Nasamu, A, Glushakova, S, Russo, I, Vaupel, B, Oksman, A, Kim, A, Fremont, D, Tolia, N, Beck, J, Meyers, M, Niles, J, Zimmerberg, J and Goldberg, D (2017) Plasmepsins IX and X are essential and druggable mediators of malaria parasite egress and invasion. Science, 358 (6362). 518 - 522. ISSN 0036-8075

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Proteases of the malaria parasite Plasmodium falciparum have long been investigated as drug targets. The P. falciparum genome encodes 10 aspartic proteases called plasmepsins, which are involved in diverse cellular processes. Most have been studied extensively but the functions of plasmepsins IX and X (PMIX and PMX) were unknown. Here we show that PMIX is essential for erythrocyte invasion, acting on rhoptry secretory organelle biogenesis. In contrast, PMX is essential for both egress and invasion, controlling maturation of the subtilisin-like serine protease SUB1 in exoneme secretory vesicles. We have identified compounds with potent antimalarial activity targeting PMX, including a compound known to have oral efficacy in a mouse model of malaria.

Item Type: Article
Additional Information: Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Subjects: Q Science > QH Natural history
Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Natural Sciences > School of Life Sciences
Depositing User: Symplectic
Date Deposited: 09 Apr 2019 11:01
Last Modified: 15 Apr 2019 15:19

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