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The Journal of Membrane Biology

, Volume 206, Issue 3, pp 173–185 | Cite as

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

  • T.W. Loo
  • D.M. Clarke
Topical Review

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-glycoprotein ABC transporter Substrate binding pocket ATPase activity Thiol cross-linking Induced-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

Notes

Acknowledgment

This work was supported by grants from the National Cancer Institute of Canada through the Canadian Cancer Society and from the Canadian Institutes of Health Research. DMC is the recipient of the Canada Research Chair in Membrane Biology.

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© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

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

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