Dynamical and Functional Characterization of IGPS

描述（由申请人提供）：蛋白质的灵活性已经被很好地观察到，这种动态在蛋白质功能中的作用似乎是不可避免的。我的研究兴趣是蛋白质的动态和结构特性与蛋白质功能之间的关系。该研究将在细菌异二聚体酶复合物咪唑甘油磷酸（IGP）合成酶上进行，这是一种连接氨基酸和核苷酸生物合成的关键代谢酶。生化和x射线晶体学研究表明，这两个反应在不同的活性位点之间存在紧密耦合，表明其在功能中起动力学作用。尽管如此，关于变构相互作用的确切机制的细节仍然未知，这是我研究这种酶复合物动力学的动力。核磁共振使非扰动测量残渣残渣动力学。单独比较IGP合成酶运动和底物或底物类似物-酶复合物将有助于表征对功能的结构和动力学贡献。该研究将通过结合核磁共振结构和自旋松弛测量与IGP合成酶活性的生化表征来进行。

DESCRIPTION (provided by applicant): Flexibility of proteins has been well observed and a role of such dynamics in protein functions seems inevitable. My research interest is the relationship between the dynamic and structural properties of proteins and the function of proteins. The study will be performed on the bacterial heterodimeric enzyme complex imidazole glycerol phosphate (IGP) synthase, a key metabolic enzyme which links amino acid and nucleotide biosynthesis. Biochemical and x-ray crystallographic studies indicate a tight coupling between the two reactions in distinct active sites, suggesting a dynamical role in function. Nonetheless, the details on the exact mechanism regarding the allosteric interactions are still unknown, and that is my very motivation to investigate the dynamics of this enzyme complex. NMR enables non-perturbing measurement of the residue- by-residue dynamics. Comparison of IGP synthase motion alone and substrate(s) or substrate analogue(s)-enzyme complexes will enable characterization of structural and dynamical contributions to function. The study will be carried out by combining NMR structural and spin-relaxation measurements with biochemical characterization of IGP synthase activity.