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DESIGN OF MOLECULAR INTEGRATED ELEMENTS BASED ON THE FLEXIBLE HIGHER ORDER STRUCTURE

基于柔性高阶结构的分子集成元件设计

基本信息

批准号：
63580211
负责人：
IKAI Atsushi
金额：
$ 1.86万
依托单位：
TOKYO INSTITUTE OF TECHNOLOGY (1989)The University of Tokyo (1988)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

项目摘要

With the aim to establish the designing and constructing principles of integrated molecular system, we studied the structure and working design of biological molecular systems. The model system of our work was animal fatty acid synthetase and alpha-2-macroglobuin, both are multi-functional giant proteins with integrated functional elements. In the case of fatty acid synthetase, seven-enzymes of different partial reactions are integrated into a single functional unit with a definite purpose. When the seven enzymes integrated into two active centers work in a limited space of 20nmxl5nmx7nm, we found that there is a concerted flip-flop type movement of two active centers. Such a movement is probably hydrodynamically coupled with the solvent viscosity and fluctuation as the experimental results on the activity-viscosity relationship clearly indicated. The viscosity dependent movement of the domains and subunits of integrated proteins in large scale will easily be coupled with the chemical rate determining step of the entire reaction. The hydrodynamic coupling between the moving parts of proteins and viscogen molecules added to the aqueous solution of protein was found to be acutely dependent on the size of viscogen. This finding will be exploited in future to estimate the size of the moving elements on the part of the proteins. Similar hydrodynamic coupling of protein movement with solvent is also indicated in the large scale subunit rearrangement of alpha-2- macroglobulin. In this study we made it clear that the hydrodynamic coupling between the elements of integrated system with the solvent is a very important factor to be considered in the design of integrated system on the molecular level.

以建立集成分子系统的设计与构建原则为目的，对生物分子系统的结构与工作设计进行了研究。我们工作的模型系统是动物脂肪酸合成酶和α -2巨球蛋白，它们都是具有综合功能元件的多功能巨蛋白。在脂肪酸合成酶中，7种不同部分反应的酶被整合成一个单一的功能单元，具有明确的目的。当整合到两个活性中心的7种酶在20nmx15nmx7nm的有限空间内工作时，我们发现两个活性中心存在协调一致的触发器式运动。活度-粘度关系的实验结果清楚地表明，这种运动可能与溶剂粘度和波动的流体动力学耦合。大规模整合蛋白结构域和亚基的黏度依赖运动很容易与整个反应的化学速率决定步骤耦合。研究发现，加入蛋白质水溶液中的粘胶原分子与蛋白质运动部分之间的水动力耦合严重依赖于粘胶原的大小。这一发现将在未来用于估计蛋白质部分运动元素的大小。在α -2-巨球蛋白的大规模亚基重排中也显示了类似的蛋白质运动与溶剂的流体动力学耦合。本研究明确了在分子水平上设计集成体系时，集成体系各元素与溶剂之间的流体动力学耦合是一个需要考虑的重要因素。