Rate of hydrolysis in ATP synthase is fine-tuned by -subunit motif controlling active site conformation
Online Publication Date2013-01-23
Print Publication Date2013-02-05
Permanent link to this recordhttp://hdl.handle.net/10754/599446
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AbstractComputer-designed artificial enzymes will require precise understanding of how conformation of active sites may control barrier heights of key transition states, including dependence on structure and dynamics at larger molecular scale. F(o)F(1) ATP synthase is interesting as a model system: a delicate molecular machine synthesizing or hydrolyzing ATP using a rotary motor. Isolated F(1) performs hydrolysis with a rate very sensitive to ATP concentration. Experimental and theoretical results show that, at low ATP concentrations, ATP is slowly hydrolyzed in the so-called tight binding site, whereas at higher concentrations, the binding of additional ATP molecules induces rotation of the central γ-subunit, thereby forcing the site to transform through subtle conformational changes into a loose binding site in which hydrolysis occurs faster. How the 1-Å-scale rearrangements are controlled is not yet fully understood. By a combination of theoretical approaches, we address how large macromolecular rearrangements may manipulate the active site and how the reaction rate changes with active site conformation. Simulations reveal that, in response to γ-subunit position, the active site conformation is fine-tuned mainly by small α-subunit changes. Quantum mechanics-based results confirm that the sub-Ångström gradual changes between tight and loose binding site structures dramatically alter the hydrolysis rate.
CitationBeke-Somfai T, Lincoln P, Norden B (2013) Rate of hydrolysis in ATP synthase is fine-tuned by -subunit motif controlling active site conformation. Proceedings of the National Academy of Sciences 110: 2117–2122. Available: http://dx.doi.org/10.1073/pnas.1214741110.
SponsorsThis work is funded by King Abdullah University of Science and Technology and the European Research Council.
PubMed Central IDPMC3568300
CollectionsPublications Acknowledging KAUST Support
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