Towards understanding promiscuity in multidrug efflux pumps

Trends Biochem Sci. 2014 Jan;39(1):8-16. doi: 10.1016/j.tibs.2013.11.002. Epub 2013 Dec 6.


Drug export from cells is a major factor in the acquisition of cellular resistance to antimicrobial and cancer chemotherapy, and poses a significant threat to future clinical management of disease. Many of the proteins that catalyse drug efflux do so with remarkably low substrate specificity, a phenomenon known as multidrug transport. For these reasons we need a greater understanding of drug recognition and transport in multidrug pumps to inform research that attempts to circumvent their action. Structural and computational studies have been heralded as being great strides towards a full elucidation of multidrug recognition and transport. In this review we summarise these advances and ask how close we are to a molecular understanding of this remarkable phenomenon.

Keywords: ABC transporter; MATE transporter; MFS transporter; P-glycoprotein.; RND transporter; SMR transporter; antibiotic resistance; chemotherapy; drug resistance.

Publication types

  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / antagonists & inhibitors
  • ATP-Binding Cassette Transporters / chemistry
  • ATP-Binding Cassette Transporters / physiology*
  • Animals
  • Bacterial Outer Membrane Proteins / antagonists & inhibitors
  • Bacterial Outer Membrane Proteins / chemistry
  • Bacterial Outer Membrane Proteins / physiology*
  • Biological Transport
  • Drug Resistance, Bacterial
  • Drug Resistance, Neoplasm
  • Humans
  • Models, Molecular
  • Protein Conformation


  • ATP-Binding Cassette Transporters
  • Bacterial Outer Membrane Proteins