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Structure of MsbA from E. coli : A Homolog of the Multidrug Resistance ATP Binding Cassette (ABC) Transporters
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.
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Altschul, S. F., Gish, W., Miller, W., Myers, E. W., & Lipman, D. J. (1990) · Journal of Molecular Biology · doi:10.1006/jmbi.1990.9999 · Cited by 98,669
Cited by
Wiederstein, M., & Sippl, M. J. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm290 · Cited by 5,909
Raetz, C. R. H., & Whitfield, C. (2002) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.71.110601.135414 · Cited by 4,404
Molecular Basis of Bacterial Outer Membrane Permeability Revisited
Nikaido, H. (2003) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.67.4.593-656.2003 · Cited by 4,316
Targeting multidrug resistance in cancer
Szakács, G., Paterson, J. K., Ludwig, J. A., Booth-Genthe, C., & Gottesman, M. M. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd1984 · Cited by 3,609
Drug resistance in cancer: An overview
Housman, G., Byler, S., Heerboth, S., Lapinska, K., Longacre, M., Snyder, N., & Sarkar, S. (2014) · Cancers · doi:10.3390/cancers6031769 · Cited by 2,463
Metadata
- Authors
- Chang, G., & Roth, C. B.
- Venue
- Science
- Published
- 2001-09-07
- Volume
- 293
- Issue
- 5536
- Pages
- 1793-1800
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2094303590
- Cited by
- 619
- References
- 1
- FWCI
- 39.48
- Type
- journal article
- Language
- en
- Status
- Retracted
- Open access
- closed
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- Chang, G., & Roth, C. B. (2001). Structure of MsbA from E. coli : A Homolog of the Multidrug Resistance ATP Binding Cassette (ABC) Transporters. Science. https://doi.org/10.1126/science.293.5536.1793
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
