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Antibiotic leads CBR9379 and AAP-SO\n                  <jats:sub>2<\/jats:sub>\n                  inhibit the\n                  <jats:italic>Escherichia coli<\/jats:italic>\n                  and\n                  <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                  RNAPs, respectively, by binding in a pocket formed by the bridge helix and RH-FL. The precise mechanism of action for these inhibitors is yet to be defined. We present cryo-electron microscopy structures showing that both compounds inhibit the RNAP NAC by preventing RH-FL closure, thereby allosterically destabilizing the closed TL. This work reveals a conserved mechanistic principle of RNAP catalysis across all domains of life and provides new insight for antibiotic design.\n                <\/jats:p>","DOI":"10.64898\/2026.04.06.716786","type":"posted-content","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T03:45:12Z","timestamp":1775619912000},"source":"Crossref","is-referenced-by-count":0,"title":["RNA polymerase inhibitors reveal active-site motions essential for the nucleotide-addition cycle"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9060-8201","authenticated-orcid":false,"given":"Yukti","family":"Dhingra","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biophysics, The Rockefeller University, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5042-0383","authenticated-orcid":false,"given":"Robert","family":"Landick","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Department of Bacteriology, University of Wisconsin-Madison, Wisconsin, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1332-128X","authenticated-orcid":false,"given":"Elizabeth A.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathogenesis, The Rockefeller University, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8241-3153","authenticated-orcid":false,"given":"Seth A.","family":"Darst","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biophysics, The Rockefeller University, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026040909550936000_2026.04.06.716786v1.1","doi-asserted-by":"crossref","unstructured":"J. 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