Double-lock ratchet mechanism revealing the role of  SER-344 in FoF1 ATP synthase

Handle URI:
http://hdl.handle.net/10754/598016
Title:
Double-lock ratchet mechanism revealing the role of  SER-344 in FoF1 ATP synthase
Authors:
Beke-Somfai, T.; Lincoln, P.; Norden, B.
Abstract:
In a majority of living organisms, FoF1 ATP synthase performs the fundamental process of ATP synthesis. Despite the simple net reaction formula, ADP+Pi→ATP+H2O, the detailed step-by-step mechanism of the reaction yet remains to be resolved owing to the complexity of this multisubunit enzyme. Based on quantum mechanical computations using recent high resolution X-ray structures, we propose that during ATP synthesis the enzyme first prepares the inorganic phosphate for the γP-OADP bond-forming step via a double-proton transfer. At this step, the highly conserved αS344 side chain plays a catalytic role. The reaction thereafter progresses through another transition state (TS) having a planar ion configuration to finally form ATP. These two TSs are concluded crucial for ATP synthesis. Using stepwise scans and several models of the nucleotide-bound active site, some of the most important conformational changes were traced toward direction of synthesis. Interestingly, as the active site geometry progresses toward the ATP-favoring tight binding site, at both of these TSs, a dramatic increase in barrier heights is observed for the reverse direction, i.e., hydrolysis of ATP. This change could indicate a "ratchet" mechanism for the enzyme to ensure efficacy of ATP synthesis by shifting residue conformation and thus locking access to the crucial TSs.
Citation:
Beke-Somfai T, Lincoln P, Norden B (2011) Double-lock ratchet mechanism revealing the role of  SER-344 in FoF1 ATP synthase. Proceedings of the National Academy of Sciences 108: 4828–4833. Available: http://dx.doi.org/10.1073/pnas.1010453108.
Publisher:
Proceedings of the National Academy of Sciences
Journal:
Proceedings of the National Academy of Sciences
KAUST Grant Number:
KUK-11-008-23
Issue Date:
7-Mar-2011
DOI:
10.1073/pnas.1010453108
PubMed ID:
21383131
PubMed Central ID:
PMC3064393
Type:
Article
ISSN:
0027-8424; 1091-6490
Sponsors:
This work is funded by King Abdullah University of Science and Technology (Grant KUK-11-008-23). The Eötvös University computer facility, the High Performance Computing Group (University of Szeged), and the Swedish National Infrastructure for Computing resources were used for calculations.
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Full metadata record

DC FieldValue Language
dc.contributor.authorBeke-Somfai, T.en
dc.contributor.authorLincoln, P.en
dc.contributor.authorNorden, B.en
dc.date.accessioned2016-02-25T13:11:02Zen
dc.date.available2016-02-25T13:11:02Zen
dc.date.issued2011-03-07en
dc.identifier.citationBeke-Somfai T, Lincoln P, Norden B (2011) Double-lock ratchet mechanism revealing the role of  SER-344 in FoF1 ATP synthase. Proceedings of the National Academy of Sciences 108: 4828–4833. Available: http://dx.doi.org/10.1073/pnas.1010453108.en
dc.identifier.issn0027-8424en
dc.identifier.issn1091-6490en
dc.identifier.pmid21383131en
dc.identifier.doi10.1073/pnas.1010453108en
dc.identifier.urihttp://hdl.handle.net/10754/598016en
dc.description.abstractIn a majority of living organisms, FoF1 ATP synthase performs the fundamental process of ATP synthesis. Despite the simple net reaction formula, ADP+Pi→ATP+H2O, the detailed step-by-step mechanism of the reaction yet remains to be resolved owing to the complexity of this multisubunit enzyme. Based on quantum mechanical computations using recent high resolution X-ray structures, we propose that during ATP synthesis the enzyme first prepares the inorganic phosphate for the γP-OADP bond-forming step via a double-proton transfer. At this step, the highly conserved αS344 side chain plays a catalytic role. The reaction thereafter progresses through another transition state (TS) having a planar ion configuration to finally form ATP. These two TSs are concluded crucial for ATP synthesis. Using stepwise scans and several models of the nucleotide-bound active site, some of the most important conformational changes were traced toward direction of synthesis. Interestingly, as the active site geometry progresses toward the ATP-favoring tight binding site, at both of these TSs, a dramatic increase in barrier heights is observed for the reverse direction, i.e., hydrolysis of ATP. This change could indicate a "ratchet" mechanism for the enzyme to ensure efficacy of ATP synthesis by shifting residue conformation and thus locking access to the crucial TSs.en
dc.description.sponsorshipThis work is funded by King Abdullah University of Science and Technology (Grant KUK-11-008-23). The Eötvös University computer facility, the High Performance Computing Group (University of Szeged), and the Swedish National Infrastructure for Computing resources were used for calculations.en
dc.publisherProceedings of the National Academy of Sciencesen
dc.subjectMolecular motoren
dc.subjectQuantum mechanicsen
dc.subjectReaction mechanismen
dc.subject.meshModels, Molecularen
dc.titleDouble-lock ratchet mechanism revealing the role of  SER-344 in FoF1 ATP synthaseen
dc.typeArticleen
dc.identifier.journalProceedings of the National Academy of Sciencesen
dc.identifier.pmcidPMC3064393en
dc.contributor.institutionChalmers University of Technology, Göteborg, Swedenen
dc.contributor.institutionEötvös Loránd University, Budapest, Hungaryen
kaust.grant.numberKUK-11-008-23en
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