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Analysis of cooperative hydration effect on functions of biomacromolecules

协同水合对生物大分子功能的影响分析

基本信息

批准号：
15560672
负责人：
MIYAWAKI Osato
金额：
$ 2.24万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

As for biomacromolecules such as proteins and polysaccharides, their functions are strongly related to their hydration state. In spite of the importance of the hydration of macromolecules, functions of biomacromolecules have been extensively analyzed mostly from the standpoint of macromolecular side and there seem to be insufficient research attempts to analyze functions of biomacromolecules from the viewpoint of solvent side, especially from water Generally, lots of water molecules are involved in the hydration of biomacromolecules so that these water molecules are expected to react cooperatively on the functions of macromolecules.In the present research, the relationship between the cooperative hydration effect of biomacromolecules, and thermal stability of proteins, subunit interactions, enzyme functions, and sol-gel transitions have been analyzed by using the solution thermodynamic approach. As a result, considerable changes in the hydration states were estimated to occur in the protein unfolding, subunit dissociation, and sol-gel transition so that it was very important to take the water activity into account to analyze these phenomena. In consideration of this, a new thermodynamic model was proposed for the first time to analyze functions of biomacromolecules reflecting the effect of hydration state, which was influenced by the water activity. By using this model, thermal stability of lysozyme and alcohol dehydrogenase, and sol-gel transition of gelatin were successfully analyzed and melting temperature of proteins and sol-gel transition temperature of gelatin were proved to be linear dependent on the water activity of the system. In addition, not only the effect of water activity but also the effect of the solvent structure observed on various functions of biomacromolecules, which could be correlated to the water structure parameters reported in the literature.

对于生物大分子，如蛋白质和多糖，它们的功能与其水合状态密切相关。尽管大分子的水合作用很重要，但人们对生物大分子的功能分析大多是从大分子的角度进行的，而从溶剂的角度，特别是从水的角度来分析生物大分子的功能的研究似乎还不够。生物大分子的水合作用涉及大量的水分子，因此这些水分子可以协同作用于大分子的功能。本研究采用溶液热力学方法，分析了生物大分子的协同水化效应与蛋白质热稳定性、亚基相互作用、酶功能和溶胶-凝胶转变之间的关系。因此，估计在蛋白质展开、亚基解离和溶胶-凝胶转变过程中水合状态发生了相当大的变化，因此考虑水活度来分析这些现象是非常重要的。鉴于此，本文首次提出了一个新的热力学模型来分析生物大分子反映水化状态影响的功能，而水化状态受水活度的影响。利用该模型成功地分析了溶菌酶和醇脱氢酶的热稳定性以及明胶的溶胶-凝胶转变，并证明了蛋白质的熔化温度和明胶的溶胶-凝胶转变温度与体系的水活度呈线性关系。此外，除了水活度的影响外，还观察到溶剂结构对生物大分子各种功能的影响，这可能与文献中报道的水结构参数有关。