STRUCTURE DETERMINATION OF RV2996C/NADH, AND RV2513

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。子项目及 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（Mycobacterium tuberculosis，TB）是引起结核病的人类病原体，每年导致超过200万人死亡。 它是世界上成人的头号传染性杀手。 作为由NIH蛋白质结构计划资助的结核病结构基因组学联盟（TBSGC）的一部分，我们的主要目标是确定独特和/或功能重要的结核病蛋白质，以帮助了解结核病生理学，并帮助建立抗结核病药物开发的基础。 我们最近结晶了两种新的结核病靶蛋白。 （一） Rv 2996 C是一种D-3-磷酸甘油酸脱氢酶，或serA，是TB中间代谢和呼吸的关键酶。 它包含ATP/GTP结合位点基序A（P环）、D-异构体特异性2-羟基酸脱氢酶NAD结合特征和D-异构体特异性2-羟基酸脱氢酶特征。 类似的结构是可用的，但其NADH结合形式尚未公布。 其结构将有助于了解结核病丝氨酸合成的生物化学过程，并为设计抑制剂提供化学基础。 (2)Rv 2513是一种保守的假设蛋白，对结核菌的生长至关重要。 这将导致一个对结核病生命周期至关重要的新结构。 这种新结构可能包含了了解这种新靶点功能的重要线索。

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(TB) is a human pathogen causing the disease, tuberculosis, killing over 2 million people per year. It is the No. 1 infectious killer of adults in the world. As part of the TB Structural Genomics Consortium (TBSGC) funded by the NIH¿s Protein Structure Initiative, our main goal is to determine unique and/or functionally important TB proteins to help understand TB physiology and to help establish the foundation of anti-TB drug development. We recently crystallized two new TB target proteins. (1) Rv2996C, a D-3-phosphoglycerate dehydrogenase, or serA, is a key enzyme in intermediary metabolism and respiration of TB. It contains ATP/GTP-binding site motif A (P-loop), D-isomer specific 2-hydroxyacid dehydrogenases NAD-binding signature and D-isomer specific 2-hydroxyacid dehydrogenases signature. Similar structures are available but its NADH bound form has not been unveiled. Structure of this will help understand the biochemistry in Serine synthesis in TB and provide chemical basis in designing inhibitors. (2) Rv2513, a conserved hypothetical protein essential to TB¿s growth. This will lead to a new structure crucial to TB¿s life cycle. The new structure may contain important clue to the function of this new target.