A multistage antimalarial targets the plasmepsins IX and X essential for invasion and egress.
In: Science, Jg. 358 (2017-10-27), Heft 6362, S. 522-528
academicJournal
Zugriff:
Regulated exocytosis by secretory organelles is important for malaria parasite invasion and egress. Many parasite effector proteins, including perforins, adhesins, and proteases, are extensively proteolytically processed both pre- and postexocytosis. Here we report the multistage antiplasmodial activity of the aspartic protease inhibitor hydroxyl-ethyl-amine–based scaffold compound 49c. This scaffold inhibits the preexocytosis processing of several secreted rhoptry and microneme proteins by targeting the corresponding maturases plasmepsins IX (PMIX) and X (PMX), respectively. Conditional excision of PMIX revealed its crucial role in invasion, and recombinantly active PMIX and PMX cleave egress and invasion factors in a 49c-sensitive manner. [ABSTRACT FROM AUTHOR]
Titel: |
A multistage antimalarial targets the plasmepsins IX and X essential for invasion and egress.
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Autor/in / Beteiligte Person: | Pino, Paco ; Caldelari, Reto ; Mukherjee, Budhaditya ; Vahokoski, Juha ; Klages, Natacha ; Maco, Bohumil ; Collins, Christine R. ; Blackman, Michael J. ; Kursula, Inari ; Heussler, Volker ; Brochet, Mathieu ; Soldati-Favre1, Dominique |
Zeitschrift: | Science, Jg. 358 (2017-10-27), Heft 6362, S. 522-528 |
Veröffentlichung: | 2017 |
Medientyp: | academicJournal |
ISSN: | 0036-8075 (print) |
DOI: | 10.1126/science.aaf8675 |
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