Glutathione dependent metabolism of the malarial parasite Plasmodium falciparum

疟疾寄生虫恶性疟原虫的谷胱甘肽依赖性代谢

• 批准号: 155465690
• 负责人: Professorin Dr. Katja Becker
• 金额: --
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2011-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/155465690?language=en
• 关键词: Glutathione; dependent; metabolism; malarial; parasite

For survival and growth of the malarial parasite Plasmodium falciparum (Pf) glutathione homeostasis is of particular importance. The tripeptide glutathione (γ-Glu-Cys-Gly) serves for detoxifying electrophiles such as hemin and methylglyoxal and for quenching reactive oxygen and nitrogen species produced by the high metabolic rate of the parasite, the immune systems of the hosts, and as a byproduct of hemoglobin digestion. Apart from antioxidant defense and redox regulation, the glutathione system has been linked to the detoxification of antimalarial drugs and resistance mechanisms. Within the frame of the proposed project, we plan to continue our work on the glutathione-dependent redox milieu and glutathione-dependent proteins of the malarial parasite. We aim at focusing on the following four aspects: (1) establishing redox sensitive GFP (the glutaredoxin1-roGFP2 fusion protein) as tool for dynamic live imaging of the glutathione redox potential in Plasmodium, (2) determining the subcellular localization of glutathione-related proteins, (3) characterizing glutathionylation patterns in the proteome of malarial parasites under various conditions, and (4) studying the structural, biochemical and kinetic effects of glutathionylation on selected target proteins.

对于恶性疟原虫（Pf）的生存和生长，谷胱甘肽的稳态是特别重要的。三肽谷胱甘肽（γ-Glu-Cys-Gly）用于解毒亲电体（如氯化血红素和甲基乙二醛），并用于淬灭由寄生虫、宿主免疫系统的高代谢率产生的活性氧和氮物质，以及作为血红蛋白消化的副产物。除了抗氧化防御和氧化还原调节外，谷胱甘肽系统还与抗疟药物的解毒和耐药机制有关。在拟议项目的框架内，我们计划继续我们的工作谷胱甘肽依赖的氧化还原环境和谷胱甘肽依赖的蛋白质的疟疾寄生虫。我们的目标是重点关注以下四个方面：（1）建立氧化还原敏感的GFP，（谷氧还蛋白1-roGFP 2融合蛋白）作为疟原虫中谷胱甘肽氧化还原电位的动态活体成像工具，（2）确定谷胱甘肽相关蛋白的亚细胞定位，（3）表征各种条件下疟疾寄生虫蛋白质组中的谷胱甘肽化模式，和（4）研究结构，谷胱甘肽化对所选靶蛋白的生物化学和动力学影响。