2J8S

Drug Export Pathway of Multidrug Exporter AcrB Revealed by DARPin Inhibitors

Summary for 2J8S

• Entry DOI: 10.2210/pdb2j8s/pdb
• Related: 1IWG 1OY6 1OY8 1OY9 1OYD 1OYE 1T9T 1T9U 1T9V 1T9W 1T9X 1T9Y 2GIF 2HRT
• Descriptor: ACRIFLAVINE RESISTANCE PROTEIN B, DARPIN, DODECYL-BETA-D-MALTOSIDE, ... (5 entities in total)
• Functional Keywords: membrane protein-complex, designed ankyrin repeat protein, multidrug resistance protein, co-crystallization, antibiotic resistance, inner membrane, protein complex, membrane protein, rnd, membrane, inhibitor, transport, transmembrane, drug-efflux pump, transport protein, antibiotic resistance-inhibitor complex
• Biological source: ESCHERICHIA COLI; More
• Total number of polymer chains: 5
• Total formula weight: 385733.97

Authors

Sennhauser, G.,Amstutz, P.,Briand, C.,Storchenegger, O.,Gruetter, M.G. (deposition date: 2006-10-27, release date: 2007-01-23, Last modification date: 2023-12-13)

Primary citation

Sennhauser, G.,Amstutz, P.,Briand, C.,Storchenegger, O.,Grutter, M.G.
Drug Export Pathway of Multidrug Exporter Acrb Revealed by Darpin Inhibitors.
Plos Biol., 5:E7-, 2007

PubMed Abstract: The multidrug exporter AcrB is the inner membrane component of the AcrAB-TolC drug efflux system in Escherichia coli and is responsible for the resistance of this organism to a wide range of drugs. Here we describe the crystal structure of the trimeric AcrB in complex with a designed ankyrin-repeat protein (DARPin) inhibitor at 2.5-A resolution. The three subunits of AcrB are locked in different conformations revealing distinct channels in each subunit. There seems to be remote conformational coupling between the channel access, exit, and the putative proton-translocation site, explaining how the proton motive force is used for drug export. Thus our structure suggests a transport pathway not through the central pore but through the identified channels in the individual subunits, which greatly advances our understanding of the multidrug export mechanism.

PubMed: 17194213
DOI: 10.1371/JOURNAL.PBIO.0050007

Experimental method

X-RAY DIFFRACTION (2.54 Å)