Journal
JOURNAL OF CHEMICAL INFORMATION AND MODELING
Volume 53, Issue 7, Pages 1747-1760Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ci400195v
Keywords
-
Categories
Funding
- Fundacao para a Ciencia e Tecnologia, I.P. (FCT, Portugal) [PTDC/QUI-QUI/099815/2008, Pest-OE/SAU/UI4013/2011, PTDC/QEQ-MED/0905/2012]
- FCT [SFRH/BD/84285/2012]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/84285/2012, PTDC/QUI-QUI/099815/2008, PEst-OE/SAU/UI4013/2011, PTDC/QEQ-MED/0905/2012] Funding Source: FCT
Ask authors/readers for more resources
P-Glycoprotein (Pgp) is one of the best characterized ABC transporters, often involved in the multidrug-resistance phenotype overexpressed by several cancer cell lines. Experimental studies contributed to important knowledge concerning substrate polyspecificity, efflux mechanism, and drug-binding sites. This information is, however, scattered through different perspectives, not existing a unifying model for the knowledge available for this transporter. Using a previously refined structure of murine Pgp, three putative drug-binding sites were hereby characterized by means of molecular docking. The modulator site (M-site) is characterized by cross interactions between both Pgp halves herein defined for the first time, having an important role in impairing conformational changes leading to substrate efflux. Two other binding sites, located next to the inner leaflet of the lipid bilayer, were identified as the substrate-binding H and R sites by matching docking and experimental results. A new classification model with the ability to discriminate substrates from modulators is also proposed, integrating a vast number of theoretical and experimental data.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available