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Protonation of the binuclear active site in cytochrome c oxidase decreases the reduction potential of Cu-B
Stockholm University, Faculty of Science, Department of Organic Chemistry.
Stockholm University, Faculty of Science, Department of Organic Chemistry.
Number of Authors: 2
2015 (English)In: Biochimica et Biophysica Acta - Bioenergetics, ISSN 0005-2728, E-ISSN 1879-2650, Vol. 1847, no 10, 1173-1180 p.Article in journal (Refereed) Published
Abstract [en]

One of the remaining mysteries regarding the respiratory enzyme cytochrome c oxidase is how proton pumping can occur in all reduction steps in spite of the low reduction potentials observed in equilibrium titration experiments for two of the active site cofactors, CUB(II) and Fe-a3(III). It has been speculated that, at least the copper cofactor can acquire two different states, one metastable activated state occurring during enzyme turnover, and one relaxed state with lower energy, reached only when the supply of electrons stops. The activated state should have a transiently increased Cu-B(II) reduction potential, allowing proton pumping. The relaxed state should have a lower reduction potential, as measured in the titration experiments. However, the structures of these two states are not known. Quantum mechanical calculations show that the proton coupled reduction potential for Cu-B is inherently high in the active site as it appears after reaction with oxygen, which explains the observed proton pumping. It is suggested here that, when the flow of electrons ceases, a relaxed resting state is formed by the uptake of one extra proton, on top of the charge compensating protons delivered in each reduction step. The extra proton in the active site decreases the proton coupled reduction potential for Cu-B by almost half a volt, leading to agreement with titration experiments. Furthermore, the structure for the resting state with an extra proton is found to have a hydroxo-bridge between Cu-B(II) and Fe-a3(III), yielding a magnetic coupling that can explain the experimentally observed EPR silence.

Place, publisher, year, edition, pages
2015. Vol. 1847, no 10, 1173-1180 p.
Keyword [en]
Cytochrome c oxidase, Density functional theory, Reduction potentials, Magnetic coupling, Oxidized state
National Category
Biological Sciences Chemical Sciences
URN: urn:nbn:se:su:diva-121614DOI: 10.1016/j.bbabio.2015.06.008ISI: 000360872100016OAI: diva2:860278
Available from: 2015-10-12 Created: 2015-10-12 Last updated: 2015-10-12Bibliographically approved

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Blomberg, Margareta R. A.Siegbahn, Per E. M.
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