Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina, USA.
Br J Pharmacol. 2012 Mar;165(6):1659-1669. doi: 10.1111/j.1476-5381.2011.01749.x.
Seven transmembrane receptors (7TMRs) are nature's prototype allosteric proteins made to bind molecules at one location to subsequently change their shape to affect the binding of another molecule at another location. This paper attempts to describe the divergent 7TMR behaviours (i.e. third party allostery, receptor oligomerization, biased agonism) observed in pharmacology in terms of a homogeneous group of allosteric behaviours. By considering the bodies involved as a vector defined by a modulator, conduit and guest, these activities can all be described by a simple model of functional allostery made up of the Ehlert allosteric model and the Black/Leff operational model. It will be shown how this model yields parameters that can be used to characterize the activity of any ligand or protein producing effect through allosteric interaction with a 7TMR.
七次跨膜受体（7TMRs）是自然界的变构蛋白原型，旨在结合一个位置的分子，随后改变其形状以影响另一个位置的另一个分子的结合。本文试图根据一组同质的变构行为来描述在药理学中观察到的不同的 7TMR 行为（即第三方变构作用、受体寡聚化、偏向激动作用）。通过将参与的主体视为由调节剂、导管和客体定义的向量，可以使用由 Ehlert 变构模型和 Black/Leff 操作模型组成的简单功能变构模型来描述这些活性。将展示如何使用该模型生成可用于表征任何通过与 7TMR 进行变构相互作用产生效应的配体或蛋白质的活性的参数。
