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。 我们正在申请进一步的四个项目。 首先，我们正在继续我们的研究亚硝基血红素蛋白，包括nitrophorins和其他血红素为基础的NO信号蛋白。 第二，我们已经进行了广泛的研究蛋白质S-亚硝化NO信号，包括S-NO的形成（硫氧还蛋白，肌红蛋白），和谷胱甘肽S-亚硝化的蛋白质GSNO还原酶的控制。 这些研究包括药物发现部分。 第三，我们正在研究S. coleicolor，特别是GTP环化水解酶II家族。 第四，我们正在研究几种蛋白质中的反应中间体，包括多铜氧化酶CueO。同步辐射需要：（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。

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.