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Insight into SUCNR1 (GPR91) structure and function.
Pharmacology & Therapeutics ( IF 12.0 ) Pub Date : 2016-01-26 , DOI: 10.1016/j.pharmthera.2016.01.008
Julie Gilissen 1 , François Jouret 2 , Bernard Pirotte 3 , Julien Hanson 1
Affiliation  

SUCNR1 (or GPR91) belongs to the family of G protein-coupled receptors (GPCR), which represents the largest group of membrane proteins in human genome. The majority of marketed drugs targets GPCRs, directly or indirectly. SUCNR1 has been classified as an orphan receptor until a landmark study paired it with succinate, a citric acid cycle intermediate. According to the current paradigm, succinate triggers SUCNR1 signaling pathways to indicate local stress that may affect cellular metabolism. SUCNR1 implication has been well documented in renin-induced hypertension, ischemia/reperfusion injury, inflammation and immune response, platelet aggregation and retinal angiogenesis. In addition, the SUCNR1-induced increase of blood pressure may contribute to diabetic nephropathy or cardiac hypertrophy. The understanding of SUCNR1 activation, signaling pathways and functions remains largely elusive, which calls for deeper investigations. SUCNR1 shows a high potential as an innovative drug target and is probably an important regulator of basic physiology. In order to achieve the full characterization of this receptor, more specific pharmacological tools such as small-molecules modulators will represent an important asset. In this review, we describe the structural features of SUCNR1, its current ligands and putative binding pocket. We give an exhaustive overview of the known and hypothetical signaling partners of the receptor in different in vitro and in vivo systems. The link between SUCNR1 intracellular pathways and its pathophysiological roles are also extensively discussed.

中文翻译:

深入了解SUCNR1(GPR91)的结构和功能。

SUCNR1(或GPR91)属于G蛋白偶联受体(GPCR)家族,代表人类基因组中最大的膜蛋白组。市场上出售的大多数药物都直接或间接靶向GPCR。SUCNR1被归类为孤儿受体,直到一项具有里程碑意义的研究将其与琥珀酸(柠檬酸循环中间体)配对。根据当前的范例,琥珀酸触发SUCNR1信号传导途径来指示可能影响细胞代谢的局部应激。SUCNR1的意义已在肾素诱导的高血压,局部缺血/再灌注损伤,炎症和免疫反应,血小板聚集和视网膜血管生成中得到了充分的证明。此外,SUCNR1引起的血压升高可能导致糖尿病性肾病或心脏肥大。了解SUCNR1激活,信号通路和功能仍然很难捉摸,这需要更深入的研究。SUCNR1显示出作为创新药物靶标的巨大潜力,并且可能是基本生理学的重要调节剂。为了完全表征该受体,更具体的药理学工具(例如小分子调节剂)将成为重要资产。在这篇综述中,我们描述了SUCNR1的结构特征,其当前的配体和推定的结合口袋。我们给出了在不同的体内和体外系统中受体的已知和假设的信号伴侣的详尽概述。SUCNR1细胞内途径之间的联系及其病理生理作用也进行了广泛的讨论。SUCNR1显示出作为创新药物靶标的巨大潜力,并且可能是基本生理学的重要调节剂。为了完全表征该受体,更具体的药理学工具(例如小分子调节剂)将成为重要资产。在这篇综述中,我们描述了SUCNR1的结构特征,其当前的配体和推定的结合口袋。我们详尽地概述了受体在不同的体外和体内系统中的已知和假设的信号伴侣。SUCNR1细胞内途径之间的联系及其病理生理作用也进行了广泛的讨论。SUCNR1显示出作为创新药物靶标的巨大潜力,并且可能是基本生理学的重要调节剂。为了完全表征该受体,更具体的药理学工具(例如小分子调节剂)将成为重要资产。在这篇综述中,我们描述了SUCNR1的结构特征,其当前的配体和推定的结合口袋。我们给出了在不同的体内和体外系统中受体的已知和假设的信号伴侣的详尽概述。SUCNR1细胞内途径之间的联系及其病理生理作用也进行了广泛的讨论。更具体的药理工具,例如小分子调节剂将代表重要的资产。在这篇综述中,我们描述了SUCNR1的结构特征,其当前的配体和推定的结合口袋。我们详尽地概述了受体在不同的体外和体内系统中的已知和假设的信号伴侣。SUCNR1细胞内途径之间的联系及其病理生理作用也进行了广泛的讨论。更具体的药理工具,例如小分子调节剂将代表重要的资产。在这篇综述中,我们描述了SUCNR1的结构特征,其当前的配体和推定的结合口袋。我们详尽地概述了受体在不同的体外和体内系统中的已知和假设的信号伴侣。SUCNR1细胞内途径之间的联系及其病理生理作用也进行了广泛的讨论。
更新日期:2016-01-22
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