• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

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。

相似文献

1
X-Ray Crystallographic Studies for Revealing Binding Sites of General Anesthetics in Pentameric Ligand-Gated Ion Channels.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
Methods Enzymol. 2018;603:21-47. doi: 10.1016/bs.mie.2018.01.017. Epub 2018 Mar 24.
2
Solution NMR Studies of Anesthetic Interactions with Ion Channels.麻醉剂与离子通道相互作用的溶液核磁共振研究。
Methods Enzymol. 2018;603:49-66. doi: 10.1016/bs.mie.2018.01.018. Epub 2018 Mar 8.
3
Structural Analysis of Anesthetics in Complex with Soluble Proteins.麻醉剂与可溶性蛋白质复合物的结构分析
Methods Enzymol. 2018;603:3-20. doi: 10.1016/bs.mie.2018.01.016. Epub 2018 Mar 2.
4
X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel.与五聚体配体门控离子通道结合的全身麻醉剂的 X 射线结构。
Nature. 2011 Jan 20;469(7330):428-31. doi: 10.1038/nature09647.
5
Structure of the pentameric ligand-gated ion channel GLIC bound with anesthetic ketamine.五聚体配体门控离子通道 GLIC 与麻醉剂氯胺酮结合的结构。
Structure. 2012 Sep 5;20(9):1463-9. doi: 10.1016/j.str.2012.08.009.
6
Direct Pore Binding as a Mechanism for Isoflurane Inhibition of the Pentameric Ligand-gated Ion Channel ELIC.直接孔道结合作为异氟烷抑制五聚体配体门控离子通道ELIC的一种机制。
Sci Rep. 2015 Sep 8;5:13833. doi: 10.1038/srep13833.
7
Crystallographic studies of pharmacological sites in pentameric ligand-gated ion channels.五聚体配体门控离子通道中药理学位点的晶体学研究。
Biochim Biophys Acta. 2015 Mar;1850(3):511-23. doi: 10.1016/j.bbagen.2014.05.007. Epub 2014 May 14.
8
Structural Basis for a Bimodal Allosteric Mechanism of General Anesthetic Modulation in Pentameric Ligand-Gated Ion Channels.五聚体配体门控离子通道中全身麻醉剂调制的双模态变构机制的结构基础。
Cell Rep. 2018 Apr 24;23(4):993-1004. doi: 10.1016/j.celrep.2018.03.108.
9
Study, by use of coarse-grained models, of the functionally crucial residues and allosteric pathway of anesthetic regulation of the Gloeobacter violaceus ligand-gated ion channel.利用粗粒度模型对蓝细菌紫膜配体门控离子通道麻醉调节的功能关键残基和变构途径进行研究。
Eur Biophys J. 2014 Dec;43(12):623-30. doi: 10.1007/s00249-014-0992-7. Epub 2014 Nov 4.
10
A membrane-embedded pathway delivers general anesthetics to two interacting binding sites in the ion channel.一条嵌入膜的途径将全身麻醉剂传递至离子通道中的两个相互作用的结合位点。
J Biol Chem. 2017 Jun 9;292(23):9480-9492. doi: 10.1074/jbc.M117.780197. Epub 2017 Apr 18.

引用本文的文献

1
Alkylphenol inverse agonists of HCN1 gating: H-bond propensity, ring saturation and adduct geometry differentially determine efficacy and potency.HCN1 门控的烷基酚反向激动剂：氢键倾向、环饱和度和加合物几何形状差异决定效力和效价。
Biochem Pharmacol. 2019 May;163:493-508. doi: 10.1016/j.bcp.2019.02.013. Epub 2019 Feb 13.

本文引用的文献

1
Crystal Structures of Human GlyRα3 Bound to Ivermectin.与伊维菌素结合的人甘氨酸受体α3的晶体结构
Structure. 2017 Jun 6;25(6):945-950.e2. doi: 10.1016/j.str.2017.04.007. Epub 2017 May 4.
2
Identification of a pre-active conformation of a pentameric channel receptor.五聚体通道受体预激活构象的鉴定。
Elife. 2017 Mar 15;6:e23955. doi: 10.7554/eLife.23955.
3
Crystal structure and dynamics of a lipid-induced potential desensitized-state of a pentameric ligand-gated channel.五聚体配体门控通道脂质诱导潜在脱敏状态的晶体结构与动力学
Elife. 2017 Mar 6;6:e23886. doi: 10.7554/eLife.23886.
4
Crystal structures of human glycine receptor α3 bound to a novel class of analgesic potentiators.人源甘氨酸受体α3与新型类镇痛药增效剂结合的晶体结构。
Nat Struct Mol Biol. 2017 Feb;24(2):108-113. doi: 10.1038/nsmb.3329. Epub 2016 Dec 19.
5
Barbiturates Bind in the GLIC Ion Channel Pore and Cause Inhibition by Stabilizing a Closed State.巴比妥类药物结合于GLIC离子通道孔内，并通过稳定关闭状态引起抑制作用。
J Biol Chem. 2017 Feb 3;292(5):1550-1558. doi: 10.1074/jbc.M116.766964. Epub 2016 Dec 16.
6
Structural Basis of Alcohol Inhibition of the Pentameric Ligand-Gated Ion Channel ELIC.酒精对五聚体配体门控离子通道ELIC抑制作用的结构基础
Structure. 2017 Jan 3;25(1):180-187. doi: 10.1016/j.str.2016.11.007. Epub 2016 Dec 1.
7
Fluorine-19 NMR and computational quantification of isoflurane binding to the voltage-gated sodium channel NaChBac.氟-19核磁共振及异氟烷与电压门控钠通道NaChBac结合的计算定量分析
Proc Natl Acad Sci U S A. 2016 Nov 29;113(48):13762-13767. doi: 10.1073/pnas.1609939113. Epub 2016 Nov 15.
8
Processing of X-ray diffraction data collected in oscillation mode.振荡模式下收集的X射线衍射数据的处理。
Methods Enzymol. 1997;276:307-26. doi: 10.1016/S0076-6879(97)76066-X.
9
X-ray structure of the human α4β2 nicotinic receptor.人类α4β2烟碱型受体的X射线结构。
Nature. 2016 Oct 20;538(7625):411-415. doi: 10.1038/nature19785. Epub 2016 Oct 3.
10
Shedding Light on Anesthetic Mechanisms: Application of Photoaffinity Ligands.揭示麻醉机制：光亲和配体的应用
Anesth Analg. 2016 Nov;123(5):1253-1262. doi: 10.1213/ANE.0000000000001365.