KOPS - Das Institutionelle Repositorium der Universität Konstanz

Transport of drugs by the multidrug transporter AcrB involves an access and a deep binding pocket that are separated by a switch-loop

Transport of drugs by the multidrug transporter AcrB involves an access and a deep binding pocket that are separated by a switch-loop

Zitieren

Dateien zu dieser Ressource

Prüfsumme: MD5:89d55b3211e9dc09eebed98f01620d22

EICHER, Thomas, Hi-jea CHA, Markus A. SEEGER, Lorenz BRANDSTÄTTER, Jasmin EL-DELIK, Jürgen A. BOHNERT, Winfried V. KERN, François VERREY, Markus G. GRÜTTER, Kay DIEDERICHS, Klaas M. POS, 2012. Transport of drugs by the multidrug transporter AcrB involves an access and a deep binding pocket that are separated by a switch-loop. In: Proceedings of the National Academy of Sciences. 109(15), pp. 5687-5692. ISSN 0027-8424. eISSN 1091-6490

@article{Eicher2012-04-10Trans-20810, title={Transport of drugs by the multidrug transporter AcrB involves an access and a deep binding pocket that are separated by a switch-loop}, year={2012}, doi={10.1073/pnas.1114944109}, number={15}, volume={109}, issn={0027-8424}, journal={Proceedings of the National Academy of Sciences}, pages={5687--5692}, author={Eicher, Thomas and Cha, Hi-jea and Seeger, Markus A. and Brandstätter, Lorenz and El-Delik, Jasmin and Bohnert, Jürgen A. and Kern, Winfried V. and Verrey, François and Grütter, Markus G. and Diederichs, Kay and Pos, Klaas M.} }

<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/20810"> <dcterms:abstract xml:lang="eng">AcrAB-TolC is the major efflux protein complex in Escherichia coli extruding a vast variety of antimicrobial agents from the cell. The inner membrane component AcrB is a homotrimer, and it has been postulated that the monomers cycle consecutively through three conformational stages designated loose (L), tight (T), and open (O) in a concerted fashion. Binding of drugs has been shown at a periplasmic deep binding pocket in the T conformation. The initial drug-binding step and transport toward this drug-binding site has been elusive thus far. Here we report high resolution structures (1.9–2.25 Å) of AcrB/designed ankyrin repeat protein (DARPin) complexes with bound minocycline or doxorubicin. In the AcrB/doxorubicin cocrystal structure, binding of three doxorubicin molecules is apparent, with one doxorubicin molecule bound in the deep binding pocket of the T monomer and two doxorubicin molecules in a stacked sandwich arrangement in an access pocket at the lateral periplasmic cleft of the L monomer. This access pocket is separated from the deep binding pocket apparent in the T monomer by a switch-loop. The localization and conformational flexibility of this loop seems to be important for large substrates, because a G616N AcrB variant deficient in macrolide transport exhibits an altered conformation within this loop region. Transport seems to be a stepwise process of initial drug uptake in the access pocket of the L monomer and subsequent accommodation of the drug in the deep binding pocket during the L to T transition to the internal deep binding pocket of the T monomer.</dcterms:abstract> <dc:contributor>Grütter, Markus G.</dc:contributor> <dc:contributor>Bohnert, Jürgen A.</dc:contributor> <dc:contributor>Brandstätter, Lorenz</dc:contributor> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2012-11-07T09:51:21Z</dcterms:available> <dc:contributor>Pos, Klaas M.</dc:contributor> <dc:contributor>Eicher, Thomas</dc:contributor> <dc:creator>Grütter, Markus G.</dc:creator> <dc:creator>Bohnert, Jürgen A.</dc:creator> <dc:contributor>Verrey, François</dc:contributor> <dc:contributor>Cha, Hi-jea</dc:contributor> <dc:contributor>Seeger, Markus A.</dc:contributor> <dc:creator>Eicher, Thomas</dc:creator> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2012-11-07T09:51:21Z</dc:date> <dc:creator>Pos, Klaas M.</dc:creator> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/20810"/> <dc:creator>Verrey, François</dc:creator> <dc:contributor>El-Delik, Jasmin</dc:contributor> <dcterms:title>Transport of drugs by the multidrug transporter AcrB involves an access and a deep binding pocket that are separated by a switch-loop</dcterms:title> <dc:creator>Cha, Hi-jea</dc:creator> <dc:contributor>Diederichs, Kay</dc:contributor> <dcterms:issued>2012-04-10</dcterms:issued> <dc:rights>deposit-license</dc:rights> <dc:creator>Seeger, Markus A.</dc:creator> <dc:language>eng</dc:language> <dc:contributor>Kern, Winfried V.</dc:contributor> <dc:creator>Diederichs, Kay</dc:creator> <dc:creator>Kern, Winfried V.</dc:creator> <dc:creator>El-Delik, Jasmin</dc:creator> <dcterms:rights rdf:resource="http://nbn-resolving.org/urn:nbn:de:bsz:352-20140905103605204-4002607-1"/> <dcterms:bibliographicCitation>PNAS : Proceedings of the National Academy of Sciences of the United States of America ; 109 (2012), 15. - S. 5687-5692</dcterms:bibliographicCitation> <dc:creator>Brandstätter, Lorenz</dc:creator> </rdf:Description> </rdf:RDF>

Dateiabrufe seit 01.10.2014 (Informationen über die Zugriffsstatistik)

Diederichs 208108.pdf 176

Das Dokument erscheint in:

KOPS Suche


Stöbern

Mein Benutzerkonto