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The secretory proteins participate in motility, invasion, and egress and are subjected to proteolytic maturation prior to organellar storage and discharge. Here we establish that Toxoplasma gondii aspartyl protease 3 (ASP3) resides in the endosomal-like compartment and is crucially associated to rhoptry discharge during invasion and to host cell plasma membrane lysis during egress. A comparison of the N-terminome, by terminal amine isotopic labelling of substrates between wild type and ASP3 depleted parasites identified microneme and rhoptry proteins as repertoire of ASP3 substrates. The role of ASP3 as a maturase for previously described and newly identified secretory proteins is confirmed in vivo and in vitro. An antimalarial compound based on a hydroxyethylamine scaffold interrupts the lytic cycle of T. gondii at submicromolar concentration by targeting ASP3.<\/jats:p>","DOI":"10.7554\/elife.27480","type":"journal-article","created":{"date-parts":[[2017,9,12]],"date-time":"2017-09-12T07:00:16Z","timestamp":1505199616000},"source":"Crossref","is-referenced-by-count":98,"title":["A druggable secretory protein maturase of Toxoplasma essential for invasion and egress"],"prefix":"10.7554","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9158-9612","authenticated-orcid":true,"given":"Sunil Kumar","family":"Dogga","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1058-3620","authenticated-orcid":true,"given":"Budhaditya","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Department of 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