CRYSTALLOGRAPHY OF PROLINE CATABOLIC ENZYMES, PHOSPHATASES, AND PARVALBUMINS

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。子项目和 研究者（PI）可能从另一个NIH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 研究中心，而研究中心不一定是研究者所在的机构。 本计画的目标是确定脯氨酸分解代谢酵素、磷酸酶及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（P5 CDH）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、超氧化物生成、细胞凋亡和癌症中起重要作用。脯氨酸代谢的先天性缺陷导致I型高脯氨酸血症（PRODH）和II型高脯氨酸血症（P5 CDH）。 在某些细菌中，这两种酶融合成双功能酶，脯氨酸利用A（PutA）。 因此，PutAs作为研究基板沟道的系统。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P5 CDH酶，PutA结构域和全长PutA。 磷酸酶催化磷酰基从磷酸单酯转移到水。 研究中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。 Parvalbumins（PV）是小EF-手型钙结合蛋白，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，这些小清蛋白跨越了广泛的金属结合亲和力：禽胸腺激素（ATH）和大鼠β-PV和禽小清蛋白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.