是组蛋白密码的阅读者，组蛋白密码包含能够识别组蛋白尾巴上特定序列和赖氨酸甲基化状态的芳香笼。这些结合模块在表观遗传信号传导中起关键作用，并且是表观遗传靶标中越来越多的一部分，这些靶标对药物发现越来越有吸引力。在当前的研究中，形成甲基赖氨酸（Me-Lys）识别位点的芳族笼的药效学表示法用于在蛋白质数据库（PDB）中搜索配体结合口袋，该口袋在无关蛋白质中具有相似的化学和几何特征。然后从PDB中提取与这些位点结合的小分子，并根据与芳香族笼子结合的片段进行聚类。收集到的化合物数量众多，结构上也各不相同，但指出的是有限的一组优选化学型。这些包括季铵，sulf和伯，仲和叔胺部分，以及芳族，脂族或正交环和双环系统。鉴定出的化学工具包可用于设计王室和相关蛋白质的拮抗剂。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号