Photoaffinity Labeling and Active Site Chemistry of 2-5A Synthetase and RNase L

2-5A 合成酶和 RNase L 的光亲和标记和活性位点化学

• 批准号: 8904378
• 负责人: Robert Suhadolnik
• 金额: $ 6万
• 依托单位: Temple University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-01 至 1991-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8904378&HistoricalAwards=false
• 关键词: Photoaffinity; Labeling; Active; Site; Chemistry

The long term goal of this project is to understand the nucleotide-protein interactions that are essential for activity of 2 enzymes: the dsRNA-dependent 2-5A synthetase and the 2-5A- dependent RNase L. These enzymes play an intriguing role in the antiviral and antiproliferative defense mechanisms of mammalian cells. Phosphorothioate-substituted ATP and 2-5A molecules have provided beochemical probes of these two key enzymes and have permitted the separation of the binding and activation processes required for enzyme catalysis. Photoaffinity labeling technology is being used to examine the nucleotide-protein interactions occurring during binding and activation of 2-5A synthetase and RNase L. This project investigates 2 enzymes which regulate levels of oligonucleotides in cells and play a role in the cell's defense mechanisms. In addition to the role of the 2-5A synthetase/RNase L system in defense against virus infection, it has been suggested that the system may also be involved in the control of cell growth, proliferation and differentiation. Fundamental questions remain and are being addressed.

该项目的长期目标是了解 对于活性至关重要的核苷酸-蛋白质相互作用 2种酶：dsRNA依赖性2-5A合成酶和2-5A- 依赖性核糖核酸酶 这些酶在生物体内起着有趣的作用， 哺乳动物的抗病毒和抗增殖防御机制 细胞 硫代磷酸酯取代的ATP和2-5A分子具有 提供了这两种关键酶的生物化学探针， 允许结合和激活过程的分离 酶催化所必需的。 光亲和标记技术 被用来研究核苷酸-蛋白质相互作用 在2-5A合成酶的结合和活化过程中发生， 核糖核酸酶属 该项目研究了两种调节蛋白质水平的酶， 寡核苷酸在细胞中发挥作用， 机制等 除了2-5A合成酶/核糖核酸酶的作用外， L系统在防御病毒感染方面的作用， 建议该系统也可以参与控制 细胞生长、增殖和分化。 基本 问题仍然存在，正在解决。