MYCOBACTERIAL TUBERCULOSIS PROTEASOME

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 结核分枝杆菌(Mtb)持续感染约20亿人。确定微生物用来抵抗宿主免疫反应的途径可能会为预防或治疗结核病提供新的靶点。Darwin等人(2003)已经确定了几个插入蛋白酶体相关基因的Mtb突变株，它们需要抵抗一氧化氮和其他活性氮中间体(RNI)。为了理解和解释分枝杆菌蛋白酶体是如何抵抗氧化或亚硝化应激的，需要确定含有抑制剂的Mtb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-EM图像，但我们需要残基水平(至少3埃)的X射线蛋白质结构来了解细节。我们已经结晶了Mtb蛋白，我们希望使用同步加速器光束线来收集衍射数据。

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.