The past decade has witnessed a significant growth in the identification of allosteric modulators of G protein-coupled receptors (GPCRs), i.e., ligands that interact with binding sites that are topographically distinct from the orthosteric site recognized by the receptor's endogenous agonist. Because of their ability to modulate receptor conformations in the presence of orthosteric ligand, allosteric modulators can "fine-tune" classical pharmacological responses. This is advantageous in terms of a potential for engendering greater GPCR subtype-selectivity, but represents a significant challenge for detecting and validating allosteric behaviors. Although allosteric sites need not have evolved to accommodate endogenous ligands, there are a number of examples of where such modulators have been shown to contribute to physiological or pathophysiological processes. Studies are also beginning to unravel the structural basis of allosteric modulation of GPCRs. It remains to be determined whether such modulation represents interactions within monomers versus across dimers.

中文翻译：

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G蛋白偶联受体的变构调节。

在过去的十年中，G蛋白偶联受体（GPCR）的变构调节剂的鉴定有了显着增长，即与与受体内源激动剂识别的正构位点在形貌上不同的结合位点相互作用的配体。由于它们在正构配体存在下调节受体构象的能力，变构调节剂可以“微调”经典药理反应。就产生更大的GPCR亚型选择性的潜力而言，这是有利的，但是对于检测和验证变构行为来说，这是一个重大挑战。尽管不需要变构位点来适应内源性配体，有许多例子表明这些调节剂有助于生理或病理生理过程。研究也开始揭示GPCR的变构调节的结构基础。尚待确定这种调节是否代表单体内与二聚体之间的相互作用。