潜在的蛋氨酸合酶的抗疟靶标易损性。
Antimalarial target vulnerability of the putative methionine synthase.
机构信息
Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Bangkok, Thailand.
National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathum Thani, Thailand.
出版信息
PeerJ. 2024 Jan 15;12:e16595. doi: 10.7717/peerj.16595. eCollection 2024.
BACKGROUND
possesses a cobalamin-dependent methionine synthase (MS). MS is putatively encoded by the PF3D7_1233700 gene, which is orthologous and syntenic in . However, its vulnerability as an antimalarial target has not been assessed.
METHODS
We edited the PF3D7_1233700 and PF3D7_0417200 (dihydrofolate reductase-thymidylate synthase, DHFR-TS) genes and obtained transgenic parasites expressing epitope-tagged target proteins under the control of the ribozyme. Conditional loss-of-function mutants were obtained by treating transgenic parasites with glucosamine.
RESULTS
DHFR-TS, but not MS mutants showed a significant proliferation defect over 96 h, suggesting that MS is not a vulnerable antimalarial target.
背景
拥有钴胺素依赖性蛋氨酸合酶（MS）。MS 被推测由 PF3D7_1233700 基因编码，该基因在 中是同源和同基因的。然而，它作为抗疟靶点的脆弱性尚未得到评估。
方法
我们编辑了 PF3D7_1233700 和 PF3D7_0417200（二氢叶酸还原酶-胸苷酸合酶，DHFR-TS）基因，并获得了在核酶控制下表达表位标记靶蛋白的转基因 寄生虫。通过用葡糖胺处理转基因寄生虫获得条件功能丧失突变体。
结果
DHFR-TS 突变体而非 MS 突变体在 96 小时内表现出明显的增殖缺陷，表明 MS 不是一个脆弱的抗疟靶点。
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