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lüll The remarkable transport mechanism of P-glycoprotein: a multidrug transporter Al-Shawi MK; Omote HJ Bioenerg Biomembr 2005[Dec]; 37 (6): 489-96Human 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.|ATP Binding Cassette Transporter, Subfamily B, Member 1/*chemistry/metabolism[MESH]|Biological Transport[MESH]|Electron Spin Resonance Spectroscopy[MESH]|Humans[MESH]|Kinetics[MESH]|Models, Chemical[MESH]|Thermodynamics[MESH] |