PERIPHERAL BENZODIAZEPINE RECEPTOR STRUCTURAL BIOLOGY
外周苯二氮卓受体结构生物学
基本信息
- 批准号:6851390
- 负责人:
- 金额:$ 15.24万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2005
- 资助国家:美国
- 起止时间:2005-05-01 至 2007-04-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (provided by applicant): The human Peripheral Benzodiazepine Receptor (hPBR) is a highly hydrophobic, tryptophan-rich (7.7%) 18kDa protein consisting of 169 amino acids and five predicted transmembrane a-helices. hPBR is primarily localized within the mitochondrial outer membrane, where it is one component of the mitochondrial permeability transition pore complex. Although the primary cellular function of hPBR within the cell is not currently known, it has been implicated in a variety of cellular functions such as cellular proliferation and apoptosis, making hPBR a target for cancer therapy, hPBR has been cloned into an E. coli expression system, expression has been optimized, and reproducible high-level expression has been achieved. A robust two column purification method has been developed that enables the facile generation of multimilligram quantities of highly pure hPBR. The aims of this R21 application, submitted under Program Announcement PA-03-100, NIGMS Exploratory Studies for High Impact/High Risk Research, are to: 1) produce multi-milligram quantities of purified hPBR, and 2) conduct systematic three-dimensional crystallization experiments with hPBR and hPBR complexes. The goal of this proposal is to obtain crystals sufficient for structure determination of hPBR by x-ray crystallography. The longer-term goals of this effort are to conduct detailed structure-function studies of hPBR, to critically evaluate the utility of the hPBR structure for design of novel cancer drugs, and to extend our research to the structural biology of the mitochondrial permeability transition pore complex.
描述(申请人提供):人外周苯二氮卓类受体(HPBR)是一种高度疏水、富含色氨酸(7.7%)的18 kDa蛋白质,由169个氨基酸和5个预测的跨膜α-螺旋组成。HPBR主要定位于线粒体外膜,是线粒体通透性转换孔复合体的组成部分。虽然目前尚不清楚hPBR在细胞内的主要细胞功能,但它已参与细胞增殖和凋亡等多种细胞功能,使hPBR成为癌症治疗的靶点,hPBR已被克隆到大肠杆菌表达系统中,并进行了表达优化,实现了可重复的高水平表达。发展了一种可靠的双柱纯化方法,使高纯度的hPBR能够容易地产生多毫克数量的hPBR。根据项目公告PA-03-100,NIGMS高影响/高风险研究探索性研究提交的这份R21申请的目的是:1)生产多毫克量的纯化hPBR,以及2)对hPBR和hPBR复合体进行系统的三维结晶实验。这项建议的目标是获得足够的晶体,用于用X射线结晶学确定hPBR的结构。这项工作的长期目标是对hPBR进行详细的结构-功能研究,批判性地评估hPBR结构对设计新型抗癌药物的有效性,并将我们的研究扩展到线粒体通透性转换孔复合体的结构生物学。
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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Michael Wiener其他文献
Michael Wiener的其他文献
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{{ truncateString('Michael Wiener', 18)}}的其他基金
Structure and Function of the CaaX Protease Ste24p
CaaX 蛋白酶 Ste24p 的结构和功能
- 批准号:
8898849 - 财政年份:2014
- 资助金额:
$ 15.24万 - 项目类别:
Structure and Function of the CaaX Protease Ste24p
CaaX 蛋白酶 Ste24p 的结构和功能
- 批准号:
8610715 - 财政年份:2014
- 资助金额:
$ 15.24万 - 项目类别:
Structure and Function of the CaaX Protease Ste24p
CaaX 蛋白酶 Ste24p 的结构和功能
- 批准号:
9059738 - 财政年份:2014
- 资助金额:
$ 15.24万 - 项目类别:
Multi-level optimization of membrane proteins for crystallography
用于晶体学的膜蛋白的多级优化
- 批准号:
8152523 - 财政年份:2010
- 资助金额:
$ 15.24万 - 项目类别:
Structural Biology of Cancer Related Membrane Proteins Expressed in P. Pastoris
毕赤酵母表达的癌症相关膜蛋白的结构生物学
- 批准号:
7489827 - 财政年份:2007
- 资助金额:
$ 15.24万 - 项目类别:
Structural Biology of Cancer Related Membrane Proteins Expressed in P. Pastoris
毕赤酵母表达的癌症相关膜蛋白的结构生物学
- 批准号:
7683733 - 财政年份:2007
- 资助金额:
$ 15.24万 - 项目类别:
Structural Biology of Cancer Related Membrane Proteins Expressed in P. Pastoris
毕赤酵母表达的癌症相关膜蛋白的结构生物学
- 批准号:
7313169 - 财政年份:2007
- 资助金额:
$ 15.24万 - 项目类别:
Improved Methods for Membrane Protein Crystallization
膜蛋白结晶的改进方法
- 批准号:
7123041 - 财政年份:2005
- 资助金额:
$ 15.24万 - 项目类别:
Improved Methods for Membrane Protein Crystallization(RMI)
膜蛋白结晶 (RMI) 的改进方法
- 批准号:
7265251 - 财政年份:2005
- 资助金额:
$ 15.24万 - 项目类别:
Improved Methods: Membrane Protein Crystallization(RMI)
改进方法:膜蛋白结晶(RMI)
- 批准号:
7012589 - 财政年份:2005
- 资助金额:
$ 15.24万 - 项目类别:
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