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 和更复杂的系统，并提高这些 解决方案的结构可以得到，以及对研究的目的， 结构和功能的关联。 已经确定和分析了几种蛋白质的结构。 这些 包括细胞因子白细胞介素-4（钙调蛋白与白细胞介素-4的复合物）。 靶肽来自骨骼肌肌球蛋白轻链激酶， 人增强子结合蛋白MBP-1的锌指结构域和E3 二氢硫辛酰胺琥珀酰转移酶核心的结合结构域 2-（斜体）E.杆菌 这些研究开发了许多新的3D和4D异谱NMR 实验以显著提高光谱分辨率， 解决较大蛋白质中的分配模糊性。位置和效果 链球菌蛋白G的IgG结合域中的结构水 已经被调查，并提供了第一个水的示范， 溶液中螺旋线的诱导变形。最后，详细分析 已经进行了人硫氧还蛋白的静电性质， 与其结构有关。

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 allows the investigation of larger and more complex systems, and increases the precision with which these solution structures can be obtained, as well as on studies aimed at correlating structure and function. Structures for several proteins have been determined and analyzed. These include the cytokine interleukin-4, the complex of calmodulin with a target peptide from skeletal muscle myosin light chain kinase, the double zinc finger domain of the human enhancer binding protein MBP-1, and the E3 binding domain of the dihydrolipoamide succinyl transferase core from the 2-oxoglutarate dehydrogenase multienzyme complex of (italic) E. coli. 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 location and effect of structural water in the IgG binding domain of Streptococcal protein G has been investigated and has provided the first demonstration of a water induced distortion of a helix in solution. Finally, a detailed analysis of the electrostatic properties of human thioredoxin has been carried out and related to its structure.