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

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dc.contributor.author Jones, Peter en_US
dc.contributor.author George, Anthony en_US
dc.contributor.editor en_US
dc.date.accessioned 2012-10-12T03:33:03Z
dc.date.available 2012-10-12T03:33:03Z
dc.date.issued 2012 en_US
dc.identifier 2011001406 en_US
dc.identifier.citation Jones Peter and George Anthony 2012, 'Role of the D-loops in allosteric control of ATP hydrolysis in an ABC transporter', American Chemical Society, vol. 116, no. 11, pp. 3004-3013. en_US
dc.identifier.issn 1089-5639 en_US
dc.identifier.other C1 en_US
dc.identifier.uri http://hdl.handle.net/10453/18025
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 gamma-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. en_US
dc.language en_US
dc.publisher American Chemical Society en_US
dc.relation.isbasedon http://dx.doi.org/10.1021/jp211139s en_US
dc.title Role of the D-loops in allosteric control of ATP hydrolysis in an ABC transporter en_US
dc.parent Journal of Physical Chemistry A en_US
dc.journal.volume 116 en_US
dc.journal.number 11 en_US
dc.publocation Washington DC, USA en_US
dc.identifier.startpage 3004 en_US
dc.identifier.endpage 3013 en_US
dc.cauo.name SCI.Medical and Molecular Biosciences en_US
dc.conference Verified OK en_US
dc.for 030600 en_US
dc.personcode 020174 en_US
dc.personcode 860231 en_US
dc.percentage 50 en_US
dc.classification.name Physical Chemistry (incl. Structural en_US
dc.classification.type FOR-08 en_US
dc.edition en_US
dc.custom en_US
dc.date.activity en_US
dc.location.activity en_US
dc.description.keywords BINDING CASSETTE TRANSPORTER; GLYCOPROTEIN MULTIDRUG TRANSPORTER; ASYMMETRIC OCCLUDED STATE; NUCLEOTIDE-BINDING; P-GLYCOPROTEIN; MOLECULAR-DYNAMICS; CATALYTIC CYCLE; ACTIVE-SITE; GLUTAMATE RESIDUES; CRYSTAL-STRUCTURE en_US
dc.staffid en_US
dc.staffid 860231 en_US


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