疟疾寄生虫和人类宿主之间的二叶酸减少酶的分离调节
Kai Zhang1, Pradipsinh K Rathod
1Department of Biology, The Catholic University of America, Washington, DC 20064, USA.
概括
抗叶剂疟疾药物向的是Plasmodium falciparum二酸二酸减少酶-基酸合成酶 (DHFR-TS). 寄生虫不能补充药物失活的DHFR-TS,因为它的mRNA结合调节与人类不同.
科学领域:
- 生物化学 生物化学
- 寄生虫学的寄生虫学
- 药物发现 药物发现 药物发现
背景情况:
- 几十年来,抗叶酸药物一直用于治疗Plasmodium falciparum疟疾.
- 治疗成功往往归因于药物与目标酶,二叶酸减少酶-甲基基聚合酶 (DHFR-TS) 的结合的差异.
- 然而,DHFR-TS的调节机制也可能导致药物选择性.
研究的目的:
- 调查Plasmodium DHFR-TS的转化调节在抗叶酸药物疗效中的作用.
- 为了比较Plasmodium和人类中DHFR-TS的调节机制.
主要方法:
- 分析Plasmodium DHFR-TS的mRNA结合的情况.
- 在Plasmodium和人类系统中DHFR-TS转化调节的比较.
主要成果:
- 菌DHFR-TS结合了自己的mRNA,抑制了翻译.
- 这种mRNA结合独立于酶的活性位点.
- 抗叶酸治疗不会释放寄生虫中的这种转化抑制.
结论:
- 在DHFR-TS mRNA结合调节中的差异,而不仅仅是药物结合,有助于抗叶酸抗 Plasmodium 的选择性.
- 由于这种调节机制,寄生虫无法弥补药物诱导的酶失活.
- 这突出了抗疟疾药物开发的新目标.
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