PROTEIN CRYSTAL STRUCTURE DETERMINATIONS RELATED TO NITRIC OXIDE SIGNALING AND O

与一氧化氮信号传导和 O 相关的蛋白质晶体结构测定

• 批准号: 7954493
• 负责人: SUE L ROBERTS
• 金额: $ 0.06万
• 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/7954493
• 关键词: Bacteria; Binding; Collaborations; Computer Retrieval of Information on Scientific Projects Database; Evolution; Funding; GTP Cyclohydrolase; Glutathione; Grant; Heme; Hemeproteins; Homeostasis; Institution; Maps; Metal Binding Site; Metals; Nitric Oxide; Nitrosation; Oxidoreductase; Proteins; Research; Research Personnel; Resolution; Resources; Riboflavin; Signal Transduction; Signaling Protein; Site; Soluble Guanylate Cyclase; Source; Structure; Time; United States National Institutes of Health; 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 request beam time to further several projects. First, we are studying nitrosylated heme proteins, including nitrophorins and heme-based NO signaling proteins, particularly soluble guanylate cyclase (sGC). Second, we are continuing studies of protein S-nitrosation, and control of glutathione S-nitrosation by the protein GSNO reductase. The GSNOR studies include a drug discovery component. Third, we are investigating proteins involved in riboflavin synthesis, particularly the GTP cyclohydrolases. Fourth, we are expanding studies of proteins involved in metal transport and homeostasis in bacteria, focusing on cusF, silF, cusB, and cueO. Finally, we will, in collaboration with Matt Cordes, use structure determinations guided by transitive homology studies to map fold evolution of Cro proteins and lipocalins. Crystals are available for all projects. Some diffract to 1.0 ¿ or better. Synchrotron radiation is needed for (1) MAD structure determination, (2) to provide sufficient resolution to determine accurate geometrical parameters such as heme distortion from planarity and metal binding site geometries; (3) to provide variable wavelength x-rays for unambiguous identification of bound metal atoms and to control photoreduction of metal sites and S-NO bonds.

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来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们要求有更多的时间来进一步进行几个项目。 首先，我们正在研究亚硝基化血红素蛋白，包括nitrophorins和血红素为基础的NO信号蛋白，特别是可溶性鸟苷酸环化酶（sGC）。 其次，我们正在继续研究蛋白质S-亚硝化，并通过蛋白质GSNO还原酶控制谷胱甘肽S-亚硝化。 GSNOR研究包括药物发现部分。 第三，我们正在研究与核黄素合成有关的蛋白质，特别是GTP环水解酶。 第四，我们正在扩大对参与细菌中金属转运和稳态的蛋白质的研究，重点是cusF，silF，cusB和cueO。 最后，我们将与Matt Cordes合作，使用传递同源性研究指导的结构测定来绘制Cro蛋白和脂质运载蛋白的折叠进化。 水晶可用于所有项目。 有些人的行为达到1.0或更好。 需要同步辐射用于（1）MAD结构测定，（2）提供足够的分辨率以确定精确的几何参数，例如来自平面性和金属结合位点几何形状的血红素失真;（3）提供可变波长的X射线以用于明确识别结合的金属原子并控制金属位点和S-NO键的光还原。