{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:56:08Z","timestamp":1787169368848,"version":"build-2736575974"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"48","license":[{"start":{"date-parts":[[2021,5,16]],"date-time":"2021-05-16T00:00:00Z","timestamp":1621123200000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01 GM114450"],"award-info":[{"award-number":["R01 GM114450"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Rifampicin (Rif) is an antibiotic that targets bacterial RNA polymerase (RNAP). The search for new antibiotics against proven targets is one approach to combat multidrug-resistant tuberculosis (TB), a global threat. Here, we characterized the effects of the antibiotic sorangicin A (Sor) on a Rif-resistant (Rif\n                    <jats:sup>R<\/jats:sup>\n                    ) RNAP found in clinically isolated Rif\n                    <jats:sup>R<\/jats:sup>\n                    strains. Sor binds in the same pocket and inhibits wild-type RNAP by the same mechanism as Rif. However, Sor inhibits Rif\n                    <jats:sup>R<\/jats:sup>\n                    RNAPs by a distinct mechanism, providing a new target for drug design. Intriguingly, Sor displays a better pharmacokinetic profile compared to rifamycins, which is important for development of inhibitors to treat TB patients suffering from comorbidities. These results inform approaches toward drug development against antibiotic-resistant targets.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2013706117","type":"journal-article","created":{"date-parts":[[2020,11,16]],"date-time":"2020-11-16T20:32:12Z","timestamp":1605558732000},"page":"30423-30432","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":45,"title":["The antibiotic sorangicin A inhibits promoter DNA unwinding in a\n                    <i>Mycobacterium tuberculosis<\/i>\n                    rifampicin-resistant RNA polymerase"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2669-3998","authenticated-orcid":false,"given":"Mirjana","family":"Lilic","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biophysics, The Rockefeller University, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2311-003X","authenticated-orcid":false,"given":"James","family":"Chen","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biophysics, The Rockefeller University, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hande","family":"Boyaci","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biophysics, The Rockefeller University, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6563-984X","authenticated-orcid":false,"given":"Nathaniel","family":"Braffman","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biophysics, The Rockefeller University, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Hubin","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biophysics, The Rockefeller University, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Department Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research, Saarland University, 66123 Saarbr\u00fccken, Germany;"},{"name":"Department of Pharmacy, Saarland University, 66123 Saarbr\u00fccken, Germany;"},{"name":"Partner Site Hannover-Braunschweig, German Center for Infection Research, 38124 Braunschweig, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1042-5665","authenticated-orcid":false,"given":"Rolf","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research, Saarland University, 66123 Saarbr\u00fccken, Germany;"},{"name":"Department of Pharmacy, Saarland University, 66123 Saarbr\u00fccken, Germany;"},{"name":"Partner Site Hannover-Braunschweig, German Center for Infection Research, 38124 Braunschweig, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Mooney","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5042-0383","authenticated-orcid":false,"given":"Robert","family":"Landick","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706;"},{"name":"Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biophysics, The Rockefeller University, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,11,16]]},"reference":[{"key":"e_1_3_4_1_2","unstructured":"World Health Organization Global Tuberculosis Report 2018 (World Health Organization 2018)."},{"key":"e_1_3_4_2_2","unstructured":"A. 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