Caister Academic Press

Structure-function Relationships in ABC Multidrug Transporters

Daniel A. P. Gutmann and Hendrik W. van Veen
from: ABC Transporters in Microorganisms: Research, Innovation and Value as Targets against Drug Resistance (Edited by: Alicia Ponte-Sucre). Caister Academic Press, U.K. (2009)


Investigations on ATP binding cassette (ABC) transporters have not only been an academic pursuit; these membrane transporters are central to many inherited disorders and are associated with multidrug resistance in cancer cells and pathogenic microorganisms. ABC multidrug transporters are capable of exporting a vast number of structurally unrelated compounds. Quantitative structure-activity relationship (QSAR) analyses of transported substrates, site-directed mutagenesis and use of thiol-reactive or photo-activatable drug analogues have provided useful information regarding the determinants of drug binding by ABC transporters. Recent studies on MsbA from Escherichia coli indicated that residues important for drug selectivity are located in the membrane domains of the transporter close to the leaflet-leaflet interface of the phospholipid bilayer. These and other insights in substrate binding, substrate translocation and energy-coupling by ABC extrusion systems will be reviewed read more ...
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