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The apicomplexan PRSs are validated targets of febrifugine (FF) and its halogenated derivative halofuginone (HF). PRSs are of great interest for drug development against <jats:italic>Plasmodium falciparum<\/jats:italic> and <jats:italic>Toxoplasma gondii<\/jats:italic>. In this study, structures of apo and FF-bound <jats:italic>T. gondii<\/jats:italic> (<jats:italic>Tg<\/jats:italic>PRS) are revealed and the dynamic nature of the conformational changes that occur upon FF binding is unraveled. In addition, this study highlights significant conformational plasticity within two different crystal structures of apo PRSs but not within drug-bound PRSs. The apo PRSs exist in multi-conformational states and manifest pseudo-dimeric structures. In contrast, when FF is bound the PRS dimer adopts a highly symmetrical architecture. It is shown that <jats:italic>Tg<\/jats:italic>PRS does not display extant fold switching, in contrast to <jats:italic>P.\u00a0falciparum<\/jats:italic> PRS, despite having over 65% sequence identity. Finally, structure-comparison analyses suggest the utility of r.m.s.d. per residue (r.m.s.d.<jats:sup>\/res<\/jats:sup>) as a robust tool to detect structural alterations even when the r.m.s.d. is low. Apo <jats:italic>Tg<\/jats:italic>PRS reveals FF\/HF-induced rigidity and this work has implications for drug-design studies that rely on the apo structures of target proteins.<\/jats:p>","DOI":"10.1107\/s2053230x19014808","type":"journal-article","created":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T14:25:02Z","timestamp":1573136702000},"page":"714-724","update-policy":"https:\/\/doi.org\/10.1107\/cm_01","source":"Crossref","is-referenced-by-count":13,"title":["Conformational heterogeneity in apo and drug-bound structures of <i>Toxoplasma gondii<\/i> prolyl-tRNA synthetase"],"prefix":"10.1107","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0907-9256","authenticated-orcid":true,"given":"Siddhartha","family":"Mishra","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nipun","family":"Malhotra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shreya","family":"Kumari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mizuki","family":"Sato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruhisa","family":"Kikuchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manickam","family":"Yogavel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3305-0034","authenticated-orcid":true,"given":"Amit","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"329","published-online":{"date-parts":[[2019,11,7]]},"reference":[{"key":"ow5017_bb1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1107\/S0907444909052925","volume":"66","author":"Adams","year":"2010","journal-title":"Acta Cryst. 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