The Journal of Membrane Biology

, Volume 206, Issue 3, pp 173–185

Recent Progress in Understanding the Mechanism of P-Glycoprotein-mediated Drug Efflux

Topical Review

DOI: 10.1007/s00232-005-0792-1

Cite this article as:
Loo, T. & Clarke, D. J Membrane Biol (2005) 206: 173. doi:10.1007/s00232-005-0792-1

Abstract

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.

Keywords

P-glycoproteinABC transporterSubstrate binding pocketATPase activityThiol cross-linkingInduced-fit mechanism

Abbreviations

M6M,

1,6-hexanediyl bismethanethiosulfonate;

M8M,

3,6-dioxaoctane-1,8-diyl bismethanethiosulfonate;

NBD1,

amino-terminal nucleotide binding domain;

NBD2,

carboxy-terminal nucleotide binding domain;

P-gp,

P-glycoprotein;

TMD,

transmembrane domain;

TM,

transmembrane

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  1. 1.Department of Medicine and Department of BiochemistryUniversity of TorontoTorontoCanada