Unraveling allosteric landscapes of allosterome with ASD
Unraveling allosteric landscapes of allosterome with ASD
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揭示 ASD 的变构组景观
DOI：
10.1093/nar/gkz958
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发表时间：
2020-01-08
影响因子：
14.9
通讯作者：
Zhang, Jian
中科院分区：
文献类型：
--
作者：
Liu, Xinyi;Lu, Shaoyong;Zhang, Jian
变构调节是微调蛋白质功能最直接和有效的方式之一；它是由配体在与正构位点在拓扑结构上不同的变构位点结合所诱导的。变构数据库（ASD，可在http://mdl.shsmu.edu.cn/ASD在线获取）是十年前开发的，旨在提供与变构调节相关的全面信息。近年来，变构调节在生物学研究、生物工程和药物研发中受到了极大关注，从而出现了作为变构组的整个变构格局。为了从变构组的角度促进研究，在2019年的ASD中，整理了如下新特性：（i）为变构药物研发储存了超过10000个人类蛋白质的潜在变构位点；（ii）构建了7种人类变构组图谱，包括蛋白酶和离子通道图谱，以揭示家族内的变构进化；（iii）从33种癌症类型的患者样本中收集了1312个变构位点的体细胞错义突变；（iv）从变构位点提取了1493个药效团用于调节剂筛选。在过去的十年中，ASD已成为研究变构调节的核心资源，并将在未来的靶点识别和变构药物研发中发挥更重要的作用。
Allosteric regulation is one of the most direct and efficient ways to fine-tune protein function; it is induced by the binding of a ligand at an allosteric site that is topographically distinct from an orthosteric site. The Allosteric Database (ASD, available online at http://mdl.shsmu.edu.cn/ASD) was developed ten years ago to provide comprehensive information related to allosteric regulation. In recent years, allosteric regulation has received great attention in biological research, bioengineering, and drug discovery, leading to the emergence of entire allosteric landscapes as allosteromes. To facilitate research from the perspective of the allosterome, in ASD 2019, novel features were curated as follows: (i) >10 000 potential allosteric sites of human proteins were deposited for allosteric drug discovery; (ii) 7 human allosterome maps, including protease and ion channel maps, were built to reveal allosteric evolution within families; (iii) 1312 somatic missense mutations at allosteric sites were collected from patient samples from 33 cancer types and (iv) 1493 pharmacophores extracted from allosteric sites were provided for modulator screening. Over the past ten years, the ASD has become a central resource for studying allosteric regulation and will play more important roles in both target identification and allosteric drug discovery in the future.