MYCOBACTERIAL TUBERCULOSIS PROTEASOME

结核分枝杆菌蛋白酶体

• 批准号: 7957285
• 负责人: Jianfei Jiang
• 金额: $ 0.74万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7957285
• 关键词: Computer Retrieval of Information on Scientific Projects Database; Crystallography; Data; Funding; Genes; Grant; Image; Immune response; Institution; Light; Microbe; Mycobacterium tuberculosis; Nitric Oxide; Nitrogen; Pathway interactions; Prevention; Proteins; Research; Research Personnel; Resources; Source; Structure; Synchrotrons; Tuberculosis; United States National Institutes of Health; beamline; inhibitor/antagonist; multicatalytic endopeptidase complex; mutant; mycobacterial; nitrosative stress; protein structure; tuberculosis treatment

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Mycobacterium tuberculosis (Mtb) persistently infects about two billion people. The identification of pathways used by the microbe to resist eleimination by the host immune response may suggest new targets for prevention or treatment of tuberculosis. Several mutants of Mtb with the insertions in proteasome-associated genes have been identified by Darwin, etc. (2003) that are required to resist nitric oxide and other reactive nitrogen intermediates (RNI). To understand and interpret how mycobacterial proteasome severs as a defense agaist oxidative or nitrosative stress, the crystal structures of Mtb proteins with the inhibitors are deserved to be determinated. Although we have obtained cryo-EM images of Mtb proteasome in 20 angstroms, we need the x-ray protein structures at the residue level (at least 3 angstroms) for the details. We have already crystallized the Mtb proteins and we are expecting to use synchrotron beamlines to collect the diffraction data.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 结核分枝杆菌（Mtb）持续感染约20亿人。鉴定微生物抵抗宿主免疫反应清除的途径可能为预防或治疗结核病提供新的靶点。达尔文等（2003）已经鉴定了几种在蛋白酶体相关基因中插入的Mtb突变体，其是抵抗一氧化氮和其它活性氮中间体（RNI）所需的。为了理解和解释结核分枝杆菌蛋白酶体是如何抵抗氧化或亚硝化应激的，有必要确定具有抑制剂的结核分枝杆菌蛋白的晶体结构。 虽然我们已经获得了20埃的Mtb蛋白酶体的冷冻电镜图像，但我们需要残留水平（至少3埃）的X射线蛋白质结构的细节。 我们已经使结核分枝杆菌蛋白质结晶，我们期望使用同步加速器光束线来收集衍射数据。