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Medicinal-Pharmaceutical Chemistry Commons

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Physics and Astronomy Publications

2005

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Full-Text Articles in Medicinal-Pharmaceutical Chemistry

A Periplasmic Drug-Binding Site Of The Acrb Multidrug Efflux Pump: A Crystallographic And Site-Directed Mutagenesis Study, Edward Yu, Juilo R. Aires, Gerry Mcdermott, Hiroshi Nikaido Jan 2005

A Periplasmic Drug-Binding Site Of The Acrb Multidrug Efflux Pump: A Crystallographic And Site-Directed Mutagenesis Study, Edward Yu, Juilo R. Aires, Gerry Mcdermott, Hiroshi Nikaido

Physics and Astronomy Publications

The Escherichia coli AcrB multidrug efflux pump is a membrane protein that recognizes many structurally dissimilar toxic compounds. We previously reported the X-ray structures of four AcrB-ligand complexes in which the ligands were bound to the wall of the extremely large central cavity in the transmembrane domain of the pump. Genetic studies, however, suggested that discrimination between the substrates occurs mainly in the periplasmic domain rather than the transmembrane domain of the pump. We here describe the crystal structures of the AcrB mutant in which Asn109 was replaced by Ala, with five structurally diverse ligands, ethidium, rhodamine 6G, ciprofloxacin, nafcillin ...