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The Role of the Lipid Bilayer in P-glycoprotein Drug Binding, Transport and Catalytic Functions

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dc.contributor.advisor Frances, Sharom
dc.contributor.author Clay, Adam Thomas
dc.date.accessioned 2011-12-16T15:24:41Z
dc.date.available 2011-12-16T15:24:41Z
dc.date.copyright 2011-12
dc.date.created 2011-12-08
dc.date.issued 2011-12-16
dc.identifier.uri http://hdl.handle.net/10214/3196
dc.description.abstract The ABC protein P-glycoprotein (Pgp, ABCB1) transports many structurally diverse substrates from the lipid bilayer. Previous studies demonstrated the importance of the membrane environment, but few have quantified these effects. In the present work, purified Pgp reconstituted into defined lipid systems was employed. Drug binding affinities were determined using Trp quenching, and drug-lipid partitioning by equilibrium dialysis. Pgp bound substrates from the bilayer with affinities in the millimolar range; both drug-Pgp and drug-lipid interactions were important. The kinetics of Pgp-mediated drug transport were sensitive to drug structure and lipid environment. The rate of transport is proposed to depend on the affinity of Pgp for substrate and conformational changes. The lipid bilayer affected the stability of Pgp catalytic activity which provided evidence for distinct basal and drug-stimulated ATPase cycles. Overall, the lipid environment had pronounced effects on Pgp-mediated drug binding, transport and catalytic functions. en_US
dc.description.sponsorship Canadian Cancer Society en_US
dc.language.iso en en_US
dc.subject P-glycoprotein en_US
dc.subject Pgp en_US
dc.subject ABCB1 en_US
dc.subject drug binding en_US
dc.subject drug transport en_US
dc.title The Role of the Lipid Bilayer in P-glycoprotein Drug Binding, Transport and Catalytic Functions en_US
dc.type Thesis en_US
dc.degree.programme Biophysics en_US
dc.degree.name Master of Science en_US
dc.degree.department Department of Molecular and Cellular Biology en_US
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