从G蛋白偶联受体结构解析到合理药物设计。
From G Protein-coupled Receptor Structure Resolution to Rational Drug Design.
作者信息
Jazayeri Ali, Dias Joao M, Marshall Fiona H
机构信息
From Heptares Therapeutics Limited, BioPark, Broadwater Road, Welwyn Garden City AL7 3AX, United Kingdom
From Heptares Therapeutics Limited, BioPark, Broadwater Road, Welwyn Garden City AL7 3AX, United Kingdom.
出版信息
J Biol Chem. 2015 Aug 7;290(32):19489-95. doi: 10.1074/jbc.R115.668251. Epub 2015 Jun 22.
Abstract
A number of recent technical solutions have led to significant advances in G protein-coupled receptor (GPCR) structural biology. Apart from a detailed mechanistic view of receptor activation, the new structures have revealed novel ligand binding sites. Together, these insights provide avenues for rational drug design to modulate the activities of these important drug targets. The application of structural data to GPCR drug discovery ushers in an exciting era with the potential to improve existing drugs and discover new ones. In this review, we focus on technical solutions that have accelerated GPCR crystallography as well as some of the salient findings from structures that are relevant to drug discovery. Finally, we outline some of the approaches used in GPCR structure based drug design.
摘要
近期的一些技术解决方案推动了G蛋白偶联受体（GPCR）结构生物学的重大进展。除了对受体激活有详细的机制性认识外，新结构还揭示了新的配体结合位点。这些见解共同为合理药物设计提供了途径，以调节这些重要药物靶点的活性。将结构数据应用于GPCR药物发现开启了一个令人兴奋的时代，有望改进现有药物并发现新药物。在本综述中，我们重点关注加速GPCR晶体学研究的技术解决方案以及与药物发现相关的一些重要结构发现。最后，我们概述了基于GPCR结构的药物设计中使用的一些方法。
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本文引用的文献
1
Structural Insights into the Dynamic Process of β2-Adrenergic Receptor Signaling.β2-肾上腺素能受体信号转导动态过程的结构见解
Cell. 2015 May 21;161(5):1101-1111. doi: 10.1016/j.cell.2015.04.043. Epub 2015 May 14.
2
Structure of the Angiotensin receptor revealed by serial femtosecond crystallography.通过串联飞秒晶体学揭示的血管紧张素受体结构。
Cell. 2015 May 7;161(4):833-44. doi: 10.1016/j.cell.2015.04.011. Epub 2015 Apr 23.
3
Two disparate ligand-binding sites in the human P2Y1 receptor.人类P2Y1受体中的两个不同配体结合位点。
Nature. 2015 Apr 16;520(7547):317-21. doi: 10.1038/nature14287. Epub 2015 Mar 30.
4
Methodological advances: the unsung heroes of the GPCR structural revolution.方法学进展：GPCR 结构革命的无名英雄。
Nat Rev Mol Cell Biol. 2015 Feb;16(2):69-81. doi: 10.1038/nrm3933. Epub 2015 Jan 15.
5
Crystal structure of the human OX2 orexin receptor bound to the insomnia drug suvorexant.人源 OX2 食欲素受体与失眠药物苏沃雷生复合物的晶体结构
Nature. 2015 Mar 12;519(7542):247-50. doi: 10.1038/nature14035. Epub 2014 Dec 22.
6
Opportunities and challenges in the discovery of allosteric modulators of GPCRs for treating CNS disorders.发现用于治疗中枢神经系统疾病的GPCR变构调节剂的机遇与挑战。
Nat Rev Drug Discov. 2014 Sep;13(9):692-708. doi: 10.1038/nrd4308.
7
High-resolution structure of the human GPR40 receptor bound to allosteric agonist TAK-875.人源 GPR40 受体与变构激动剂 TAK-875 结合的高分辨率结构。
Nature. 2014 Sep 4;513(7516):124-7. doi: 10.1038/nature13494. Epub 2014 Jul 20.
8
Structure of class C GPCR metabotropic glutamate receptor 5 transmembrane domain.C 类 G 蛋白偶联受体代谢型谷氨酸受体 5 的跨膜结构域。
Nature. 2014 Jul 31;511(7511):557-62. doi: 10.1038/nature13396. Epub 2014 Jul 6.
9
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Trends Pharmacol Sci. 2014 Jul;35(7):308-16. doi: 10.1016/j.tips.2014.04.007. Epub 2014 May 28.
10
Agonist-bound structure of the human P2Y12 receptor.人源 P2Y12 受体激动剂结合结构。
Nature. 2014 May 1;509(7498):119-22. doi: 10.1038/nature13288.
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