{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:25:18Z","timestamp":1790166318458,"version":"4.1.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2012,7,6]],"date-time":"2012-07-06T00:00:00Z","timestamp":1341532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,7,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tripartite complex AcrB\u2013ToIC, the major efflux system in Escherichia coli, is the principal multidrug transporter in Gram-negative bacteria, which is important in antibiotic drug tolerance. AcrB is a homotrimer that acts as a tripartite complex with the outer membrane channel ToIC and the membrane fusion protein AcrA. Recently, the crystal structures of AcrB bound to the high-molecular-mass drugs rifampicin and erythromycin were reported. Here we performed 20 ns molecular dynamics (MD) simulations of the AcrB\u2013rifampicin\u2013minocycline complex in a lipid bilayer and explicit water. We found that the bound drugs, rifampicin and erythromycin, made a unidirectional peristaltic movement towards the extrusion funnel of ToIC, which was facilitated by the water efflux in the channel of AcrB. With a shift of the Phe-617 loop, rifampicin in the access monomer moved towards the entrance of the distal binding pocket. Minocycline in the binding monomer moved from the distal binding pocket towards the gate of the central funnel. The channel between the entrance and the gate made a concerted opening during the MD simulations, which was helpful for the peristaltic movement. Our results showed that the mutations of Gly616Pro and Gly619Pro prevented the movement of the Phe-617 loop, which indicated the critical role of the flexibility of the Phe-617 loop. In addition, three putative proton translocation channels were proposed based on our results. Our study provided dynamical information and important residues for the peristaltic movement in AcrB, which were critical for substrate uptake and extrusion function.<\/jats:p>\n                  <jats:p\/>","DOI":"10.1039\/c2mb25184a","type":"journal-article","created":{"date-parts":[[2012,7,7]],"date-time":"2012-07-07T04:34:00Z","timestamp":1341635640000},"page":"2699-2709","source":"Crossref","is-referenced-by-count":28,"title":["Unidirectional peristaltic movement in multisite drug binding pockets of AcrB from molecular dynamics simulations"],"prefix":"10.1093","volume":"8","author":[{"given":"Zhiwei","family":"Feng","sequence":"first","affiliation":[{"name":"Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University a , Suzhou, Jiangsu 215123, China yyli@suda.edu.cn"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingjun","family":"Hou","sequence":"additional","affiliation":[{"name":"Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University a , Suzhou, Jiangsu 215123, China yyli@suda.edu.cn"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youyong","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University a , Suzhou, Jiangsu 215123, China yyli@suda.edu.cn"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,7,6]]},"reference":[{"key":"2026012913063122000_cit1","doi-asserted-by":"crossref","first-page":"8278","DOI":"10.1021\/jp200996x","article-title":"Role of Water during the Extrusion of Substrates by the Efflux Transporter AcrB","volume":"115","author":"Schulz","year":"2011","journal-title":"J. Phys. Chem. B"},{"key":"2026012913063122000_cit2","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1128\/jb.178.1.306-308.1996","article-title":"AcrAB efflux pump plays a major role in the antibiotic resistance phenotype of Escherichia coli multiple-antibiotic-resistance (Mar) mutants","volume":"178","author":"Okusu","year":"1996","journal-title":"J. Bacteriol."},{"key":"2026012913063122000_cit3","doi-asserted-by":"crossref","first-page":"5803","DOI":"10.1128\/JB.183.20.5803-5812.2001","article-title":"Analysis of a complete library of putative drug transporter genes in Escherichia coli","volume":"183","author":"Nishino","year":"2001","journal-title":"J. Bacteriol."},{"key":"2026012913063122000_cit4","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/0966-842X(94)90654-8","article-title":"Efflux pumps and drug resistance in gram-negative bacteria","volume":"2","author":"Ma","year":"1994","journal-title":"Trends Microbiol."},{"key":"2026012913063122000_cit5","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1006\/jmbi.2000.3961","article-title":"Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes","volume":"301","author":"Paulsen","year":"2000","journal-title":"J. Mol. Biol."},{"key":"2026012913063122000_cit6","first-page":"255","article-title":"Multidrug efflux pumps and antimicrobial resistance in Pseudomonas aeruginosa and related organisms","volume":"3","author":"Poole","year":"2001","journal-title":"J. Mol. Microbiol. Biotechnol."},{"key":"2026012913063122000_cit7","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1111\/j.1365-2958.2005.04940.x","article-title":"Virulence and drug resistance roles of multidrug efflux systems of Salmonella enterica serovar Typhimurium","volume":"59","author":"Nishino","year":"2006","journal-title":"Mol. Microbiol."},{"key":"2026012913063122000_cit8","doi-asserted-by":"crossref","first-page":"729","DOI":"10.2174\/138945008785747789","article-title":"The AcrB efflux pump: conformational cycling and peristalsis lead to multidrug resistance","volume":"9","author":"Seeger","year":"2008","journal-title":"Curr. Drug Targets"},{"key":"2026012913063122000_cit9","doi-asserted-by":"crossref","first-page":"e1000806","DOI":"10.1371\/journal.pcbi.1000806","article-title":"Functional rotation of the transporter AcrB: insights into drug extrusion from simulations","volume":"6","author":"Schulz","year":"2010","journal-title":"PLoS Comput. 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Chem."},{"key":"2026012913063122000_cit13","doi-asserted-by":"crossref","first-page":"7173","DOI":"10.1073\/pnas.0900693106","article-title":"The assembled structure of a complete tripartite bacterial multidrug efflux pump","volume":"106","author":"Symmons","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026012913063122000_cit14","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1038\/35016007","article-title":"Crystal structure of the bacterial membrane protein TolC central to multidrug efflux and protein export","volume":"405","author":"Koronakis","year":"2000","journal-title":"Nature"},{"key":"2026012913063122000_cit15","doi-asserted-by":"crossref","first-page":"5803","DOI":"10.1128\/jb.178.19.5803-5805.1996","article-title":"Evidence that TolC is required for functioning of the Mar\/AcrAB efflux pump of Escherichia coli","volume":"178","author":"Fralick","year":"1996","journal-title":"J. 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Biol."},{"key":"2026012913063122000_cit18","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.str.2005.11.015","article-title":"Conformational flexibility in the multidrug efflux system protein AcrA","volume":"14","author":"Mikolosko","year":"2006","journal-title":"Structure"},{"key":"2026012913063122000_cit19","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/nature01050","article-title":"Crystal structure of bacterial multidrug efflux transporter AcrB","volume":"419","author":"Murakami","year":"2002","journal-title":"Nature"},{"key":"2026012913063122000_cit20","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.sbi.2008.06.007","article-title":"Multidrug efflux transporter, AcrB \u2013 the pumping mechanism","volume":"18","author":"Murakami","year":"2008","journal-title":"Curr. Opin. Struct. 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Acta, Bioenerg."},{"key":"2026012913063122000_cit47","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1002\/cphc.200600128","article-title":"Proton transfer 200 years after von Grotthuss: insights from ab initio simulations","volume":"7","author":"Marx","year":"2006","journal-title":"ChemPhysChem"},{"key":"2026012913063122000_cit48","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1007\/s00424-008-0503-8","article-title":"Protons and how they are transported by proton pumps","volume":"457","author":"Buch-Pedersen","year":"2009","journal-title":"Pflugers Arch."}],"container-title":["Molecular BioSystems"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/molecular-omics\/article-pdf\/8\/10\/2699\/66151494\/c2mb25184a.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/molecular-omics\/article-pdf\/8\/10\/2699\/66151494\/c2mb25184a.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T18:09:05Z","timestamp":1769710145000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/molecular-omics\/article\/8\/10\/2699\/8348347"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,7,6]]},"references-count":48,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2012,7,6]]}},"URL":"https:\/\/doi.org\/10.1039\/c2mb25184a","relation":{},"ISSN":["1742-2051","1742-206X"],"issn-type":[{"value":"1742-2051","type":"electronic"},{"value":"1742-206X","type":"print"}],"subject":[],"published-other":{"date-parts":[[2012,10,1]]},"published":{"date-parts":[[2012,7,6]]}}}