Jazayeri Ali, Dias Joao M, Marshall Fiona H
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.
J Biol Chem. 2015 Aug 7;290(32):19489-95. doi: 10.1074/jbc.R115.668251. Epub 2015 Jun 22.
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.
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。
