STRUCTURAL BIOLOGY OF SELECTED TARGETS FROM M TUBERCULOSIS FOR THE DESIGN OF NO

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。我们从结核分枝杆菌中选择了近140个靶基因进行克隆、表达和晶体结构测定。这些靶点要么是功能未知的基因产物，要么是解毒或氨基酸合成中几个重要途径的酶活性。迄今为止，已经确定了7个晶体结构，并且许多靶点已经被克隆、表达和结晶。结构工作正在继续对先前确定的晶体结构，目的是阐明设计有效抑制剂的详细酶促机制。该项目需要筛选通常大量的晶体，MAD或SAD定相和高分辨率数据收集，以可视化底物或抑制剂结合的细节。

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. We have selected almost 140 target genes from Mycobacterium tuberculosis for cloning, expression and crystal structure determination. The targets are either gene products with an unknown function or are enzymatic activities from several essential pathways involved in detoxification or amino acid synthesis. 7 crystal structures have been determined to date and a number of targets haven been cloned, expressed and crystallized. Structural work is continuing on the previously determined crystal structures with the goal of elucidating the detailed enzymatic mechanism for the design of effective inhibitors. The project requires the screening of typically large numbers of crystals, MAD or SAD phasing and high-resolution data collection to visualize the details of substrate or inhibitor binding.