Structure and Dynamics of Proteins from NMR Orientational Data

根据 NMR 定向数据研究蛋白质的结构和动力学

• 批准号: 9726341
• 负责人: James Prestegard
• 金额: $ 33万
• 依托单位: University of Georgia Research Foundation Inc
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9726341&HistoricalAwards=false
• 关键词: Structure; Dynamics; Proteins; NMR; Orientational

9726341 Prestegard The overall objective of this work is to explore a potential new source of information on protein structure and dynamics in solution. The new information comes from residual dipolar couplings recently seen in NMR spectra of molecules with highly anisotropic magnetic susceptibilities when these molecules are placed in very high magnetic fields. The contributions are dependent on the orientation of the vector connecting the nuclei relative to the axes of a molecular susceptibility tensor. Measurement, thus, can provide structural information by constraining orientations of remote parts of large molecules in ways that are inaccessible using existing NOE based distance constraints. The couplings are also subject to the effects of motional averaging. This is particularly important because the range of motions contributing to the averaging process is much larger than those contributing to commonly measured NMR relaxation parameters. Experiments may, therefore, give insight into large amplitude, slower, motions that are among those most likely to contribute to protein function. Devising and testing methods for measurement and analysis of residual dipolar couplings is the primary object of this research. Two paramagnetic proteins, myoglobin and cytochrome b5, are chosen as targets for preliminary application. Both are well characterized structurally and should serve as suitable benchmarks for a new structural strategy. However, both have also been the subject of much debate as to motional contributions to function. Methods developed and applied to these proteins should contribute to resolution of this debate. ***

9726341 Prestegard这项工作的总体目标是探索一个潜在的新的信息来源的蛋白质结构和动力学的解决方案。 新的信息来自残余偶极耦合最近看到的NMR谱的分子具有高度各向异性的磁磁化率时，这些分子被放置在非常高的磁场。 的贡献是依赖于相对于分子磁化率张量的轴连接的核的矢量的方向。 因此，测量可以通过以使用现有的基于NOE的距离约束无法访问的方式约束大分子的远程部分的取向来提供结构信息。 耦合也受到运动平均的影响。 这是特别重要的，因为对平均过程有贡献的运动范围比对通常测量的NMR弛豫参数有贡献的运动范围大得多。 因此，实验可能会让我们深入了解大振幅、较慢的运动，这些运动最有可能有助于蛋白质的功能。 本研究的主要目的是设计和测试残余偶极耦合的测量和分析方法。 两个顺磁性蛋白，肌红蛋白和细胞色素b5被选为初步应用的目标。 两者在结构上都有很好的特点，应作为新结构战略的适当基准。 然而，这两个也一直是许多辩论的主题，以运动的贡献功能。开发和应用于这些蛋白质的方法应有助于解决这一争论。 ***