A structure-based mechanism for drug binding by multidrug transporters

Trends Biochem Sci. 2000 Feb;25(2):39-43. doi: 10.1016/s0968-0004(99)01514-5.


Multidrug transporters bind chemically dissimilar, potentially cytotoxic compounds and remove them from the cell. How these transporters carry out either of these functions is unknown. On the basis of crystal structures of the multidrug-binding domain of the transcription activator BmrR and mutagenesis studies on the bacterial multidrug transporter MdfA, we propose a possible mechanism for the binding of cationic lipophilic drugs by multidrug transporters. The key element of this mechanism includes a conformational change in the transporter that exposes a buried charged residue in the substrate-binding pocket and allows access to this site by only those drugs that are its steric and electrostatic complements.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / chemistry
  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism*
  • Drug Resistance, Microbial
  • Drug Resistance, Multiple / physiology
  • Escherichia coli Proteins*
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism*
  • Membrane Transport Proteins*
  • Models, Molecular
  • Molecular Sequence Data
  • Pharmaceutical Preparations / metabolism*
  • Trans-Activators / chemistry
  • Trans-Activators / metabolism


  • ATP Binding Cassette Transporter, Subfamily B
  • Bacterial Proteins
  • BmrR protein, bacteria
  • Carrier Proteins
  • Escherichia coli Proteins
  • Mdfa protein, E coli
  • Membrane Proteins
  • Membrane Transport Proteins
  • Pharmaceutical Preparations
  • Trans-Activators