Role of the D-loops in allosteric control of ATP hydrolysis in an ABC transporter

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Show simple item record Jones, PM George, AM 2012-10-12T03:33:03Z 2012-03-22
dc.identifier.citation Journal of Physical Chemistry A, 2012, 116 (11), pp. 3004 - 3013
dc.identifier.issn 1089-5639
dc.identifier.other C1 en_US
dc.description.abstract ABC transporters couple ATP hydrolysis to movement of substrates across cell membranes. They comprise two transmembrane domains and two cytosolic nucleotide-binding domains forming two active sites that hydrolyze ATP cooperatively. The mechanism of ATP hydrolysis is controversial and the structural dynamic basis of its allosteric control unknown. Here we report molecular dynamics simulations of the ATP/apo and ATP/ADP states of the bacterial ABC exporter Sav1866, in which the cytoplasmic region of the protein was simulated in explicit water for 150 ns. In the simulation of the ATP/apo state, we observed, for the first time, conformers of the active site with the canonical geometry for an in-line nucleophilic attack on the ATP γ-phosphate. The conserved glutamate immediately downstream of the Walker B motif is the catalytic base, forming a dyad with the H-loop histidine, whereas the Q-loop glutamine has an organizing role. Each D-loop provides a coordinating residue of the attacking water, and comparison with the simulation of the ATP/ADP state suggests that via their flexibility, the D-loops modulate formation of the hydrolysis-competent state. A global switch involving a coupling helix delineates the signal transmission route by which allosteric control of ATP hydrolysis in ABC transporters is mediated. © 2012 American Chemical Society.
dc.language eng
dc.relation.isbasedon 10.1021/jp211139s
dc.title Role of the D-loops in allosteric control of ATP hydrolysis in an ABC transporter
dc.type Journal Article
dc.parent Journal of Physical Chemistry A
dc.journal.volume 11
dc.journal.volume 116
dc.journal.number 11 en_US
dc.publocation Washington DC, USA en_US
dc.publocation Proceedings of 18th Annual Pacific-Rim Real Estate Society Conference
dc.identifier.startpage 3004 en_US
dc.identifier.endpage 3013 en_US SCI.Medical and Molecular Biosciences en_US
dc.conference Verified OK en_US
dc.conference Annual Pacific-Rim Real Estate Society Conference
dc.for 0306 Physical Chemistry (Incl. Structural)
dc.personcode 020174
dc.personcode 860231
dc.percentage 100 en_US Physical Chemistry (incl. Structural en_US
dc.classification.type FOR-08 en_US
dc.edition en_US
dc.custom en_US en_US 2012-01-15
dc.location.activity en_US
dc.location.activity Adelaide, Australia
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/Strength - i3
utslib.copyright.status Closed Access 2015-04-15 12:17:09.805752+10
pubs.consider-herdc true
utslib.collection.history School of Medical and Molecular Sciences (ID: 341)
utslib.collection.history Closed (ID: 3)

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