PROTEINS INVOLVED WITH NITRIC OXIDE SIGNALING, RIBOFLAVIN SYNTHESIS AND COPPER H

与一氧化氮信号传导、核黄素合成和铜 H 相关的蛋白质

• 批准号: 7954309
• 负责人: SUE L ROBERTS
• 金额: $ 0.21万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954309
• 关键词: Computer Retrieval of Information on Scientific Projects Database; Copper; Family; Freezing; Funding; GTP Cyclohydrolase II; Glutathione; Grant; Heme; Heme Iron; Hemeproteins; Institution; Modeling; Molecular Conformation; Myoglobin; Nitric Oxide; Nitrosation; Oxidases; Oxidoreductase; Proteins; Reaction; Research; Research Personnel; Resolution; Resources; Riboflavin; SKIL gene; Signal Transduction; Signaling Protein; Source; Structure; Thioredoxin; Time; United States National Institutes of Health; adduct; base; drug discovery; structural biology; synchrotron radiation

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. We are requesting beam time to further four projects. First we are continuing our studies on nitrosylated heme proteins, including the nitrophorins and other heme-based NO signaling proteins. Second, we have undertaken a wide-ranging study of protein S-nitrosation in NO signaling, including S-NO formation (thioredoxin, myoglobin), and control of glutathione S-nitrosation by the protein GSNO reductase. These studies include a drug discovery component. Third, we are investigating proteins involved in riboflavin synthesis in S. coleicolor, particularly the GTP cyclohydrolase II family. Fourth, we are pursuing reaction intermediates in several proteins, including the multicopper oxidase CueO. Synchrotron radiation is needed for: (1) MAD structure determination; (2) Sufficient resolution to determine accurate geometry of SNO adducts, define heme distortion from planarity, model multiple conformations; and determine the structure of freeze-trapped intermediates in active crystals; (3) Variable x-ray wavelengths can be used to minimize photoreduction of iron-heme centers.

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。子项目和 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。 我们正在请求时间来推进四个项目。 首先，我们继续研究亚硝基化血红素蛋白，包括硝基蛋白和其他基于血红素的 NO 信号蛋白。 其次，我们对 NO 信号传导中的蛋白质 S-亚硝化进行了广泛的研究，包括 S-NO 形成（硫氧还蛋白、肌红蛋白）以及蛋白质 GSNO 还原酶对谷胱甘肽 S-亚硝化的控制。 这些研究包括药物发现部分。 第三，我们正在研究 S. coleicolor 中参与核黄素合成的蛋白质，特别是 GTP 环水解酶 II 家族。 第四，我们正在寻找多种蛋白质的反应中间体，包括多铜氧化酶 CueO。需要同步辐射的有： (1) MAD结构测定； (2) 足够的分辨率来确定 SNO 加合物的精确几何形状、定义平面性的血红素畸变、模拟多种构象；并确定活性晶体中冷冻捕获的中间体的结构； (3) 可变的 X 射线波长可用于最大限度地减少铁血红素中心的光还原。