A multistage antimalarial targets the plasmepsins IX and X essential for invasion and egress.

Pino, P; Caldelari, R; Mukherjee, B; Vahokoski, J; Klages, N; Maco, B; Collins, CR; Blackman, MJ; Kursula, I; Heussler, V; Brochet, M; Soldati-Favre, D; (2017) A multistage antimalarial targets the plasmepsins IX and X essential for invasion and egress. Technical Report. American Association for the Advancement of Science. DOI: https://doi.org/10.1126/science.aaf8675

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: 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.<br/>

Item Type: Monograph
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
PubMed ID: 29074775
Web of Science ID: 413757500045
URI: http://researchonline.lshtm.ac.uk/id/eprint/4609952

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