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The\n                    <jats:italic>E. coli<\/jats:italic>\n                    AcrAB-TolC drug efflux pump contains the inner membrane H\n                    <jats:sup>+<\/jats:sup>\n                    \/drug antiporter AcrB comprising three functionally interdependent protomers, cycling consecutively through the loose (L), tight (T) and open (O) state during cooperative catalysis. Here, we present 13 X-ray structures of AcrB in intermediate states of the transport cycle. Structure-based mutational analysis combined with drug susceptibility assays indicate that drugs are guided through dedicated transport channels toward the drug binding pockets. A co-structure obtained in the combined presence of erythromycin, linezolid, oxacillin and fusidic acid shows binding of fusidic acid deeply inside the T protomer transmembrane domain. Thiol cross-link substrate protection assays indicate that this transmembrane domain-binding site can also accommodate oxacillin or novobiocin but not erythromycin or linezolid. AcrB-mediated drug transport is suggested to be allosterically modulated in presence of multiple drugs.\n                  <\/jats:p>","DOI":"10.1038\/s41467-021-24151-3","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T06:06:39Z","timestamp":1624946799000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":88,"title":["Allosteric drug transport mechanism of multidrug transporter AcrB"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7894-1957","authenticated-orcid":false,"given":"Heng-Keat","family":"Tam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2402-7729","authenticated-orcid":false,"given":"Wuen Ee","family":"Foong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Oswald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Herrmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9035-3827","authenticated-orcid":false,"given":"Klaas M.","family":"Pos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,29]]},"reference":[{"key":"24151_CR1","doi-asserted-by":"publisher","unstructured":"Krishnamoorthy, G. et al. 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