CRYSTALLOGRAPHY OF PROLINE CATABOLIC ENZYMES, PHOSPHATASES, AND PARVALBUMINS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 该项目的目标是确定脯氨酸分解代谢酶、磷酸酶和小白蛋白的晶体结构。Pro分解代谢酶(PROH)和5-吡咯烷-5-羧酸脱氢酶(P5CDH)催化Pro 4电子氧化为谷氨酸。这些酶在细胞氧化还原控制、超氧化物生成、细胞凋亡和癌症中发挥重要作用。先天的脯氨酸分解代谢错误会导致I型(PROH)和II型(P5CDH)的高脯氨酸血症。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)。因此，PUTA可作为研究衬底沟道的系统。该项目的一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，包括单功能的PROSH和P5CDH酶、PUTA结构域和全长PUTA。磷酸酶催化磷酸单酯向水中转移一个磷酰基。正在研究的磷酸酶包括组氨酸酸性磷酸酶(HAPS)和C类酸性磷酸酶(CCAPS)。我们的主要目标是确定这些与底物和底物类似物络合的磷酸酶的晶体结构，以阐明底物专一性的基础。细小蛋白(PV)是一种小的EF手性钙结合蛋白，主要起钙缓冲作用。这部分项目的目的是阐明三种具有代表性的小白蛋白与金属离子结合的不同特征的结构基础，这三种小白蛋白具有广泛的金属结合亲和力：鸟类胸腺激素(ATH)和大鼠β-PV和鸟类小白蛋白3。

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.