权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Protein structure, comparison, prediction, and design

蛋白质结构、比较、预测和设计

基本信息

批准号：
07280101
负责人：
GO Nobuhiro
金额：
$ 217.73万
依托单位：
KYOTO UNIVERSITY (1996-1999)Nagoya University (1995)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1999
项目状态：
已结题

项目摘要

Natural history group (Go, Yura, Wako, Nishikawa, Mitaku, and Umeyama)From a classification of the spatial arrangements of the secondary structure elements, Go discovered 'the symmetry rule', whish states that apair of similar protein folds, having no common ancestor, tend to possessan internal symmetry in their fold. Yura found two types of 'modules', a phosphate binding module observed commonly in polymerases and transcription factors, and a substrate-specificity determining module of peroxidases. A newly developed method for detecting similarity in the atomic level revealed a lot of similar ATP binding structures in totally different folds (Go). Wako developed an efficient algorithm of expressing the local environment by a code representation. A new secondary structure prediction method was developed by Nishikawa, who applied the threading method for this purpose. As for the structural prediction for membrane bound proteins, Mitaku improved his method to predict the structure of bacteriorhodopsin correctly. Umeyama established a fully automated algorithm of homology modeling, which is estimated to give a sufficient accuracy.Design group (Yomo and Ishimori)Yomo found in random mutagenesis experiments on catalase that the thermal stability and activity of the protein is extremely robust against mutations, and that a possibility of the functional optimization by the evolutional engineering technique can enormously enhanced by the elongation of the chain length. The concept of 'module' was applied to produce chimera hemoglobin, which was synthesized by exchanging its modules each other. From such chimera proteins, Ishimori confirmed that the structural unit, module, works not only as the unit of maintaining the protein stability, but also as a unit for realizing the function of hemoglobin.

自然史组（Go, Yura, Wako, Nishikawa， Mitaku和Umeyama）从二级结构元素的空间排列分类中，Go发现了“对称规则”，即一对相似的蛋白质折叠，没有共同的祖先，往往在其折叠中具有内部对称性。Yura发现了两种类型的“模块”，一种是在聚合酶和转录因子中常见的磷酸盐结合模块，另一种是过氧化物酶的底物特异性决定模块。一种在原子水平上检测相似性的新方法揭示了许多相似的ATP结合结构在完全不同的折叠中（Go）。Wako开发了一种通过代码表示来表达局部环境的有效算法。Nishikawa提出了一种新的二级结构预测方法，他将线程法应用于此。在膜结合蛋白的结构预测方面，Mitaku改进了他的方法，正确预测了细菌视紫红质的结构。Umeyama建立了一个完全自动化的同调建模算法，估计可以给出足够的精度。设计小组（Yomo and Ishimori）Yomo在对过氧化氢酶的随机诱变实验中发现，该蛋白的热稳定性和抗突变活性非常强，并且通过延长链长可以极大地增强通过进化工程技术进行功能优化的可能性。“模块”的概念被应用于生产嵌合体血红蛋白，它是通过相互交换模块来合成的。从这些嵌合体蛋白中，Ishimori证实了结构单元模块不仅是维持蛋白质稳定性的单元，也是实现血红蛋白功能的单元。