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: 8362190
• 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: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362190
• 关键词: Bacteria; Binding; Collaborations; Evolution; Funding; GTP Cyclohydrolase; Glutathione; Grant; Heme; Hemeproteins; Homeostasis; Maps; Metal Binding Site; Metals; National Center for Research Resources; Nitric Oxide; Nitrosation; Oxidoreductase; Principal Investigator; Protein S; Proteins; Radiation; Research; Research Infrastructure; Resolution; Resources; Riboflavin; Signal Transduction; Signaling Protein; Site; Soluble Guanylate Cyclase; Source; Structure; Time; United States National Institutes of Health; base; cost; drug discovery; nitrophorin; structural biology; synchrotron radiation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 我们要求光束时间，以进一步几个项目。首先，我们正在研究亚硝化的血红素蛋白，包括亚硝酚和基于亚铁血红素的NO信号蛋白，特别是可溶性鸟苷环化酶(SGC)。第二，我们正在继续研究蛋白质S亚硝化，以及通过蛋白质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金属运输和动态平衡的蛋白质的研究，重点是CusF、SILF、CusB和CueO。最后，我们将与Matt Cordes合作，使用传递性同源性研究指导的结构确定来绘制Cro蛋白和Lipocalin的折叠进化图。水晶可用于所有项目。有些衍射率为1.0或更高。同步辐射用于(1)MAD结构测定，(2)提供足够的分辨率来确定准确的几何参数，如从平面性和金属结合位几何形状扭曲的血红素；(3)提供可变波长的X射线，用于明确识别结合的金属原子，并控制金属位和S-NO键的光还原。