Recent Progress in Understanding the Mechanism of P-Glycoprotein-mediated Drug Efflux
- Cite this article as:
- Loo, T. & Clarke, D. J Membrane Biol (2005) 206: 173. doi:10.1007/s00232-005-0792-1
P-glycoprotein (P-gp) is an ATP-dependent drug pump that can transport a broad range of hydrophobic compounds out of the cell. The protein is clinically important because of its contribution to the phenomenon of multidrug resistance during AIDS/HIV and cancer chemotherapy. P-gp is a member of the ATP-binding cassette (ABC) family of proteins. It is a single polypeptide that contains two repeats joined by a linker region. Each repeat has a transmembrane domain consisting of six transmembrane segments followed by a hydrophilic domain containing the nucleotide-binding domain. In this mini-review, we discuss recent progress in determining the structure and mechanism of human P-glycoprotein.
KeywordsP-glycoproteinABC transporterSubstrate binding pocketATPase activityThiol cross-linkingInduced-fit mechanism
amino-terminal nucleotide binding domain;
carboxy-terminal nucleotide binding domain;