INVESTIGATIONS OF MACROMOLECULAR STRUCTURES AND DYNAMICS IN SOLUTION BY NMR

本实验室的总体研究目标集中在 尽可能完整地描述结构， 溶液中的肽、蛋白质、核酸及其复合物， 主要通过NMR光谱法。目前特别强调的是， 发展的方法，使调查更大的 和复杂的系统，以及提高精度，这些 可以获得溶液结构，研究旨在关联 结构和功能，以及旨在研究蛋白质的实验 折页. 已经确定和分析了几种蛋白质的结构。 这些 包括氧化的和还原的人硫氧还蛋白， p53结构域、细胞因子hMIP-1-β和蛔虫胰蛋白酶 抑制剂. 这些研究开发了许多新颖的3D和4D 异频NMR实验，以显着提高光谱 分辨率，从而解决较大蛋白质中的分配模糊性。 白细胞介素-8与N-末端细胞质相互作用的位点 其细胞表面受体的一部分已被确定， 链球菌G的IgG结合域的动力学已经被 研究了 最后，对高密度聚乙烯的折叠途径和动力学进行了研究。 链球菌蛋白G的稳定的小IgG结合结构域已经被 研究了

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 and complex systems as well as increase the precision with which these solution structures can be obtained, studies aimed at correlating structure and function, and experiments aimed at investigating protein folding. Structures for several proteins have been determined and analyzed. These include oxidized and reduced human thioredoxin, the oligomerization domain of p53, the cytokine hMIP-1-beta, and the Ascaris trypsin inhibitor. These studies have exploited many novel 3D and 4D heteronuclear NMR experiments to dramatically increase spectral resolution and thereby resolve assignment ambiguities in larger proteins. The site of interaction of interleukin-8 with the N-terminal cytoplasmic portion of its cell surface receptor has been identified, and the dynamics of the IgG binding domain of Streptococcal G have been investigated. Finally, the folding pathway and kinetics of the highly stable small IgG binding domain of Streptococcal protein G has been studied.