The translocation mechanism of P-glycoprotein

Richard Callaghan, Robert C. Ford, Ian D. Kerr

    Research output: Contribution to journalArticlepeer-review


    Multidrug transporters are involved in mediating the failure of chemotherapy in treating several serious diseases. The archetypal multidrug transporter P-glycoprotein (P-gp) confers resistance to a large number of chemically and functionally unrelated anti-cancer drugs by mediating efflux from cancer cells. The ability to efflux such a large number of drugs remains a biological enigma and the lack of mechanistic understanding of the translocation pathway used by P-gp prevents rational design of compounds to inhibit its function. The translocation pathway is critically dependent on ATP hydrolysis and drug interaction with P-gp is possible at one of a multitude of allosterically linked binding sites. However, aspects such as coupling stoichiometry, molecular properties of binding sites and the nature of conformational changes remain unresolved or the centre of considerable controversy. The present review attempts to utilise the available data to generate a detailed sequence of events in the translocation pathway for this dexterous protein. © 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
    Original languageEnglish
    Pages (from-to)1056-1063
    Number of pages7
    JournalFEBS Letters
    Issue number4
    Publication statusPublished - 13 Feb 2006


    • Drug-binding
    • Drug-protein interaction
    • Membrane transport
    • P-glycoprotein


    Dive into the research topics of 'The translocation mechanism of P-glycoprotein'. Together they form a unique fingerprint.

    Cite this