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用于揭示全身麻醉药在五聚体配体门控离子通道中结合位点的X射线晶体学研究

X-Ray Crystallographic Studies for Revealing Binding Sites of General Anesthetics in Pentameric Ligand-Gated Ion Channels.

作者信息

Chen Qiang, Xu Yan, Tang Pei

机构信息

University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.

University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.

出版信息

Methods Enzymol. 2018;603:21-47. doi: 10.1016/bs.mie.2018.01.017. Epub 2018 Mar 24.

DOI:10.1016/bs.mie.2018.01.017
PMID:29673527
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6490682/
Abstract

X-ray crystallography is a powerful tool in structural biology and can offer insight into structured-based understanding of general anesthetic action on various relevant molecular targets, including pentameric ligand-gated ion channels (pLGICs). In this chapter, we outline the procedures for expression and purification of pLGICs. Optimization of crystallization conditions, especially to achieve high-resolution structures of pLGICs bound with general anesthetics, is also presented. Case studies of pLGICs bound with the volatile general anesthetic isoflurane, 2-bromoethanol, and the intravenous general anesthetic ketamine are revisited.

摘要

X射线晶体学是结构生物学中的一种强大工具，能够深入了解基于结构的全身麻醉药对各种相关分子靶点（包括五聚体配体门控离子通道，pLGICs）的作用机制。在本章中，我们概述了pLGICs的表达和纯化程序。还介绍了结晶条件的优化，特别是为了获得与全身麻醉药结合的pLGICs的高分辨率结构。重新审视了pLGICs与挥发性全身麻醉药异氟烷、2-溴乙醇以及静脉全身麻醉药氯胺酮结合的案例研究。

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