Rate of hydrolysis in ATP synthase is fine-tuned by  -subunit motif controlling active site conformation

Handle URI:
http://hdl.handle.net/10754/599446
Title:
Rate of hydrolysis in ATP synthase is fine-tuned by  -subunit motif controlling active site conformation
Authors:
Beke-Somfai, T.; Lincoln, P.; Norden, B.
Abstract:
Computer-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.
Citation:
Beke-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.
Publisher:
Proceedings of the National Academy of Sciences
Journal:
Proceedings of the National Academy of Sciences
Issue Date:
23-Jan-2013
DOI:
10.1073/pnas.1214741110
PubMed ID:
23345443
PubMed Central ID:
PMC3568300
Type:
Article
ISSN:
0027-8424; 1091-6490
Sponsors:
This work is funded by King Abdullah University of Science and Technology and the European Research Council.
Appears in Collections:
Publications Acknowledging KAUST Support

Full metadata record

DC FieldValue Language
dc.contributor.authorBeke-Somfai, T.en
dc.contributor.authorLincoln, P.en
dc.contributor.authorNorden, B.en
dc.date.accessioned2016-02-28T05:51:17Zen
dc.date.available2016-02-28T05:51:17Zen
dc.date.issued2013-01-23en
dc.identifier.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.en
dc.identifier.issn0027-8424en
dc.identifier.issn1091-6490en
dc.identifier.pmid23345443en
dc.identifier.doi10.1073/pnas.1214741110en
dc.identifier.urihttp://hdl.handle.net/10754/599446en
dc.description.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.en
dc.description.sponsorshipThis work is funded by King Abdullah University of Science and Technology and the European Research Council.en
dc.publisherProceedings of the National Academy of Sciencesen
dc.subjectEnzyme catalysisen
dc.subjectMolecular dynamicsen
dc.subjectProtein structureen
dc.titleRate of hydrolysis in ATP synthase is fine-tuned by  -subunit motif controlling active site conformationen
dc.typeArticleen
dc.identifier.journalProceedings of the National Academy of Sciencesen
dc.identifier.pmcidPMC3568300en
dc.contributor.institutionChalmers University of Technology, Göteborg, Swedenen
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