Structural and dynamic perspectives on the promiscuous transport activity of P-glycoprotein

Nandhitha Subramanian, Karmen Condic-Jurkic, Megan L. O'Mara*

*Corresponding author for this work

    Research output: Contribution to journalReview articlepeer-review

    39 Citations (Scopus)

    Abstract

    The multidrug transporter P-glycoprotein (P-gp) is expressed in the blood-brain barrier endothelium where it effluxes a range of drug substrates, preventing their accumulation within the brain. P-gp has been studied extensively for 40 years because of its crucial role in the absorption, distribution, metabolism and elimination of a range of pharmaceutical compounds. Despite this, many aspects of the structure-function mechanism of P-gp are unresolved. Here we review the emerging role of molecular dynamics simulation techniques in our understanding of the membrane-embedded conformation of P-gp. We discuss its conformational plasticity in the presence and absence of ATP, and recent efforts to characterize the drug binding sites and uptake pathways.

    Original languageEnglish
    Pages (from-to)146-152
    Number of pages7
    JournalNeurochemistry International
    Volume98
    DOIs
    Publication statusPublished - 1 Sept 2016

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