The structure and function of drug pumps: an update.
Our understanding of the exact mechanisms used by the transmembrane protein pumps that confer cellular resistance to cytotoxic drugs has improved enormously with the recent determination of the structures of three Escherichia coli transporters, two belonging to the ATP-binding cassette (ABC) superfamily and one to the resistance-nodulation-cell division (RND) family. Although these studies do not provide an insight into how drug pumps can recognize several structurally unrelated drugs, important advances have been also made in this area. Information on the molecular basis of multidrug recognition has been provided by determining the structure of transcriptional regulators that can bind, often structurally unrelated, cytotoxic drugs and control the expression of drug pumps.
McKeegan
Kenneth S
KS
Centre for Infectious Diseases, Wolfson Research Institute, Queen's Campus, University of Durham, Stockton-on-Tees, UK.
Borges-Walmsley
M Ines
MI
Walmsley
Adrian R
AR
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D001693:Biological Transport, Active; D002352:Carrier Proteins; D024881:Drug Resistance, Bacterial; D018432:Drug Resistance, Multiple; D029968:Escherichia coli Proteins; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C083496:AcrB protein, E coli; C101824:LmrA protein, Lactococcus lactis; C096807:LmrP protein, Lactococcus lactis