دورية أكاديمية
Genetic and chemical validation of Plasmodium falciparum aminopeptidase PfA-M17 as a drug target in the hemoglobin digestion pathway
| العنوان: | Genetic and chemical validation of Plasmodium falciparum aminopeptidase PfA-M17 as a drug target in the hemoglobin digestion pathway |
|---|---|
| المؤلفون: | Rebecca CS Edgar, Ghizal Siddiqui, Katheryn Hjerrild, Tess R Malcolm, Natalie B Vinh, Chaille T Webb, Clare Holmes, Christopher A MacRaild, Hope C Chernih, Willy W Suen, Natalie A Counihan, Darren J Creek, Peter J Scammells, Sheena McGowan, Tania F de Koning-Ward |
| المصدر: | eLife, Vol 11 (2022) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | P. falciparum, hemoglobin digestion, aminopeptidase, drug target, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | Plasmodium falciparum, the causative agent of malaria, remains a global health threat as parasites continue to develop resistance to antimalarial drugs used throughout the world. Accordingly, drugs with novel modes of action are desperately required to combat malaria. P. falciparum parasites infect human red blood cells where they digest the host’s main protein constituent, hemoglobin. Leucine aminopeptidase PfA-M17 is one of several aminopeptidases that have been implicated in the last step of this digestive pathway. Here, we use both reverse genetics and a compound specifically designed to inhibit the activity of PfA-M17 to show that PfA-M17 is essential for P. falciparum survival as it provides parasites with free amino acids for growth, many of which are highly likely to originate from hemoglobin. We further show that loss of PfA-M17 results in parasites exhibiting multiple digestive vacuoles at the trophozoite stage. In contrast to other hemoglobin-degrading proteases that have overlapping redundant functions, we validate PfA-M17 as a potential novel drug target. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| Relation: | https://elifesciences.org/articles/80813; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.80813 |
| URL الوصول: | https://doaj.org/article/0679868db9304f46bdc0d01432a2d431 |
| رقم الأكسشن: | edsdoj.0679868db9304f46bdc0d01432a2d431 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
|---|---|
| DOI: | 10.7554/eLife.80813 |