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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们正在请求光束时间来进一步推进四个项目。首先，我们继续研究亚硝化的亚铁血红素蛋白，包括亚硝酚类和其他以亚铁血红素为基础的NO信号蛋白。其次，我们对蛋白质S亚硝化在NO信号转导中的作用进行了广泛的研究，包括蛋白质S亚硝化(硫氧还蛋白，肌红蛋白)，以及蛋白质GSNO还原酶对谷胱甘肽S亚硝化的调控。这些研究包括药物发现部分。第三，我们正在研究与金黄色葡萄球菌核黄素合成有关的蛋白质，特别是GTP环水解酶II家族。第四，我们正在寻找几种蛋白质中的反应中间体，包括多铜氧化酶CueO。同步辐射对于以下方面是需要的：(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，定义从平面性到血红素的扭曲，模拟多种构象；以及确定活性晶体中冷冻捕获的中间体的结构；(3)可变的X射线波长可以用于最大限度地减少铁-血红素中心的光还原。

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.