A model of a transmembrane drug-efflux pump from Gram-negative bacteria

FEBS Lett. 2004 Dec 3;578(1-2):5-9. doi: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Outer Membrane Proteins / chemistry
  • Bacterial Outer Membrane Proteins / metabolism
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism
  • Drug Resistance, Microbial
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / metabolism
  • Gram-Negative Bacteria / physiology*
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism
  • Membrane Transport Proteins / chemistry*
  • Membrane Transport Proteins / metabolism*
  • Models, Biological*
  • Models, Molecular
  • Multidrug Resistance-Associated Proteins
  • Protein Conformation

Substances

  • AcrB protein, E coli
  • Bacterial Outer Membrane Proteins
  • Carrier Proteins
  • Escherichia coli Proteins
  • Membrane Proteins
  • Membrane Transport Proteins
  • MexA protein, Pseudomonas aeruginosa
  • Multidrug Resistance-Associated Proteins
  • tolC protein, E coli