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.

该副本是利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，这不一定是调查员的机构。 该项目的目的是确定脯氨酸分解代谢酶，磷酸酶和白蛋白酶的晶体结构。 脯氨酸分解代谢酶脯氨酸脱氢酶（PODH）和吡咯氨酸-5-羧酸甲酯脱氢酶（P5CDH）催化脯氨酸的4电子氧化为谷氨酸。这些酶在细胞氧化还原控制，超氧化物，凋亡和癌症中起重要作用。脯氨酸分解代谢的天生错误导致高丙二元血症I型（prodh）和II型（P5CDH）。 在某些细菌中，将两种酶融合到双功能酶，脯氨酸利用A（puta）中。 因此，PUTA是研究底物通道的系统。该项目的一部分的目的是为几种脯氨酸分解代谢酶（包括单功能PODH和P5CDH酶，PUTA域和全长PUTAS）收集高分辨率单晶X射线衍射数据。 磷酸酶催化磷酸基从磷酸化的转移到水。 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与底物和底物类似物复合的这些磷酸酶的晶体结构，以阐明底物特异性的基础。 白蛋白（PVS）是主要在钙缓冲中起作用的小型EF手钙结合蛋白。该项目的这一部分的目的是阐明三种代表性白细胞蛋白的不同金属离子结合特征的结构基础，它们跨越了广泛的金属结合亲和力：鸟类胸腺激素（ATH）和大鼠β-PV和鸟鸟Parvalbumin 3。