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Protein Engineering for New Functional Hemoproteins Based on Module Substitution

基于模块替换的新型功能性血红素蛋白的蛋白质工程

基本信息

批准号：
07409003
负责人：
MORISHIMA Isao
金额：
$ 19.65万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07409003/
关键词：
Module Exon Shaffling Globin エクソンジャフリング

项目摘要

The primary results in this research project are as followa :(1)Module Substitution in Globins and Peroxidases. The structural and functional properties of the module-substituted globins and peroxidases have been characterized. Most of the module-substituted proteins exhibited highly destabilized protein structure, probably due to the missing or severe perturbation in the key interactions between the modules. The destabilized protein structure also interfered the formation of the specific dimers or tetramers in globins and enzymatic activity in peroxidases. It can be, therefore, concluded that the module-module interactions are also essential to design new stable and functional proteins as well as the module substitution.(2)Identification of New Module Structure in Globins. The amino acid substituteions based on the structural unit of wchic boundaries are located at the middle of the conventional modules have revealed that the module previously proposed can be divided into new and smaller structural units. In this research project, I focused upon one of the newly identified structural units, which includes the iron-liganded histidine and about 20 amino acid residues in the proximal site, "sub-module m6". The substitution of the sub-module m6 in globins drastically affect the electronic state of heme and configuration of the iron-liganded histidine, indicating that the sub-module m6 would be a "heme binding modules" respondible for the heme binding structure.

本课题的主要研究结果如下：（1）球蛋白和过氧化物酶的模块替换。已被表征的模块取代的球蛋白和过氧化物酶的结构和功能特性。大多数模块取代的蛋白质表现出高度不稳定的蛋白质结构，可能是由于模块之间的关键相互作用的缺失或严重扰动。不稳定的蛋白质结构也干扰了球蛋白中特异性二聚体或四聚体的形成和过氧化物酶的酶活性。因此，可以得出结论，模块间的相互作用对于设计新的稳定和功能性蛋白质以及模块替换也是必不可少的。（2）球蛋白新模块结构的鉴定。基于结构单元的氨基酸取代基位于传统模块的中间，表明以前提出的模块可以划分为新的更小的结构单元。在本研究项目中，我重点研究了一个新发现的结构单元，它包括铁配体组氨酸和近端位点的约20个氨基酸残基，“子模块m6”。m6亚模块的取代显著影响了血红素的电子态和铁配体组氨酸的构型，表明m6亚模块可能是一个负责血红素结合结构的“血红素结合模块”。