全身麻醉药在蛋白模型和离子通道的分子靶位及变构调节机制

The allosteric regulation of general anesthetics on protein models and ion channels as well as their target sites

背景全麻药地氟醚和丙泊酚与原核细胞膜中的五聚体配体门控型离子通道（pentameric ligand-gated ion channels，pLGICs）复合体的结晶结构，为研究全麻药与大脑pLGICs变构调节部位之间的相互作用提供了一个新奇的结构框架，使全麻药作用机制的变构调节学说有了许多新的实验支持。目的概述全麻药作用的分子靶位及变构调节机制。内容简介“变构”（“allosteric”）一词的由来及发展，阐述麻醉药在蛋白模型和离子通道的分子靶位及调节机制，提出麻醉药在pLGICs的分子靶位有两个关键结合位点，分别通过影响受体的亲和力或直接对受体发挥作用，而影响受体亲和力的主要分子机制是变构调节。趋势随着科技的发展及许多新技术和新方法的应用，全麻药在中枢神经系统的各种分子靶位及调节机制将逐步得到破解。

Background The complex crystal structure of general anesthetics desflurane or propofol and pentameric ligandgated ion channels （pLGICs） in prokaryotic cell membrane, provides a novel structural framework for the design of general anesthetics and of allosteric modulators of brain pLGICs and gets many new experiment support about the allosteric regulation theory. Objective To summarize the general anesthetics molecular sites and allosteric regulation mechanism. Content This paper introduces the origin and development of the word ＂al]osteric＂, expounds the molecular sites and modulate mechanisms of general anesthetics action on protein models and ion channels, and proposes two key binding sites of anesthetics in pLGICs mediating receptor affinity and direct activation receptor respectively. But the allosteric regulation is the main mechanism of mediating receptor affinity. Trend With the development of science and technology and application of many new technology and new method, it will gradually be understanded that various kinds of molecular sites of general anesthetics in the central nervous system and regulation mechanism.