Multidrug transport by ATP binding cassette transporters: a proposed two-cylinder engine mechanism.
The elevated expression of ATP binding cassette (ABC) multidrug transporters in multidrug-resistant cells interferes with the drug-based control of cancers and infectious pathogenic microorganisms. Multidrug transporters interact directly with the drug substrates. This review summarizes current insights into the mechanism(s) by which ATP hydrolysis is coupled to drug transport in bacterial LmrA and its human homolog P-glycoprotein. In addition, the relevance of these insights for other ABC transporters will be discussed.
van Veen
H W
HW
Department of Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Haren, The Netherlands. hwv20@cam.ac.uk
Higgins
C F
CF
Konings
W N
WN
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000737:chemistry / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D013329:Structure-Activity Relationship
D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C101824:LmrA protein, Lactococcus lactis