X-RAY STRUCTURES OF PENTAMERIC ION CHANNELS IN THE ABSENCE AND PRESENCE OF ANEST
不存在和存在 Anest 时五聚体离子通道的 X 射线结构
基本信息
- 批准号:8362296
- 负责人:
- 金额:$ 0.14万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-03-01 至 2012-02-29
- 项目状态:已结题
- 来源:
- 关键词:AffinityAnestheticsBindingBinding SitesBreathingBromidesCationsChloride IonChloridesComplexDataDoseFamilyFundingGated Ion ChannelGeneral AnesthesiaGeneral anesthetic drugsGrantHalothaneHomologous GeneIntravenous AnestheticsIon ChannelKetamineLigandsMolecularNational Center for Research ResourcesPrincipal InvestigatorProteinsRadiationResearchResearch InfrastructureResolutionResourcesRoentgen RaysSourceStructureSulfurThiopentalUnited States National Institutes of Healthbasebeamlinecostmolecular sizenovelprotein functionstructural biology
项目摘要
This subproject is one of many research subprojects utilizing the resources
provided by a Center grant funded by NIH/NCRR. Primary support for the subproject
and the subproject's principal investigator may have been provided by other sources,
including other NIH sources. The Total Cost listed for the subproject likely
represents the estimated amount of Center infrastructure utilized by the subproject,
not direct funding provided by the NCRR grant to the subproject or subproject staff.
The molecular mechanism of general anesthesia remains an enigma. Although a superfamily of pentameric ligand gated ion channels (pLGICs) has been identified as putative targets of general anesthetics, the lack of high-resolution structures of these pLGICs hinders the understanding where anesthetic binding sites are in these proteins and how anesthetic bindings impact on protein functions. An exciting platform for getting the answers has recently emerged as the x-ray structures of two bacterial homologs to the pLGIC family, GLIC and ELIC, were solved with resolutions of 2.9 and 3.3 ¿. As cation channels, GLIC and ELIC can be crystallized in the open- and close-channel states, respectively. Similar to mammalian pLGIC cation channels, cation conductance of GLIC could be inhibited by a variety of anesthetics at subclinical doses. Here we propose to co-crystallize GLIC and ELIC with general anesthetics. No anesthetic has been crystallized with any pLGICs in the past. The x-ray structures of GLIC- and ELIC-anesthetics complexes will provide novel structural basis to explain the functional impact of general anesthetics to the pLGICs. Inhaled anesthetic halothane and intravenous anesthetics thiopental and ketamine are chosen for the study. We have crystallized GLIC and ELIC in the absence and presence of anesthetics. Our preliminary data show that the resolutions up to 2.7 ¿ and 2.9 ¿ have been achieved for GLIC in the presence of thiopental and ketamine. Despite tangible protein resolutions, to define precise anesthetic binding sites in the proteins remains challenging because of small anesthetic molecular sizes and relatively low anesthetic binding affinities (~100 ?M). Thus, we request to use specific beamlines that provide high sensitivity and resolution to bromide, sulfur, and possibly chloride atoms. These atoms are contained in the selected anesthetics and can serve as marks for anesthetics in the proteinanesthetic complexes.
这个子项目是利用这些资源的众多研究子项目之一
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('PEI TANG', 18)}}的其他基金
New Glycinergic Modulators as Potent Painkillers without Negative Psychoactive Effects - Supplement
新型甘氨酸调节剂作为有效的止痛药,没有负面的精神影响 - 补充
- 批准号:
10054996 - 财政年份:2019
- 资助金额:
$ 0.14万 - 项目类别:
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9915878 - 财政年份:2018
- 资助金额:
$ 0.14万 - 项目类别:
Alpha7 Nicotinic Receptor: Structures and Coupling with Intracellular Proteins
Alpha7 烟碱受体:结构及其与细胞内蛋白质的偶联
- 批准号:
10169782 - 财政年份:2018
- 资助金额:
$ 0.14万 - 项目类别:
Alpha7 Nicotinic Receptor: Structures and Coupling with Intracellular Proteins
Alpha7 烟碱受体:结构及其与细胞内蛋白质的偶联
- 批准号:
10393547 - 财政年份:2018
- 资助金额:
$ 0.14万 - 项目类别:
LARGE SCALE MD SIMULATIONS OF ANESTHETIC EFFECTS ON ION CHANNELS
离子通道麻醉效果的大规模 MD 模拟
- 批准号:
8364249 - 财政年份:2011
- 资助金额:
$ 0.14万 - 项目类别:
ANESTHETIC EFFECTS ON ION CHANNEL STRUCTURES & DYNAMICS
对离子通道结构的麻醉作用
- 批准号:
8127591 - 财政年份:2010
- 资助金额:
$ 0.14万 - 项目类别:
LARGE SCALE MD SIMULATIONS OF ANESTHETIC EFFECTS ON ION CHANNELS
离子通道麻醉效果的大规模 MD 模拟
- 批准号:
8171827 - 财政年份:2010
- 资助金额:
$ 0.14万 - 项目类别:
X-RAY STRUCTURES OF PENTAMERIC ION CHANNELS IN THE ABSENCE AND PRESENCE OF ANEST
不存在和存在 Anest 时五聚体离子通道的 X 射线结构
- 批准号:
8170297 - 财政年份:2010
- 资助金额:
$ 0.14万 - 项目类别:
LARGE SCALE MD SIMULATIONS OF ANESTHETIC EFFECTS ON ION CHANNELS
离子通道麻醉效果的大规模 MD 模拟
- 批准号:
7956089 - 财政年份:2009
- 资助金额:
$ 0.14万 - 项目类别:
LARGE SCALE MD SIMULATIONS OF ANESTHETIC EFFECTS ON ION CHANNELS
离子通道麻醉效果的大规模 MD 模拟
- 批准号:
7723136 - 财政年份:2008
- 资助金额:
$ 0.14万 - 项目类别:
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