STRUCTURE DETERMINATION OF RV2996C/NADH, AND RV2513

RV2996C/NADH 和 RV2513 的结构测定

• 批准号: 7598267
• 负责人: MANG YU
• 金额: $ 0.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7598267
• 关键词: 2-hydroxyacid dehydrogenase; Adult; Binding; Binding Sites; Biochemistry; Chemicals; Computer Retrieval of Information on Scientific Projects Database; Disease; Enzymes; Foundations; Funding; GTP Binding; Goals; Grant; Growth; Human; Institution; Isomerism; Lead; Life Cycle Stages; Metabolism; Mycobacterium tuberculosis; NADH; PAWR protein; Phosphoglycerate dehydrogenase; Physiology; Protein Structure Initiative; Proteins; Research; Research Personnel; Resources; Respiration; Serine; Serum; Source; Structure; Tuberculosis; United States National Institutes of Health; base; design; drug development; inhibitor/antagonist; killings; pathogen; structural genomics; tuberculosis drugs

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.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 结核分枝杆菌（TB）是一种人类病原体，导致该疾病，结核病，每年造成超过200万人。它是世界上成年人的第一杀手。作为由NIH？S蛋白结构倡议资助的TB结构基因组学（TBSGC）的一部分，我们的主要目标是确定独特和/或功能上重要的TB蛋白，以帮助了解TB生理学并帮助建立抗TB药物开发的基础。我们最近结晶了两个新的结核病靶蛋白。 （1）RV2996C，D-3-磷酸甘油酸脱氢酶或血清是中间代谢和TB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-羟基酸脱氢酶的特征。可以使用类似的结构，但其NADH界形式尚未揭幕。其结构将有助于了解结核病中丝氨酸合成中的生物化学，并在设计抑制剂方面提供化学基础。 （2）RV2513，一种对TB生长必不可少的假设蛋白。这将导致一个对TB的生命周期至关重要的新结构。新结构可能包含有关此新目标功能的重要线索。