STRUCTURE DETERMINATION OF RPRP(90 231)

RPRP的结构确定(90 231)

• 批准号: 6347905
• 负责人: HE LIU
• 金额: $ 0.61万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6347905
• 关键词: AIDS; biomedical resource; immunology; infection; inflammation; lymphatic system; technology /technique; virus

We have determined the structure of a recombinant fragment (90-231) of Syrian hamster PrP gene product using 3 dimensional heteronuclear NMR. Prions are infectious particles that cause fatal neurodegenerative disorders in humans and animals, such as scrapie in sheep, mad cow disease, and kuru, Cruetzfeld-Jakob, Gerstmann-Staussler-Scheinker disease, and fatal familial insomnia in humans. The diseases' process is unusual in that it is propagated by the change of the conformation of prion proteins from the normal cellular form (PrPc, predominantly alpha helical) to the abnormal aggregated beta-sheet form (PrP Scrapie). The determination of Prp structure is important for both the understanding of prion diseases, and drug design. We use heteronuclear NMR techniques and the graphical NMR software Sparky to make the resonance assignment and NOE cross peak assignment for the determination of the PrP(90-231) structure. The structure was refined using Xplor/Aria and Amber force field. We use molecular graphics (MidasPlus) to check the results of our calculations, and display the NMR constraints with the program noeshow. The interactive process of examining the structure and adding in restraints is heavily dependent on graphics since we have such a great deal of spectral overlap.

我们已经确定了一个重组片段的结构 (90-231)叙利亚仓鼠PrP基因产物的三维表达 异核核磁共振。Prion是一种传染性粒子，会导致致命的 人和动物的神经退行性疾病，如瘙痒病 绵羊，疯牛病，库鲁，克鲁兹菲尔德-雅各布， Gerstmann-Staussler-Scheinker病和致死性家族性失眠 人类。这种疾病的过程是不寻常的，因为它是通过 普恩蛋白与正常人的构象变化 细胞形态(PrPc，主要是α螺旋)到异常 汇总测试表表格(PrP Scrapie)。PRP的测定 结构对于理解Pron疾病很重要， 和药物设计。我们使用了异核核磁共振技术， 图形核磁共振软件Sparky进行共振赋值和NOE 交叉峰分配法测定PrP(90-231) 结构。使用Xplor/Aria和Amber Force改进了结构 菲尔德。我们使用分子图形(MidasPlus)来检查结果 我们的计算，并用程序显示核磁共振约束 小道消息。检查结构和结构的交互过程 添加约束在很大程度上取决于图形，因为我们有 如此多的光谱重叠。