Oligomeric protein interference validates druggability of aspartate interconversion in Plasmodium falciparum
| العنوان: | Oligomeric protein interference validates druggability of aspartate interconversion in Plasmodium falciparum |
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| المؤلفون: | Atilio Reyes Romero, Carsten Wrenger, Sergey Lunev, Chao Wang, Marleen Linzke, Soraya S Bosch, Sabine Butzloff, Kamila Anna Meissner, Alexander Dömling, Fernando de Assis Batista, Matthew Groves, Ingrid B. Müller |
| المساهمون: | Drug Design, Medicinal Chemistry and Bioanalysis (MCB) |
| المصدر: | MicrobiologyOpen MicrobiologyOpen, 8(7):e779. Wiley MicrobiologyOpen, Vol 8, Iss 7, Pp n/a-n/a (2019) Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| بيانات النشر: | Wiley, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | AMINOTRANSFERASE, Plasmodium falciparum, Mutant, lcsh:QR1-502, Druggability, PURINE, Computational biology, Biology, METABOLISM, Microbiology, lcsh:Microbiology, MECHANISMS, 03 medical and health sciences, 0302 clinical medicine, In vivo, structural biology, Gene, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, oligomeric state, Original Articles, ANTIMALÁRICOS, biology.organism_classification, GENE, 3. Good health, Enzyme, chemistry, Structural biology, phenotypic mapping, Original Article, drug target validation, 030217 neurology & neurosurgery, Function (biology), INTERFACES |
| الوصف: | The appearance of multi‐drug resistant strains of malaria poses a major challenge to human health and validated drug targets are urgently required. To define a protein's function in vivo and thereby validate it as a drug target, highly specific tools are required that modify protein function with minimal cross‐reactivity. While modern genetic approaches often offer the desired level of target specificity, applying these techniques is frequently challenging—particularly in the most dangerous malaria parasite, Plasmodium falciparum. Our hypothesis is that such challenges can be addressed by incorporating mutant proteins within oligomeric protein complexes of the target organism in vivo. In this manuscript, we provide data to support our hypothesis by demonstrating that recombinant expression of mutant proteins within P. falciparum leverages the native protein oligomeric state to influence protein function in vivo, thereby providing a rapid validation of potential drug targets. Our data show that interference with aspartate metabolism in vivo leads to a significant hindrance in parasite survival and strongly suggest that enzymes integral to aspartate metabolism are promising targets for the discovery of novel antimalarials. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2045-8827 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4ffbccf06d28255ac3b7e7ff4edebcfc https://doi.org/10.1002/mbo3.779 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....4ffbccf06d28255ac3b7e7ff4edebcfc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20458827 |
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