A model of a transmembrane drug‐efflux pump from Gram‐negative bacteria
- 18 November 2004
- journal article
- Published by Wiley in FEBS Letters
- Vol. 578 (1-2), 5-9
- https://doi.org/10.1016/j.febslet.2004.10.097
Abstract
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.Keywords
This publication has 34 references indexed in Scilit:
- AcrA, AcrB, and TolC of Escherichia coli Form a Stable Intermembrane Multidrug Efflux ComplexJournal of Biological Chemistry, 2004
- Assembly of the MexAB-OprM Multidrug Efflux System of Pseudomonas aeruginosa : Identification and Characterization of Mutations in mexA Compromising MexA Multimerization and Interaction with MexBJournal of Bacteriology, 2004
- Crystallographic analysis of AcrBFEBS Letters, 2004
- Identification of Protein–Protein Interaction Sites from Docking Energy LandscapesJournal of Molecular Biology, 2003
- Structural Basis of Multiple Drug-Binding Capacity of the AcrB Multidrug Efflux PumpScience, 2003
- Modeller: Generation and Refinement of Homology-Based Protein Structure ModelsMethods in Enzymology, 2003
- It takes three to tangoNature Biotechnology, 2002
- FUGUE: sequence-structure homology recognition using environment-specific substitution tables and structure-dependent gap penalties11Edited by B. HonigJournal of Molecular Biology, 2001
- Alignment and structure prediction of divergent protein families: periplasmic and outer membrane proteins of bacterial efflux pumpsJournal of Molecular Biology, 1999
- Assessment of protein models with three-dimensional profilesNature, 1992