Fadda, Elisa and Yu, hing-Hsing and Pomès, Régis (2008) Electrostatic control of proton pumping in cytochrome c oxidase. Biochimica et Biophysica Acta (BBA) - Bioenergetics, 1777 (3). pp. 277-284. ISSN 0005-2728

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Abstract

As part of the mitochondrial respiratory chain, cytochrome c oxidase utilizes the energy produced by the reduction of O2 to water to fuel vectorial proton transport. The mechanism coupling proton pumping to redox chemistry is unknown. Recent advances have provided evidence that each of the four observable transitions in the complex catalytic cycle consists of a similar sequence of events. However, the physico-chemical basis underlying this recurring sequence has not been identified. We identify this recurring pattern based on a comprehensive model of the catalytic cycle derived from the analysis of oxygen chemistry and available experimental evidence. The catalytic cycle involves the periodic repetition of a sequence of three states differing in the spatial distribution of charge in the active site: [0|1], [1|0], and [1|1], where the total charge of heme a and the binuclear center appears on the left and on the right, respectively. This sequence recurs four times per turnover despite differences in the redox chemistry. This model leads to a simple, robust, and reproducible sequence of electron and proton transfer steps and rationalizes the pumping mechanism in terms of electrostatic coupling of proton translocation to redox chemistry. Continuum electrostatic calculations support the proposed mechanism and suggest an electrostatic origin for the decoupled and inactive phenotypes of ionic mutants in the principal proton-uptake pathway.

Item Type:	Article
Keywords:	Cytochrome c oxidase; Vectorial proton transport; Redox-coupled proton transport; Proton-pumping mechanism; Binuclear center; Continuum electrostatics;
Academic Unit:	Faculty of Science and Engineering > Chemistry
Item ID:	7827
Identification Number:	https://doi.org/10.1016/j.bbabio.2007.11.010
Depositing User:	Elisa Fadda
Date Deposited:	30 Jan 2017 15:09
Journal or Publication Title:	Biochimica et Biophysica Acta (BBA) - Bioenergetics
Publisher:	Elsevier
Refereed:	Yes
URI:	http://www.sciencedirect.com
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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