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The Redox-Active Tyrosine Is Essential for Proton Pumping in Cytochrome c Oxidase

Cellular respiration involves electron transport via a number of enzyme complexes to the terminal Cytochrome c oxidase (CcO), in which molecular oxygen is reduced to water. The free energy released in the reduction process is used to establish a transmembrane electrochemical gradient, via two proces...

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Autor principal: Blomberg, Margareta R. A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079940/
https://www.ncbi.nlm.nih.gov/pubmed/33937193
http://dx.doi.org/10.3389/fchem.2021.640155
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author Blomberg, Margareta R. A.
author_facet Blomberg, Margareta R. A.
author_sort Blomberg, Margareta R. A.
collection PubMed
description Cellular respiration involves electron transport via a number of enzyme complexes to the terminal Cytochrome c oxidase (CcO), in which molecular oxygen is reduced to water. The free energy released in the reduction process is used to establish a transmembrane electrochemical gradient, via two processes, both corresponding to charge transport across the membrane in which the enzymes are embedded. First, the reduction chemistry occurring in the active site of CcO is electrogenic, which means that the electrons and protons are delivered from opposite sides of the membrane. Second, the exergonic chemistry is coupled to translocation of protons across the entire membrane, referred to as proton pumping. In the largest subfamily of the CcO enzymes, the A-family, one proton is pumped for every electron needed for the chemistry, making the energy conservation particularly efficient. In the present study, hybrid density functional calculations are performed on a model of the A-family CcOs. The calculations show that the redox-active tyrosine, conserved in all types of CcOs, plays an essential role for the energy conservation. Based on the calculations a reaction mechanism is suggested involving a tyrosyl radical (possibly mixed with tyrosinate character) in all reduction steps. The result is that the free energy released in each reduction step is large enough to allow proton pumping in all reduction steps without prohibitively high barriers when the gradient is present. Furthermore, the unprotonated tyrosine provides a mechanism for coupling the uptake of two protons per electron in every reduction step, i.e. for a secure proton pumping.
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spelling pubmed-80799402021-04-29 The Redox-Active Tyrosine Is Essential for Proton Pumping in Cytochrome c Oxidase Blomberg, Margareta R. A. Front Chem Chemistry Cellular respiration involves electron transport via a number of enzyme complexes to the terminal Cytochrome c oxidase (CcO), in which molecular oxygen is reduced to water. The free energy released in the reduction process is used to establish a transmembrane electrochemical gradient, via two processes, both corresponding to charge transport across the membrane in which the enzymes are embedded. First, the reduction chemistry occurring in the active site of CcO is electrogenic, which means that the electrons and protons are delivered from opposite sides of the membrane. Second, the exergonic chemistry is coupled to translocation of protons across the entire membrane, referred to as proton pumping. In the largest subfamily of the CcO enzymes, the A-family, one proton is pumped for every electron needed for the chemistry, making the energy conservation particularly efficient. In the present study, hybrid density functional calculations are performed on a model of the A-family CcOs. The calculations show that the redox-active tyrosine, conserved in all types of CcOs, plays an essential role for the energy conservation. Based on the calculations a reaction mechanism is suggested involving a tyrosyl radical (possibly mixed with tyrosinate character) in all reduction steps. The result is that the free energy released in each reduction step is large enough to allow proton pumping in all reduction steps without prohibitively high barriers when the gradient is present. Furthermore, the unprotonated tyrosine provides a mechanism for coupling the uptake of two protons per electron in every reduction step, i.e. for a secure proton pumping. Frontiers Media S.A. 2021-04-14 /pmc/articles/PMC8079940/ /pubmed/33937193 http://dx.doi.org/10.3389/fchem.2021.640155 Text en Copyright © 2021 Blomberg. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Chemistry
Blomberg, Margareta R. A.
The Redox-Active Tyrosine Is Essential for Proton Pumping in Cytochrome c Oxidase
title The Redox-Active Tyrosine Is Essential for Proton Pumping in Cytochrome c Oxidase
title_full The Redox-Active Tyrosine Is Essential for Proton Pumping in Cytochrome c Oxidase
title_fullStr The Redox-Active Tyrosine Is Essential for Proton Pumping in Cytochrome c Oxidase
title_full_unstemmed The Redox-Active Tyrosine Is Essential for Proton Pumping in Cytochrome c Oxidase
title_short The Redox-Active Tyrosine Is Essential for Proton Pumping in Cytochrome c Oxidase
title_sort redox-active tyrosine is essential for proton pumping in cytochrome c oxidase
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079940/
https://www.ncbi.nlm.nih.gov/pubmed/33937193
http://dx.doi.org/10.3389/fchem.2021.640155
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