CRYSTALLOGRAPHY OF PROLINE CATABOLIC ENZYMES, PHOSPHATASES, AND PARVALBUMINS

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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.