Heptares Therapeutics Ltd, BioPark, Broadwater Road, Welwyn Garden City, AL7 3AX, UK.
Division of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
Trends Pharmacol Sci. 2014 Jan;35(1):12-22. doi: 10.1016/j.tips.2013.11.001. Epub 2013 Dec 18.
The secretin-like (class B) family of G protein-coupled receptors (GPCRs) are key players in hormonal homeostasis and are interesting drug targets for the treatment of several metabolic disorders (such as type 2 diabetes, osteoporosis, and obesity) and nervous system diseases (such as migraine, anxiety, and depression). The recently solved crystal structures of the transmembrane domains of the human glucagon receptor and human corticotropin-releasing factor receptor 1 have opened up new opportunities to study the structure and function of class B GPCRs. The current review shows how these structures offer more detailed explanations to previous biochemical and pharmacological studies of class B GPCRs, and provides new insights into their interactions with ligands.
分泌素样(B 类)家族的 G 蛋白偶联受体(GPCRs)是激素内稳态的关键参与者,也是治疗多种代谢紊乱(如 2 型糖尿病、骨质疏松症和肥胖症)和神经系统疾病(如偏头痛、焦虑症和抑郁症)的有趣药物靶点。最近解决的人类胰高血糖素受体和人类促肾上腺皮质激素释放因子受体 1 的跨膜结构域的晶体结构为研究 B 类 GPCR 的结构和功能开辟了新的机会。本综述展示了这些结构如何为 B 类 GPCR 的先前生化和药理学研究提供更详细的解释,并为它们与配体的相互作用提供了新的见解。