{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:09:44Z","timestamp":1790698184143,"version":"4.1.0"},"reference-count":47,"publisher":"American Chemical Society (ACS)","issue":"38","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005825","name":"National Institute of Food and Agriculture","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031478","name":"NextGenerationEU","doi-asserted-by":"publisher","award":["LX22NPO5103"],"award-info":[{"award-number":["LX22NPO5103"]}],"id":[{"id":"10.13039\/100031478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100025961","name":"European Union Studies Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100025961","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tuberculosis (TB) is again the world\u2019s leading cause of death from a single infectious agent. Aminoacyl-tRNA synthetases are essential for protein synthesis and are promising drug targets because bacterial and human enzymes differ. We repurposed a human prolyl-tRNA synthetase (ProRS) inhibitor scaffold, 3-aminopyrazine-2-carboxamide, to inhibit the Mycobacterium tuberculosis enzyme (MtbProRS). These derivatives show strong activity against multidrug-resistant Mtb strains and are not cytotoxic to HepG2 cells. We determined high-resolution crystal structures of MtbProRS bound to six derivatives to define their binding modes. The compounds bind in the ATP site and trigger local conformational changes that disrupt the proline pocket, supporting a dual-site mechanism of inhibition. Comparison with human cytosolic and mitochondrial ProRS reveals differences in active-site residues, electrostatics, and dynamics that explain species selectivity. Together, these structures provide a framework for designing next-generation, Mtb-selective ProRS inhibitors as new antitubercular candidates.<\/jats:p>","DOI":"10.1021\/acsomega.6c04844","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:02:08Z","timestamp":1789624928000},"page":"57583-57594","source":"Crossref","is-referenced-by-count":0,"title":["Atomic-Level Structures\nReveal How a Repurposed 3-Aminopyrazine-2-carboxamide\nScaffold Inhibits\n                    <i>Mycobacterium tuberculosis<\/i>\n                    Prolyl-tRNA Synthetase"],"prefix":"10.1021","volume":"11","author":[{"given":"Priyanka","family":"Gade","sequence":"first","affiliation":[{"name":"University of Chicago , , , ,","place":["Chicago, Illinois, United States, 60667"]},{"name":"Argonne National Laboratory , , , ,","place":["Lemont, Illinois, United States, 60439"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Michalska","sequence":"additional","affiliation":[{"name":"University of Chicago , , , ,","place":["Chicago, Illinois, United States, 60667"]},{"name":"Argonne National Laboratory , , , ,","place":["Lemont, Illinois, United States, 60439"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0104-9925","authenticated-orcid":true,"given":"Jan","family":"Zitko","sequence":"additional","affiliation":[{"name":"Charles University , , Ak. Heyrovske\u0301ho 1203\/8 , ,","place":["Hradec Kralove, Czech Republic, 500 03"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Wower","sequence":"additional","affiliation":[{"name":"Auburn University , , , ,","place":["Auburn, Alabama, United States, 36849"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Maltseva","sequence":"additional","affiliation":[{"name":"University of Chicago , , , ,","place":["Chicago, Illinois, United States, 60667"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod Sukanth Kumar","family":"Pallabothula","sequence":"additional","affiliation":[{"name":"Charles University , , Ak. Heyrovske\u0301ho 1203\/8 , ,","place":["Hradec Kralove, Czech Republic, 500 03"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Jedrzejczak","sequence":"additional","affiliation":[{"name":"University of Chicago , , , ,","place":["Chicago, Illinois, United States, 60667"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2535-6209","authenticated-orcid":true,"given":"Andrzej","family":"Joachimiak","sequence":"additional","affiliation":[{"name":"University of Chicago , , , ,","place":["Chicago, Illinois, United States, 60667"]},{"name":"Argonne National Laboratory , , , ,","place":["Lemont, Illinois, United States, 60439"]},{"name":"University of Chicago , , , ,","place":["Chicago, Illinois, United States, 60367"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"2026092911105672000_cit1","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1016\/S2213-2600(19)30263-2","article-title":"The Lancet Respiratory Medicine Commission: 2019 update:\nepidemiology, pathogenesis, transmission, diagnosis, and management\nof multidrug-resistant and incurable tuberculosis","volume":"7","author":"Dheda","year":"2019","journal-title":"Lancet Respir. 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