Mechanism of ABC transporters: A molecular dynamics simulation of a well characterized nucleotide-binding subunit

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dc.contributor.author Jones, PM
dc.contributor.author George, AM
dc.date.accessioned 2009-06-26T04:22:42Z
dc.date.issued 2002-10-01
dc.identifier.citation Proceedings of the National Academy of Sciences of the United States of America, 2002, 99 (20), pp. 12639 - 12644
dc.identifier.issn 0027-8424
dc.identifier.other C1 en_US
dc.identifier.uri http://hdl.handle.net/10453/811
dc.description.abstract ATP-binding cassette (ABC) transporters are membrane-bound molecular pumps that form one of the largest of all protein families. Several of them are central to phenomena of biomedical interest, including cystic fibrosis and resistance to chemotherapeutic drugs. ABC transporters share a common architecture comprising two hydrophilic nucleotide-binding domains (NBDs) and two hydrophobic transmembrane domains (TMDs) that form the substrate pathway across the membrane. The conformational changes in the NBDs induced by ATP hydrolysis and the means by which they are transmitted to the TMDs to effect substrate translocation remain largely unknown. We have performed a molecular dynamics simulation of HisP, the well studied NBD of the bacterial histidine permease, to identify hinges and switches of the NBD conformational transitions and subunit-subunit interfaces. This analysis reveals that the TMDs regulate ATP hydrolysis by controlling conformational transitions of the NBD helical domains, and identifies the conformational changes and the crucial TMD:NBD interface, by which the energy of ATP hydrolysis is transmitted to the TMDs. We also define the conformational transitions of the Q-loop, a key element of the NBD mechanism, and identify pathways by which Q-loop switching is coordinated with TMD and NBD conformational changes. We propose a model for the catalytic cycle of ABC transporters that shows how substrate-binding and transport by the TMDs may be coordinated and coupled with ATP binding and hydrolysis in the NBDs.
dc.language eng
dc.relation.isbasedon 10.1073/pnas.152439599
dc.title Mechanism of ABC transporters: A molecular dynamics simulation of a well characterized nucleotide-binding subunit
dc.type Journal Article
dc.parent Proceedings of the National Academy of Sciences of the United States of America
dc.journal.volume 20
dc.journal.volume 99
dc.journal.number 20 en_US
dc.publocation USA en_US
dc.identifier.startpage 12639 en_US
dc.identifier.endpage 12644 en_US
dc.cauo.name SCI.Faculty of Science en_US
dc.conference Verified OK en_US
dc.for 060107 Enzymes
dc.for 110106 Medical Biochemistry: Proteins and Peptides (Incl. Medical Proteomics)
dc.personcode 020174
dc.personcode 860231
dc.percentage 50 en_US
dc.classification.name Medical Biochemistry: Proteins and Peptides (incl. Medical Proteomics) en_US
dc.classification.type FOR-08 en_US
pubs.embargo.period Not known
pubs.organisational-group /University of Technology Sydney
pubs.organisational-group /University of Technology Sydney/Faculty of Science
pubs.organisational-group /University of Technology Sydney/Faculty of Science/School of Medical and Molecular Sciences
pubs.organisational-group /University of Technology Sydney/Strength - i3
utslib.copyright.status Closed Access
utslib.copyright.date 2015-04-15 12:17:09.805752+10
pubs.consider-herdc true


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