Multidrug efflux pumps: drug binding - gates or cavity?

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dc.contributor.authorCrowley, Emily
dc.contributor.authorCallaghan, Richard
dc.date.accessioned2015-12-07T22:44:52Z
dc.date.issued2010
dc.date.updated2016-02-24T10:26:21Z
dc.description.abstractThe role of the ATP-binding cassette ABCB1 in mediating the resistance to chemotherapy in many forms of cancer has been well established. The protein is also endogenously expressed in numerous barrier and excretory tissues, thereby regulating or impacting on drug pharmacokinetic profiles. Given these prominent roles in health and disease, a great deal of biochemical, structural and pharmacological research has been directed towards modulating its activity. Despite the effort, only a small handful of compounds have reached the later stages of clinical trials. What is responsible for this poor return on the heavy research investment? Perhaps the most significant factor is the lack of information on the location, physical features and chemical properties of the drug-binding site(s) in ABCB1. This minireview outlines the various strategies and outcomes of research efforts to pin-point the sites of interaction. The data may be assimilated into two working hypotheses to describe drug binding to ABCB1; (a) the central cavity and the (b) domain interface models.
dc.identifier.issn1742-464X
dc.identifier.urihttp://hdl.handle.net/1885/25383
dc.publisherBlackwell Publishing Ltd
dc.sourceThe FEBS Journal
dc.subjectKeywords: ABC transporter; adenosine triphosphatase; azidopine; glycoprotein P; multidrug efflux pump; multidrug resistance protein 1; tritium; unclassified drug; cancer resistance; drug binding; drug binding site; electron microscopy; human; matrix assisted laser Central cavity; Coupling; Domain interface; Drug binding; Drug resistance; Drug transport; Interdomain communication; Membrane protein; Multidrug binding; P-glycoprotein
dc.titleMultidrug efflux pumps: drug binding - gates or cavity?
dc.typeJournal article
local.bibliographicCitation.issue3
local.bibliographicCitation.lastpage539
local.bibliographicCitation.startpage530
local.contributor.affiliationCrowley, Emily, University of Oxford
local.contributor.affiliationCallaghan, Richard, College of Medicine, Biology and Environment, ANU
local.contributor.authoremailu5103268@anu.edu.au
local.contributor.authoruidCallaghan, Richard, u5103268
local.description.embargo2037-12-31
local.description.notesImported from ARIES
local.identifier.absfor060199 - Biochemistry and Cell Biology not elsewhere classified
local.identifier.absfor060112 - Structural Biology (incl. Macromolecular Modelling)
local.identifier.absfor060110 - Receptors and Membrane Biology
local.identifier.absseo970106 - Expanding Knowledge in the Biological Sciences
local.identifier.ariespublicationu4008405xPUB38
local.identifier.citationvolume277
local.identifier.doi10.1111/j.1742-4658.2009.07484.x
local.identifier.scopusID2-s2.0-75149147634
local.identifier.uidSubmittedByu4008405
local.type.statusPublished Version

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