@article{3deb458ab0754a6c8f3a3fcd7232544a,
title = "Plasmepsins IX and X are essential and druggable mediators of malaria parasite egress and invasion",
abstract = "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.",
author = "Nasamu, {Armiyaw S.} and Svetlana Glushakova and Ilaria Russo and Barbara Vaupel and Anna Oksman and Kim, {Arthur S.} and Fremont, {Daved H.} and Niraj Tolia and Beck, {Josh R.} and Meyers, {Marvin J.} and Niles, {Jacquin C.} and Joshua Zimmerberg and Goldberg, {Daniel E.}",
note = "Funding Information: M. Blackman for SERA5 and SUB1 antibodies, E. Istvan for helpful suggestions, and D. Sibley for critical review of the manuscript. This work was supported by NIH grant AI-112508. J.R.B. was supported by NIH K99 grant HL133453. J.C.N. was supported by NIH P50 grant GM098792 and a grant from the Bill and Melinda Gates Foundation (OPP1069759). This work was supported in part by the Division of Intramural Research of the NICHD. This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. This license does not apply to figures/photos/artwork or other content included in the article that is credited to a third party; obtain authorization from the rights holder before using such material.",
year = "2017",
month = oct,
day = "27",
doi = "10.1126/science.aan1478",
language = "English",
volume = "358",
pages = "518--522",
journal = "Science",
issn = "0036-8075",
number = "6362",
}