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A model of a transmembrane drug‐efflux pump from Gram‐negative bacteria
Author(s) -
Fernandez-Recio Juan,
Walas Fabien,
Federici Luca,
Venkatesh Pratap J.,
Bavro Vassiliy N.,
Miguel Ricardo Nunez,
Mizuguchi Kenji,
Luisi Ben
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.10.097
Subject(s) - periplasmic space , efflux , antiporter , escherichia coli , allosteric regulation , transmembrane protein , membrane transport protein , transport protein , bacteria , inner membrane , electrochemical gradient , bacterial outer membrane , transmembrane domain , biochemistry , membrane protein , biology , integral membrane protein , outer membrane efflux proteins , membrane , enzyme , genetics , receptor , gene
In Gram‐negative bacteria, drug resistance is due in part to the activity of transmembrane efflux‐pumps, which are composed of three types of proteins. A representative pump from Escherichia coli is an assembly of the trimeric outer‐membrane protein TolC, which is an allosteric channel, the trimeric inner‐membrane proton‐antiporter AcrB, and the periplasmic protein, AcrA. The pump displaces drugs vectorially from the bacterium using proton electrochemical force. Crystal structures are available for TolC and AcrB from E. coli , and for the AcrA homologue MexA from Pseudomonas aeruginosa . Based on homology modelling and molecular docking, we show how AcrA, AcrB and TolC might assemble to form a tripartite pump, and how allostery may occur during transport.