A pharmacological organization of G protein-coupled receptors.
A pharmacological organization of G protein-coupled receptors.
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DOI：
10.1038/nmeth.2324
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发表时间：
2013-02
期刊：
影响因子：
48
通讯作者：
Shoichet, Brian K.
中科院分区：
文献类型：
--
作者：
Lin, Henry;Sassano, Maria F.;Roth, Bryan L.;Shoichet, Brian K.
蛋白质分类通常利用结构、序列或功能相似性。在此我们介绍一种正交方法，该方法通过配体相似性对蛋白质进行分类，这里重点关注A类G蛋白偶联受体（GPCR）蛋白家族。将基于配体的树状图与基于序列的树状图进行比较，我们寻找了那些在序列上关联较远但在配体相似性上是近邻的GPCR实例。对预测能连接其中三对新组合的化合物进行实验测试，证实了预测的关联性，效力范围从低纳摩尔到低微摩尔不等。然后我们通过配体相似性确定了数百种与GPCR密切相关的非GPCR，包括从CXCR2趋化因子受体到酪蛋白激酶I，从大麻素受体到环氧化物水解酶2，以及从α2肾上腺素能受体到磷脂酶D。这些也通过实验得到了证实。这些靶点之间的配体相似性可能反映了分子信号传导在时间域上的一种化学整合。
Protein classification typically uses structural, sequence, or functional similarity. Here we introduce an orthogonal method that organizes proteins by ligand similarity, focusing here on the class A G protein-coupled receptor (GPCR) protein family. Comparing a ligand-based dendogram to a sequence-based one, we sought examples of GPCRs that were distantly linked by sequence but neighbors by ligand similarity. Experimental testing of compounds predicted to link three of these new pairs confirmed the predicted association, with potencies ranging from the low-nanomolar to low-micromolar. We then identified hundreds of non-GPCRs closely related to GPCRs by ligand similarity, including the CXCR2 chemokine receptor to Casein kinase I, the cannabinoid receptors to epoxide hydrolase 2, and the α2 adrenergic receptor to phospholipase D. These, too, were confirmed experimentally. Ligand similarities among these targets may reflect a chemical integration in the time domain of molecular signaling.
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影响因子：
14.8
作者：
Scott, Sarah A.;Selvy, Paige E.;Buck, Jason R.;Cho, Hyekyung P.;Criswell, Tracy L.;Thomas, Ashley L.;Armstrong, Michelle D.;Arteaga, Carlos L.;Lindsley, Craig W.;Brown, H. Alex
通讯作者：
Brown, H. Alex
影响因子：
4.2
作者：
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通讯作者：
Aube, Jeffrey
影响因子：
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作者：
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通讯作者：
Marks DS
影响因子：
6.8
作者：
Hopkins, AL;Mason, JS;Overington, JP
通讯作者：
Overington, JP
影响因子：
5.6
作者：
Irwin JJ;Sterling T;Mysinger MM;Bolstad ES;Coleman RG
通讯作者：
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