Structural Basis for Allosteric Modulation of Class B G Protein-Coupled Receptors.
Structural Basis for Allosteric Modulation of Class B G Protein-Coupled Receptors.
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DOI：
10.1146/annurev-pharmtox-010919-023301
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发表时间：
2020-01
影响因子：
12.5
通讯作者：
D. Wootten;L. Miller
中科院分区：
文献类型：
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作者：
D. Wootten;L. Miller
最近我们对B类G蛋白偶联受体（gpcr）结构和功能的理解取得了进展，为靶向开发变构调节剂提供了多种机会。鉴于这些受体在对各种天然激动剂配体的反应中发出的多效信号模式，调节剂有可能塑造反应，以满足不同患者群体的不同需求。在这篇综述中，我们提供了关于GPCRs家族与其他超家族的不同之处的见解，正构激动剂如何结合和激活这些受体，变构调节剂与这些靶点的不同区域相互作用的潜力，以及内源性蛋白质对这些受体药理学的变构影响，所有这些都是开发新疗法时重要的考虑因素。《药理学和毒理学年度评论》第60卷的最终在线出版日期预计为2020年1月6日。修订后的估计数请参阅http://www.annualreviews.org/page/journal/pubdates。
Recent advances in our understanding of the structure and function of class B G protein-coupled receptors (GPCRs) provide multiple opportunities for targeted development of allosteric modulators. Given the pleiotropic signaling patterns emanating from these receptors in response to a variety of natural agonist ligands, modulators have the potential to sculpt the responses to meet distinct needs of different groups of patients. In this review, we provide insights into how this family of GPCRs differs from the rest of the superfamily, how orthosteric agonists bind and activate these receptors, the potential for allosteric modulators to interact with various regions of these targets, and the allosteric influence of endogenous proteins on the pharmacology of these receptors, all of which are important considerations when developing new therapies. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 60 is January 6, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.