Title |
The Remarkable Transport Mechanism of P-Glycoprotein: A Multidrug Transporter
|
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Published in |
Journal of Bioenergetics and Biomembranes, December 2005
|
DOI | 10.1007/s10863-005-9497-5 |
Pubmed ID | |
Authors |
Marwan K. Al-Shawi, Hiroshi Omote |
Abstract |
Human P-glycoprotein (ABCB1) is a primary multidrug transporter located in plasma membranes, that utilizes the energy of ATP hydrolysis to pump toxic xenobiotics out of cells. P-glycoprotein employs a most unusual molecular mechanism to perform this drug transport function. Here we review our work to elucidate the molecular mechanism of drug transport by P-glycoprotein. High level heterologous expression of human P-glycoprotein, in the yeast Saccharomyces cerevisiae, has facilitated biophysical studies in purified proteoliposome preparations. Development of novel spin-labeled transport substrates has allowed for quantitative and rigorous measurements of drug transport in real time by EPR spectroscopy. We have developed a new drug transport model of P-glycoprotein from the results of mutagenic, quantitative thermodynamic and kinetic studies. This model satisfactorily accounts for most of the unusual kinetic, coupling, and physiological features of P-glycoprotein. Additionally, an atomic detail structural model of P-glycoprotein has been devised to place our results within a proper structural context. |
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Researcher | 7 | 12% |
Student > Master | 7 | 12% |
Student > Doctoral Student | 5 | 9% |
Other | 11 | 19% |
Unknown | 3 | 5% |
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Pharmacology, Toxicology and Pharmaceutical Science | 2 | 4% |
Other | 7 | 12% |
Unknown | 3 | 5% |