ASD v3.0: unraveling allosteric regulation with structural mechanisms and biological networks.
ASD v3.0: unraveling allosteric regulation with structural mechanisms and biological networks.
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ASD v3.0：通过结构机制和生物网络阐明变构调节。
DOI：
10.1093/nar/gkv902
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发表时间：
2016-01-04
影响因子：
14.9
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Shen Q;Wang G;Li S;Liu X;Lu S;Chen Z;Song K;Yan J;Geng L;Huang Z;Huang W;Chen G;Zhang J
变构调节是调节蛋白质功能的最直接和有效的方式，它是由配体在地形上与正构位点不同的一个位点的结合诱导的。变构数据库（ASD，可在线访问http://mdl.shsmu.edu.cn/ASD）的开发旨在提供有关变构调节的全面信息。随着数据的增加，与变构有关的基本问题目前受到越来越多的关注，从单个蛋白质变构变化的机制到细胞内互联网络变化的整体影响。因此，在这个更新版本中增加了以下新特征：(i)通过比较结合调节剂前后的位点结构，阐明了1600多种变构作用的结构机制；（ii）鉴定了261个变构网络，揭示了单个蛋白质的变构作用如何传播并影响下游蛋白质；（iii）完全构建了两个最大的人类变构体，蛋白激酶和gpcr；（iv）网络界面和数据组织完全重新设计，以实现高效访问。此外，在这次更新中，变构数据有了很大的扩展。这些更新有助于促进变构机制、动态网络和药物发现的研究。
Allosteric regulation, the most direct and efficient way of regulating protein function, is induced by the binding of a ligand at one site that is topographically distinct from an orthosteric site. Allosteric Database (ASD, available online at http://mdl.shsmu.edu.cn/ASD) has been developed to provide comprehensive information featuring allosteric regulation. With increasing data, fundamental questions pertaining to allostery are currently receiving more attention from the mechanism of allosteric changes in an individual protein to the entire effect of the changes in the interconnected network in the cell. Thus, the following novel features were added to this updated version: (i) structural mechanisms of more than 1600 allosteric actions were elucidated by a comparison of site structures before and after the binding of an modulator; (ii) 261 allosteric networks were identified to unveil how the allosteric action in a single protein would propagate to affect downstream proteins; (iii) two of the largest human allosteromes, protein kinases and GPCRs, were thoroughly constructed; and (iv) web interface and data organization were completely redesigned for efficient access. In addition, allosteric data have largely expanded in this update. These updates are useful for facilitating the investigation of allosteric mechanisms, dynamic networks and drug discoveries.