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Deducing dynamic protein 3D structural information from X-ray crystallography and NMR

从 X 射线晶体学和 NMR 推断动态蛋白质 3D 结构信息

基本信息

批准号：
04453166
负责人：
GO Nobuhiro
金额：
$ 4.54万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

项目摘要

Dynamic 3D structural information of proteins is essential for elucidation of molecular mechanism of protein function. The purpose of this reseach project is firstly to develop new methods of analyzes of experimental X-ray crystallographic and NMR data and secondly to apply the developed methods for real systems to deduce such dynamic information. At first, we applied the new method of protein X-ray crystallographic refinement based on the normal mode concept to human lysozyme and its site-specific mutant, and demonstrated that information about anisotropic temperature factors of protein atoms and their concerted motions could be deduced. Furthermore interesting information was obtained about correlation of changes of 3D structure and fluctuation and also about molecular mechanism of enzymatic function by analyzing changes of 3D structure and fluctuation accompanied with site-derected mutation. At second, we developed a new method to deduce new information about collective motions in protein by analyzing X-ray diffuse scattering. At third, we derived a formula of expressing up to second order changes of protein atomic Cartesian coordinates for small changes of dihedral angles, and applied this formula for developing method of obtaining Lipari-Szabo order parameters from the normal mode analysis. This method will enable us to develop a new method by which dynamic as well as static protein 3D structural information can be deduced from experimental NMR data.

蛋白质的动态三维结构信息对于阐明蛋白质功能的分子机制至关重要。本研究项目的目的是首先发展新的方法来分析实验X射线晶体学和NMR数据，其次将所发展的方法应用于真实的系统来推导这种动态信息。首先，我们将基于简正模概念的蛋白质X射线晶体学精修新方法应用于人溶菌酶及其定点突变体，证明了该方法可以推导出蛋白质原子的各向异性温度因子及其协同运动的信息。通过对定点突变引起的酶的三维结构变化和波动的分析，进一步揭示了三维结构变化和波动之间的相关性以及酶功能的分子机制。其次，我们发展了一种新的方法，通过分析X射线漫散射来推断蛋白质中集体运动的新信息。第三，我们推导出了二面角微小变化时蛋白质原子笛卡尔坐标二阶变化的表达式，并应用该表达式发展了从简正模分析中获得Lipari-Szabo序参数的方法。这种方法将使我们能够开发一种新的方法，通过该方法可以从实验NMR数据中推断出动态和静态蛋白质3D结构信息。