Pino, PacoPacoPinoCaldelari, RetoRetoCaldelariMukherjee, BudhadityaBudhadityaMukherjeeVahokoski, JuhaJuhaVahokoskiKlages, NatachaNatachaKlagesMaco, BohumilBohumilMacoCollins, Christine RChristine RCollinsBlackman, Michael JMichael JBlackmanKursula, InariInariKursulaHeussler, VolkerVolkerHeussler0000-0001-8028-9825Brochet, MathieuMathieuBrochetSoldati-Favre, DominiqueDominiqueSoldati-Favre2024-10-252024-10-252017-10-27https://boris-portal.unibe.ch/handle/20.500.12422/155699Regulated 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.en500 - Science::570 - Life sciences; biology600 - Technology::610 - Medicine & healtharticle10.7892/boris.1071982907477510.1126/science.aaf8675