酿酒酵母是目前研究背景最为清楚的单细胞真核生物,迄今已知有78个基因编码的蛋白质直接参与其氧化应激反应.这些蛋白质按照功能可以被分为三大类:感应蛋白、调控蛋白和效应蛋白.我们从效应蛋白出发,沿着硫氧还蛋白系统和谷氧还蛋白系统的电子传递路线,逐一解析了所有关键节点蛋白质的三维结构.结合这些蛋白质的生化性质研究、蛋白质-蛋白质复合物的鉴定和结构解析,以及酵母基因组数据库中日益更新的实验数据,我们已初步建立参与酵母氧化应激反应的效应蛋白在原子分辨率上的相互作用网络.这些研究将为我们理解人类氧化应激反应的作用机理提供重要提示,进而可能用于疾病治疗和抗衰老药物的设计.
The yeast Saccharomyces cerevisiae is a unicellular organism with the best research background. To date, there are 78 genes annotated to the term of response to oxidative stress in yeast. The encoded proteins of these genes could be classified into three groups, sensors, regulators and effectors. Taking advantage of the methodology of structural genomics, we started with all of the effectors and have solved all key effectors along the electron transfer pathway of thioredoxin and glutaredoxin systems. Moreover, a series of assays will be set up to identify the potential biochemical activities of the important effectors. Biochemical assays, in combination with protein-protein complex identification and structure solution, and the fast growing information in yeast databases, enable us to remodel a structure-based protein-protein interaction network of effectors in response to oxidative stress. These researches will provide us with some hints to design potential drugs for preventing oxidative stress-related diseases and aging.