DETERMINATION OF 3 DIMENSIONAL STRUCTURES OF MACROMOLECULES IN SOLUTION BY NMR

核磁共振法测定溶液中大分子的三维结构

• 批准号: 6161936
• 负责人: G. MARIUS CLORE
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6161936
• 关键词: DNA; DNA binding protein; Streptococcus; bacterial proteins; human immunodeficiency virus; integrase; ligands; method development; nuclear magnetic resonance spectroscopy; protein structure; solutions; structural biology; thioredoxin; transcription factor; transposon /insertion element; virus protein

Work in this laboratory has been focused on the determination of three-dimensional structures of larger proteins in solution by NMR, with a particular emphasis on protein-protein, protein-ligand and protein-DNA complexes. A considerable effort has been placed on the development of three- and four-dimensional heteronuclear NMR to extend the application of NMR as a method for determining three-dimensional structures of proteins in solution beyond the limits of conventional two-dimensional NMR (-100 residues) to molecules in the 150- to 400- residue range, and to develop new NMR methods for determining long range order of priority, including the dependence of heteronuclear relevation data on diffusion anisotropy and the use of residual dipl couplings arising from magnetic susceptibility anisotropy. Solution structures of a number of proteins have been determined. These include the complexes of the transcription factors GAGA, Are A and HMG-I/Y with DNA, the DNA MuA binding domains of the transposase, the 30 kDa (259 residue) N terminal domain of Enzyme I of the PTS pathway, the 44 kDa ectodomain of gp41, and the N-terminal domain of HIV-1 integrase.

这个实验室的工作一直集中在测定 核磁共振研究大分子蛋白质在溶液中的三维结构 特别强调蛋白质-蛋白质、蛋白质-配体和蛋白质-DNA 复合体。已经做出了相当大的努力来发展…… 扩展应用的三维和四维异核核磁共振 作为确定化合物三维结构的一种方法 超越常规二维极限的溶液中的蛋白质 核磁共振(-100个残基)到150-到400个残基范围内的分子，以及 为了开发用于确定长程优先顺序的新的核磁共振方法， 包括异核关联数据对扩散的依赖性 各向异性和磁致残余DIPL耦合的使用 磁化率各向异性。几种蛋白质的溶液结构 已经确定了。这些包括转录的复合体 GagA因子是A和HMG-I/Y与DNA结合，DNA MUA结合区 转座酶的30 kDa(259个残基)N末端结构域 PTS途径的I、gp41的44 kDa胞外区和N-末端 HIV-1整合酶结构域。