NDLI: New Insights into the Drug Binding, Transport and Lipid Flippase Activities of the P-Glycoprotein Multidrug Transporter

Content Provider	Springer Nature Link
Author	Sharom, Frances J. Lugo, Miguel R. Eckford, Paul D. W.
Copyright Year	2005
Abstract	The MDR1 P-glycoprotein, an ATP-binding cassette (ABC) superfamily member that functions as an ATP-driven drug efflux pump, has been linked to resistance of human tumors to multiple chemotherapeutic agents. P-glycoprotein binds and actively transports a large variety of hydrophobic drugs and peptides. P-glycoprotein in reconstituted proteoliposomes is also an outwardly directed flippase for membrane phospholipids and simple glycosphinglipids. This review focuses on recent advances in our understanding of P-glycoprotein structure and function, particularly through the use of fluorescence spectroscopic approaches. Progress is being made towards understanding the structure of the transporter, especially the spatial relationship between the two nucleotide-binding domains. Exploration of the P-glycoprotein catalytic cycle using vanadate-trapped complexes has revealed that drug transport likely takes place by concerted conformational changes linked to relaxation of a high energy intermediate. Low resolution mapping of the protein using fluorescence resonance energy transfer showed that both the H and R drug-binding sites are located within the cytoplasmic leaflet. Two drugs can bind to the R-site simultaneously, suggesting that the protein contains a large flexible binding region.
Starting Page	481
Ending Page	487
Page Count	7
File Format	PDF
ISSN	0145479X
Journal	Journal of Bioenergetics and Biomembranes
Volume Number	37
Issue Number	6
e-ISSN	15736881
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	2005-01-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	ABC transporter P-glycoprotein MDR1 multidrug resistance reconstitution lipid bilayers fluorescence spectroscopy drug binding lipid flippase glycosphingolipid Organic Chemistry Biochemistry Animal Biochemistry Animal Anatomy / Morphology / Histology Bioorganic Chemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Physiology

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