The remarkable transport mechanism of P-glycoprotein: A multidrug transporter

Marwan K. Al-Shawi, Hiroshi Omote

Research output: Contribution to journalReview articlepeer-review

63 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)489-496
Number of pages8
JournalJournal of Bioenergetics and Biomembranes
Issue number6
Publication statusPublished - Dec 2005


  • EPR
  • Energy coupling
  • Heterologous expression
  • Homology modeling
  • Kinetics
  • Mechanism
  • Multidrug resistance
  • P-glycoprotein
  • Thermodynamics
  • Transporter

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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