STRUCTURE DETERMINATION OF RPRP(90 231)

RPRP的结构确定(90 231)

• 批准号: 6456743
• 负责人: HE LIU
• 金额: $ 27.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6456743
• 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.

我们已经确定了重组片段的结构 （90-231）的叙利亚仓鼠PrP基因产物， 杂原子NMR。 朊病毒是一种传染性粒子， 人类和动物的神经退行性疾病，如羊瘙痒症， 绵羊，疯牛病，库鲁病，克鲁茨-雅各布病， Gerstmann-Staussler-Scheinker病和致命的家族性失眠症 人类 这种疾病的过程是不寻常的，因为它是通过 朊病毒蛋白质构象的改变 细胞形式（PrPc，主要是α螺旋）到异常 聚集的β-折叠形式（PrP Scrapie）。 Prp的测定 结构对于理解朊病毒疾病， 药物设计。 我们使用异相NMR技术， 图形NMR软件Sparky进行共振分配和NOE 用于测定PrP（90-231）的交叉峰归属 结构 使用Xplor/Aria和Amber force对结构进行了优化 领域 我们使用分子图形（MidasPlus）来检查 我们的计算，并显示与程序的NMR约束 不知道 审查结构和 添加约束严重依赖于图形，因为我们有 如此多的光谱重叠。