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Atomistic determinants of co-enzyme Q reduction at the Q(i)-site of the cytochrome bc(1) complex

The cytochrome (cyt) bc(1) complex is an integral component of the respiratory electron transfer chain sustaining the energy needs of organisms ranging from humans to bacteria. Due to its ubiquitous role in the energy metabolism, both the oxidation and reduction of the enzyme’s substrate co-enzyme Q...

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Autores principales: Postila, Pekka A., Kaszuba, Karol, Kuleta, Patryk, Vattulainen, Ilpo, Sarewicz, Marcin, Osyczka, Artur, Róg, Tomasz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5035994/
https://www.ncbi.nlm.nih.gov/pubmed/27667198
http://dx.doi.org/10.1038/srep33607
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author Postila, Pekka A.
Kaszuba, Karol
Kuleta, Patryk
Vattulainen, Ilpo
Sarewicz, Marcin
Osyczka, Artur
Róg, Tomasz
author_facet Postila, Pekka A.
Kaszuba, Karol
Kuleta, Patryk
Vattulainen, Ilpo
Sarewicz, Marcin
Osyczka, Artur
Róg, Tomasz
author_sort Postila, Pekka A.
collection PubMed
description The cytochrome (cyt) bc(1) complex is an integral component of the respiratory electron transfer chain sustaining the energy needs of organisms ranging from humans to bacteria. Due to its ubiquitous role in the energy metabolism, both the oxidation and reduction of the enzyme’s substrate co-enzyme Q has been studied vigorously. Here, this vast amount of data is reassessed after probing the substrate reduction steps at the Q(i)-site of the cyt bc(1) complex of Rhodobacter capsulatus using atomistic molecular dynamics simulations. The simulations suggest that the Lys251 side chain could rotate into the Q(i)-site to facilitate binding of half-protonated semiquinone – a reaction intermediate that is potentially formed during substrate reduction. At this bent pose, the Lys251 forms a salt bridge with the Asp252, thus making direct proton transfer possible. In the neutral state, the lysine side chain stays close to the conserved binding location of cardiolipin (CL). This back-and-forth motion between the CL and Asp252 indicates that Lys251 functions as a proton shuttle controlled by pH-dependent negative feedback. The CL/K/D switching, which represents a refinement to the previously described CL/K pathway, fine-tunes the proton transfer process. Lastly, the simulation data was used to formulate a mechanism for reducing the substrate at the Q(i)-site.
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spelling pubmed-50359942016-09-30 Atomistic determinants of co-enzyme Q reduction at the Q(i)-site of the cytochrome bc(1) complex Postila, Pekka A. Kaszuba, Karol Kuleta, Patryk Vattulainen, Ilpo Sarewicz, Marcin Osyczka, Artur Róg, Tomasz Sci Rep Article The cytochrome (cyt) bc(1) complex is an integral component of the respiratory electron transfer chain sustaining the energy needs of organisms ranging from humans to bacteria. Due to its ubiquitous role in the energy metabolism, both the oxidation and reduction of the enzyme’s substrate co-enzyme Q has been studied vigorously. Here, this vast amount of data is reassessed after probing the substrate reduction steps at the Q(i)-site of the cyt bc(1) complex of Rhodobacter capsulatus using atomistic molecular dynamics simulations. The simulations suggest that the Lys251 side chain could rotate into the Q(i)-site to facilitate binding of half-protonated semiquinone – a reaction intermediate that is potentially formed during substrate reduction. At this bent pose, the Lys251 forms a salt bridge with the Asp252, thus making direct proton transfer possible. In the neutral state, the lysine side chain stays close to the conserved binding location of cardiolipin (CL). This back-and-forth motion between the CL and Asp252 indicates that Lys251 functions as a proton shuttle controlled by pH-dependent negative feedback. The CL/K/D switching, which represents a refinement to the previously described CL/K pathway, fine-tunes the proton transfer process. Lastly, the simulation data was used to formulate a mechanism for reducing the substrate at the Q(i)-site. Nature Publishing Group 2016-09-26 /pmc/articles/PMC5035994/ /pubmed/27667198 http://dx.doi.org/10.1038/srep33607 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Postila, Pekka A.
Kaszuba, Karol
Kuleta, Patryk
Vattulainen, Ilpo
Sarewicz, Marcin
Osyczka, Artur
Róg, Tomasz
Atomistic determinants of co-enzyme Q reduction at the Q(i)-site of the cytochrome bc(1) complex
title Atomistic determinants of co-enzyme Q reduction at the Q(i)-site of the cytochrome bc(1) complex
title_full Atomistic determinants of co-enzyme Q reduction at the Q(i)-site of the cytochrome bc(1) complex
title_fullStr Atomistic determinants of co-enzyme Q reduction at the Q(i)-site of the cytochrome bc(1) complex
title_full_unstemmed Atomistic determinants of co-enzyme Q reduction at the Q(i)-site of the cytochrome bc(1) complex
title_short Atomistic determinants of co-enzyme Q reduction at the Q(i)-site of the cytochrome bc(1) complex
title_sort atomistic determinants of co-enzyme q reduction at the q(i)-site of the cytochrome bc(1) complex
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5035994/
https://www.ncbi.nlm.nih.gov/pubmed/27667198
http://dx.doi.org/10.1038/srep33607
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