Structure of MsbA from E. coli : A Homolog of the Multidrug Resistance ATP Binding Cassette (ABC) Transporters
- 7 September 2001
- journal article
- retracted article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 293 (5536), 1793-1800
- https://doi.org/10.1126/science.293.5536.1793
Abstract
Multidrug resistance (MDR) is a serious medical problem and presents a major challenge to the treatment of disease and the development of novel therapeutics. ABC transporters that are associated with multidrug resistance (MDR-ABC transporters) translocate hydrophobic drugs and lipids from the inner to the outer leaflet of the cell membrane. To better elucidate the structural basis for the “flip-flop” mechanism of substrate movement across the lipid bilayer, we have determined the structure of the lipid flippase MsbA from Escherichia coli by x-ray crystallography to a resolution of 4.5 angstroms. MsbA is organized as a homodimer with each subunit containing six transmembrane α-helices and a nucleotide-binding domain. The asymmetric distribution of charged residues lining a central chamber suggests a general mechanism for the translocation of substrate by MsbA and other MDR-ABC transporters. The structure of MsbA can serve as a model for the MDR-ABC transporters that confer multidrug resistance to cancer cells and infectious microorganisms.Keywords
This publication has 38 references indexed in Scilit:
- The crystal structure of a liganded trehalose/maltose-binding protein from the hyperthermophilic archaeon Thermococcus litoralis at 1.85 ÅJournal of Molecular Biology, 2001
- Structural Biology of Rad50 ATPaseCell, 2000
- ABC-ATPases, adaptable energy generators fuelling transmembrane movement of a variety of molecules in organisms from bacteria to humansJournal of Molecular Biology, 1999
- BIOCHEMICAL, CELLULAR, AND PHARMACOLOGICAL ASPECTS OF THE MULTIDRUG TRANSPORTERAnnual Review of Pharmacology and Toxicology, 1999
- The Structure of the Potassium Channel: Molecular Basis of K + Conduction and SelectivityScience, 1998
- The human MDR3 P‐glycoprotein promotes translocation of phosphatidylcholine through the plasma membrane of fibroblasts from transgenic miceFEBS Letters, 1994
- CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choiceNucleic Acids Research, 1994
- The CCP4 suite: programs for protein crystallographyActa Crystallographica Section D-Biological Crystallography, 1994
- Sequences encoded in the class II region of the MHC related to the 'ABC' superfamily of transportersNature, 1990
- Basic local alignment search toolJournal of Molecular Biology, 1990