INVESTIGATIONS OF MACROMOLECULAR STRUCTURES IN SOLUTION BY NMR

本实验室整体研究的目标是围绕 实现对结构的尽可能完整的描述 溶液中的多肽、蛋白质、核酸及其络合物， 主要是通过核磁共振光谱分析。目前特别强调的是 致力于开发方法，允许对更大规模的 系统以及提高这些解决方案的精度 可以得到结构。 对几种蛋白质的结构进行了测定和分析。这些 包括人增强子结合蛋白的锌指结构域，人 硫氧还蛋白和细胞因子白介素8。这些解决方案结构 表示高分辨率结构，RMSD值约为0.4 主干为埃，所有原子为0.6-0.9埃。 除了结构研究外，新的核磁共振技术还允许详细的 研究了蛋白质动力学，并进行了详细的研究 白介素10的蛋白质。利用二维逆检测 N-15/H-L核磁共振谱、N-15自旋晶格和自旋自旋 收集并分析了松弛时间和NOE数据，演示了 主链酰胺基团在三个不同时间尺度上的运动。 对其他几种蛋白质的研究也在进行中，例如DNA结合 噬菌体Mu中的NER蛋白，几种白介素类，核糖核酸酶-H结构域 HIV-1逆转录酶与蛔虫胰酶

The objective of the overall research in this laboratory is centered on achieving as complete a description as possible for the structures of peptides, proteins, nucleic acids and their complexes in solution, principally by NMR spectroscopy. At present particular emphasis is being placed on developing approaches which allow the investigation of larger systems as well as increase the precision with which these solution structures can be obtained. Structures for several proteins have been determined and analyzed. These include the Zinc-finger domain of a human enhancer binding protein, human thioredoxin, and the cytokine interleukin-8. These solution structures represent high resolution structures, with rmsd values of approximately 0.4 angstroms for the backbone and 0.6-0.9 angstroms for all atoms. In addition to structural studies, novel NMR technology allows the detailed study of protein dynamics and a detailed investigation has been carried out for the protein interleukin-lo. Using two-dimensional inverse detected hetronuclear N-15/H-l NMR spectroscopy, N-15 spin-lattice and spin-spin relaxation times and NOE data were collected and analyzed, demonstrating motions on three different time scales for the backbone amide groups. Work is in progress on several other proteins, such as the DNA binding protein ner from phage Mu, several interleukins , the RNase-H domain of HIV-1 reverse transcriptase and Ascaris trypsin