CRYSTALLOGRAPHY OF PROLINE CATABOLIC ENZYMES, PHOSPHATASES, AND PARVALBUMINS

脯氨酸分解酶、磷酸酶和小清蛋白的晶体学

• 批准号: 8169278
• 负责人: JOHN J TANNER
• 金额: $ 0.7万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169278
• 关键词: Acid Phosphatase; Affinity; Apoptosis; Bacteria; Binding; Birds; Buffers; Calcium; Calcium-Binding Proteins; Catabolism; Complex; Computer Retrieval of Information on Scientific Projects Database; Crystallography; Data; Disease; EF Hand Motifs; Electrons; Enzymes; Funding; Generations; Glutamates; Goals; Grant; Histidine; Inborn Genetic Diseases; Institution; Length; Malignant Neoplasms; Metal Ion Binding; Metals; Oxidation-Reduction; Oxidoreductase; Parvalbumins; Phosphoric Monoester Hydrolases; Play; Proline; Proline Dehydrogenase; Rattus; Research; Research Personnel; Resolution; Resources; Role; Source; Structure; Substrate Specificity; Superoxides; System; United States National Institutes of Health; Water; X ray diffraction analysis; X-Ray Diffraction; analog; avian thymic hormone; base; carboxylate; oxidation; phosphomonoester; protein function; pyrroline

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. The goal of this project is determine crystal structures of proline catabolic enzymes, phosphatases, and parvalbumins. The proline catabolic enzymes proline dehydrogenase (PRODH) and pyrroline-5-carboxylate dehydrogenase (P5CDH) catalyze the 4-electron oxidation of proline to glutamate. These enzymes play important roles in cellular redox control, superoxide generation, apoptosis, and cancer. Inborn errors of proline catabolism result in hyperprolinemia disorders Type I (PRODH) and Type II (P5CDH). In some bacteria, the two enzymes are fused into the bifunctional enzyme, proline utilization A (PutA). PutAs thus serve as systems for studying substrate channeling. The goal of part of the project is to collect high resolution single crystal X-ray diffraction data for several proline catabolic enzymes, including monofunctional PRODH and P5CDH enzymes, PutA domains, and full-length PutAs. Phosphatases catalyze the transfer of a phosphoryl group from phosphomonoesters to water. Phosphatases under study include histidine acid phosphatases (HAPs) and class C acid phosphatases (CCAPs). Our main goal is to determine crystal structures of these phosphatases complexed with substrates and substrate analogues to elucidate the basis for substrate specificity. Parvalbumins (PVs) are small EF-hand calcium-binding proteins that function mainly in calcium buffering. The goal of this part of the project is to elucidate the structural basis for the different metal ion-binding signatures of three representative parvalbumins that span a wide range of metal binding affinity: avian thymic hormone (ATH) and rat beta-PV and avian parvalbumin 3.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 该项目的目标是确定脯氨酸分解代谢酶、磷酸酶和小清蛋白的晶体结构。 脯氨酸分解代谢酶脯氨酸脱氢酶 (PRODH) 和吡咯啉-5-羧酸脱氢酶 (P5CDH) 催化脯氨酸向谷氨酸的 4 电子氧化。这些酶在细胞氧化还原控制、超氧化物生成、细胞凋亡和癌症中发挥重要作用。脯氨酸分解代谢的先天性错误会导致 I 型 (PRODH) 和 II 型 (P5CDH) 高脯氨酸血症疾病。 在一些细菌中，这两种酶融合成双功能酶，即脯氨酸利用 A (PutA)。 PutAs 因此可作为研究底物沟道的系统。该项目的部分目标是收集几种脯氨酸分解代谢酶的高分辨率单晶 X 射线衍射数据，包括单功能 PRODH 和 P5CDH 酶、PutA 结构域和全长 PutAs。 磷酸酶催化磷酰基从磷酸单酯转移到水。 正在研究的磷酸酶包括组氨酸酸性磷酸酶 (HAP) 和 C 类酸性磷酸酶 (CCAP)。 我们的主要目标是确定这些磷酸酶与底物和底物类似物复合的晶体结构，以阐明底物特异性的基础。 小清蛋白 (PV) 是一种小的 EF 手钙结合蛋白，主要起钙缓冲作用。该项目这一部分的目标是阐明三种代表性小清蛋白的不同金属离子结合特征的结构基础，这些小清蛋白具有广泛的金属结合亲和力：禽类胸腺激素 (ATH) 和大鼠 β-PV 以及禽类小清蛋白 3。