Double-lock ratchet mechanism revealing the role of SER-344 in FoF1 ATP synthase
KAUST Grant NumberKUK-11-008-23
Online Publication Date2011-03-07
Print Publication Date2011-03-22
Permanent link to this recordhttp://hdl.handle.net/10754/598016
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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.
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.
SponsorsThis 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.
PubMed Central IDPMC3064393
CollectionsPublications Acknowledging KAUST Support
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