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

Tamas Beke-Somfai (Institutionen för kemi- och bioteknik, Fysikalisk kemi) ; Per Lincoln (Institutionen för kemi- och bioteknik, Fysikalisk kemi) ; Bengt Nordén (Institutionen för kemi- och bioteknik, Fysikalisk kemi)
Proceedings of the National Academy of Sciences of the United States of America (0027-8424). Vol. 110 (2013), 6, p. 2117-2122.
[Artikel, refereegranskad vetenskaplig]

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. FoF1 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 gamma-subunit, thereby forcing the site to transform through subtle conformational changes into a loose binding site in which hydrolysis occurs faster. How the 1-angstrom-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.-subunit position, the active site conformation is fine-tuned mainly by small alpha-subunit changes. Quantum mechanics-based results confirm that the sub-Angstrom gradual changes between tight and loose binding site structures dramatically alter the hydrolysis rate.

Denna post skapades 2013-03-21.
CPL Pubid: 174889


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Institutioner (Chalmers)

Institutionen för kemi- och bioteknik, Fysikalisk kemi (2005-2014)



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