Altered Drug Transport by Plasmodium falciparum Chloroquine Resistance Transporter Isoforms Harboring Mutations Associated with Piperaquine Resistance.,Biochemistry

当前位置： X-MOL 学术 › Biochemistry › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Altered Drug Transport by Plasmodium falciparum Chloroquine Resistance Transporter Isoforms Harboring Mutations Associated with Piperaquine Resistance.
Biochemistry ( IF 2.9 ) Pub Date : 2020-06-26 , DOI: 10.1021/acs.biochem.0c00247
Bryce Riegel ₁ , Paul D Roepe ₁

Affiliation

Patterns of multiple amino acid substitutions in the Plasmodium falciparum chloroquine resistance transporter (PfCRT, UniProtKB Q8IBZ9) have previously been shown to mediate chloroquine resistance in P. falciparum malarial parasites. Recent reports suggest that novel mutations in PfCRT may mediate resistance to piperaquine (PPQ), which is used extensively as a partner drug in one prominent artemisinin combination therapy. How these novel PfCRT isoforms might mediate PPQ resistance (PPQR) is not known. Using codon optimization and other previously perfected methods for PfCRT analysis in yeast, we have expressed all known PPQR-associated PfCRT isoforms in Saccharomyces cerevisiae yeast and tested whether these isoforms catalyze PPQ transport. Relationships between relative PPQ and CQ transport are analyzed for these isoforms versus other previously recognized drug resistance-associated PfCRT isoforms.

中文翻译：

恶性疟原虫氯喹抗性转运蛋白同工型具有与哌喹抗性有关的突变，改变了药物的转运。

恶性疟原虫氯喹抗性转运蛋白（PfCRT，UniProtKB Q8IBZ9）中多个氨基酸取代的模式先前已显示出可在恶性疟原虫疟疾寄生虫中介导氯喹抗性。最近的报道表明，PfCRT的新突变可能介导了对哌喹（PPQ）的抗性，后者在一种重要的青蒿素联合疗法中被广泛用作伴侣药物。这些新颖的PfCRT亚型如何介导PPQ抗性（PPQR）尚不清楚。使用密码子优化和其他先前完善的方法进行酵母PfCRT分析，我们已在酿酒酵母中表达了所有已知的与PPQR相关的PfCRT亚型。酵母并测试这些同工型是否催化PPQ转运。针对这些同工型与其他先前公认的耐药性相关的PfCRT同工型，分析了相对PPQ和CQ转运之间的关系。

更新日期：2020-07-14

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11