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.

为了建立集成分子系统的设计和构建原理，我们研究了生物分子系统的结构和工作设计。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，两者都是具有集成功能元件的多功能巨蛋白。就脂肪酸合成酶而言，不同部分反应的七种酶被整合成具有明确目的的单一功能单元。当整合成两个活性中心的七种酶在20nmxl5nmx7nm的有限空间内工作时，我们发现两个活性中心存在协同的触发器式运动。正如活性-粘度关系的实验结果清楚表明的那样，这种运动可能与溶剂粘度和波动在流体动力学上耦合。大规模整合蛋白质的结构域和亚基的粘度依赖性运动将很容易与整个反应的化学速率决定步骤结合起来。发现蛋白质的运动部分和添加到蛋白质水溶液中的粘性原分子之间的流体动力耦合强烈依赖于粘性原的尺寸。未来将利用这一发现来估计蛋白质部分移动元件的大小。 α-2-巨球蛋白的大规模亚基重排也表明了蛋白质运动与溶剂的类似流体动力学耦合。在这项研究中，我们明确了集成系统元件与溶剂之间的流体动力耦合是在分子水平上集成系统设计中需要考虑的一个非常重要的因素。