日本血吸虫抗氧化靶标蛋白SjPrx1及SjTGR抑制剂筛选的结构基础

项目名称： 日本血吸虫抗氧化靶标蛋白SjPrx1及SjTGR抑制剂筛选的结构基础

项目编号： No.31260206

项目类型： 地区科学基金项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 李永东

作者单位： 赣南师范学院

项目金额： 50万元

中文摘要： 日本血吸虫病是严重危害我国人民生命健康的传染性疾病，吡喹酮（Praziquantel）是有效的化疗药物。该药物的大量重复使用有可能促使抗药虫株的出现，产生严重的公共卫生危机，事实上曼氏血吸虫抗药虫株已有报道。本研究选取新近发现的血吸虫抗氧化药物靶标蛋白-日本血吸虫硫氧还蛋白过氧化物酶（SjPrx1）及硫氧还蛋白谷胱甘肽还原酶（SjTGR）为对象，构建重组蛋白表达系统制备具有全部生物活性的SjTGR和SjPrx1蛋白酶，研究其生物活性；解析靶标蛋白单体及与其抑制剂作用的复合物高分辨率精细结构；建立以靶标蛋白为目标的化学抑制剂筛选系统，阐明其与化学抑制剂的作用机制。该研究将为发现设计出具有高亲和性与强特异性的抗血吸虫病化学治疗新型药物打下坚实基础。

中文关键词： 日本血吸虫；硫氧还蛋白谷胱甘肽还原酶；硫氧还蛋白过氧化物酶；抑制剂；药物靶标

英文摘要： Schistosoma japonicum, a causative agent of schistosomiasis, is a parasitic disease affecting millions of people in China. Current treatment relies on a single drug of praziquantel, however, therapy based on just a single compound is at risky because of the high probability to cause resistance. Indeed, schistosome strains displaying low praziquantel susceptibility have already been reported. This study focus on the antioxidant proteins of SjPrx1 (Peroxiredoxins from Schistosoma Japonicum) and SjTGR (Thioredoxin Glutathione Reductase from Schistosoma Japonicum）which have been suggested as the drug targets for antischistosomal therapy. The recombinant expression system will be constructed for prepareation of proteins and the biological activities of enzymes will be determined. Also we will solve the crystal structures of proteins and the complex with its inhibitors. The screen system for drug design and development based on the three dimension structures will be set up. These results will be probably lay a solid foundation for development of chemical drugs with high affinity and specificity targeting on these proteins.

英文关键词： Schistosoma Japonicum；Thioredoxin Glutathione Reductase；Peroxiredoxins；Inhibitor；Antioxidant