DETERMINATION OF 3 DIMENSIONAL STRUCTURES OF MACROMOLECULES IN SOLUTION BY NMR

该实验室的工作重点是 测定大蛋白质的三维结构 通过NMR，特别强调蛋白质-蛋白质， 蛋白质-配体和蛋白质-DNA复合物。了相当大的努力 已被放置在三维和四维的发展， 杂原子核磁共振，以扩展核磁共振作为一种方法的应用 用于确定溶液中蛋白质的三维结构 超越了常规二维NMR（~ 100 残基）至150至400个残基范围内的分子，以及 发展新的核磁共振方法来确定长程有序 先验，包括异源数据对 扩散各向异性和残余偶极耦合的使用。 一些蛋白质的溶液结构已被确定。 这些包括转录因子GAGA的复合物， AreA和HMG-I/Y与DNA，DNA MuA结合结构域 Mu转座酶，30 kDa（259个残基）的N末端结构域， PTS途径的酶I， 具有含组氨酸蛋白的酶I的N-末端结构域 HPr（40 kDa），gp 41的完整的44 kDa三聚体胞外域， HIV-1整合酶的N-末端结构域，以及 势垒-自积分因子BAF。

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 a priori, including the dependence of heteronuclear relexation data on diffusion anisotropy and the use of residual dipolar couplings. Solution structures of a number of proteins have been determined. These include the complexes of the transcription factors GAGA, AreA and HMG-I/Y with DNA, the DNA MuA binding domains of the Mu transposase, the 30 kDa (259 residue) N terminal domain of Enzyme I of the PTS pathway, the 40 kDa complex of the N-terminal domain of enzyme I with the histidine containing protein HPr (40 kDa), the complete 44 kDa trimeric ectodomain of gp41, the N-terminal domain of HIV-1 integrase, and the barrier-to-autointegration factor BAF.