Journal ArticleDOI
Structure of MsbA from E. coli: A Homolog of the Multidrug Resistance ATP Binding Cassette (ABC) Transporters
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TLDR
The structure of MsbA can serve as a model for the MDR-ABC transporters that confer multidrug resistance to cancer cells and infectious microorganisms.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.read more
Citations
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ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins.
TL;DR: The quality scores of a protein are displayed in the context of all known protein structures and problematic parts of a structure are shown and highlighted in a 3D molecule viewer in the ProSA-web service.
Journal ArticleDOI
Molecular Basis of Bacterial Outer Membrane Permeability Revisited
TL;DR: This review summarizes the development in the field since the previous review and begins to understand how this bilayer of the outer membrane can retard the entry of lipophilic compounds, owing to increasing knowledge about the chemistry of lipopolysaccharide from diverse organisms and the way in which lipopoly Saccharide structure is modified by environmental conditions.
Journal ArticleDOI
Targeting multidrug resistance in cancer
Gergely Szakács,Jill K. Paterson,Joseph A. Ludwig,Catherine Booth-Genthe,Michael M. Gottesman +4 more
TL;DR: Various approaches to combating multidrug-resistant cancer are described, including the development of drugs that engage, evade or exploit efflux by ABC transporters.
Journal ArticleDOI
Drug Resistance in Cancer: An Overview
Genevieve Housman,Shannon Byler,Sarah Heerboth,Karolina Lapinska,Mckenna Longacre,Nicole A. Snyder,Sibaji Sarkar +6 more
TL;DR: The current knowledge of mechanisms that promote or enable drug resistance, such as drug inactivation, drug target alteration, drug efflux, DNA damage repair, cell death inhibition, and the epithelial-mesenchymal transition, as well as how inherent tumor cell heterogeneity plays a role in drug resistance are outlined.
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Mammalian ABC Transporters in Health and Disease
Piet Borst,R.P.J. Oude Elferink +1 more
TL;DR: This work focuses on three topics: ABC transporters transporting drugs (xenotoxins) and drug conjugates, and a rapidly increasing number of ABC Transporters found to play a role in lipid transport.
References
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The Structure of the Potassium Channel: Molecular Basis of K+ Conduction and Selectivity
Declan A. Doyle,João H.Morais Cabral,Richard A. Pfuetzner,Anling Kuo,Jacqueline M. Gulbis,Steven L. Cohen,Brian T. Chait,Roderick MacKinnon +7 more
TL;DR: The architecture of the pore establishes the physical principles underlying selective K+ conduction, which promotes ion conduction by exploiting electrostatic repulsive forces to overcome attractive forces between K+ ions and the selectivity filter.