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Hydrogen bonding rearrangement by a mitochondrial disease mutation in cytochrome bc(1) perturbs heme b(H) redox potential and spin state

Hemes are common elements of biological redox cofactor chains involved in rapid electron transfer. While the redox properties of hemes and the stability of the spin state are recognized as key determinants of their function, understanding the molecular basis of control of these properties is challen...

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Autores principales: Kuleta, Patryk, Lasham, Jonathan, Sarewicz, Marcin, Ekiert, Iwona, Sharma, Vivek, Ekiert, Robert, Osyczka, Artur
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379992/
https://www.ncbi.nlm.nih.gov/pubmed/34389670
http://dx.doi.org/10.1073/pnas.2026169118
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author Kuleta, Patryk
Lasham, Jonathan
Sarewicz, Marcin
Ekiert, Iwona
Sharma, Vivek
Ekiert, Robert
Osyczka, Artur
author_facet Kuleta, Patryk
Lasham, Jonathan
Sarewicz, Marcin
Ekiert, Iwona
Sharma, Vivek
Ekiert, Robert
Osyczka, Artur
author_sort Kuleta, Patryk
collection PubMed
description Hemes are common elements of biological redox cofactor chains involved in rapid electron transfer. While the redox properties of hemes and the stability of the spin state are recognized as key determinants of their function, understanding the molecular basis of control of these properties is challenging. Here, benefiting from the effects of one mitochondrial disease–related point mutation in cytochrome b, we identify a dual role of hydrogen bonding (H-bond) to the propionate group of heme b(H) of cytochrome bc(1), a common component of energy-conserving systems. We found that replacing conserved glycine with serine in the vicinity of heme b(H) caused stabilization of this bond, which not only increased the redox potential of the heme but also induced structural and energetic changes in interactions between Fe ion and axial histidine ligands. The latter led to a reversible spin conversion of the oxidized Fe from 1/2 to 5/2, an effect that potentially reduces the electron transfer rate between the heme and its redox partners. We thus propose that H-bond to the propionate group and heme-protein packing contribute to the fine-tuning of the redox potential of heme and maintaining its proper spin state. A subtle balance is needed between these two contributions: While increasing the H-bond stability raises the heme potential, the extent of increase must be limited to maintain the low spin and diamagnetic form of heme. This principle might apply to other native heme proteins and can be exploited in engineering of artificial heme-containing protein maquettes.
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spelling pubmed-83799922021-08-30 Hydrogen bonding rearrangement by a mitochondrial disease mutation in cytochrome bc(1) perturbs heme b(H) redox potential and spin state Kuleta, Patryk Lasham, Jonathan Sarewicz, Marcin Ekiert, Iwona Sharma, Vivek Ekiert, Robert Osyczka, Artur Proc Natl Acad Sci U S A Biological Sciences Hemes are common elements of biological redox cofactor chains involved in rapid electron transfer. While the redox properties of hemes and the stability of the spin state are recognized as key determinants of their function, understanding the molecular basis of control of these properties is challenging. Here, benefiting from the effects of one mitochondrial disease–related point mutation in cytochrome b, we identify a dual role of hydrogen bonding (H-bond) to the propionate group of heme b(H) of cytochrome bc(1), a common component of energy-conserving systems. We found that replacing conserved glycine with serine in the vicinity of heme b(H) caused stabilization of this bond, which not only increased the redox potential of the heme but also induced structural and energetic changes in interactions between Fe ion and axial histidine ligands. The latter led to a reversible spin conversion of the oxidized Fe from 1/2 to 5/2, an effect that potentially reduces the electron transfer rate between the heme and its redox partners. We thus propose that H-bond to the propionate group and heme-protein packing contribute to the fine-tuning of the redox potential of heme and maintaining its proper spin state. A subtle balance is needed between these two contributions: While increasing the H-bond stability raises the heme potential, the extent of increase must be limited to maintain the low spin and diamagnetic form of heme. This principle might apply to other native heme proteins and can be exploited in engineering of artificial heme-containing protein maquettes. National Academy of Sciences 2021-08-17 2021-08-13 /pmc/articles/PMC8379992/ /pubmed/34389670 http://dx.doi.org/10.1073/pnas.2026169118 Text en Copyright © 2021 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Kuleta, Patryk
Lasham, Jonathan
Sarewicz, Marcin
Ekiert, Iwona
Sharma, Vivek
Ekiert, Robert
Osyczka, Artur
Hydrogen bonding rearrangement by a mitochondrial disease mutation in cytochrome bc(1) perturbs heme b(H) redox potential and spin state
title Hydrogen bonding rearrangement by a mitochondrial disease mutation in cytochrome bc(1) perturbs heme b(H) redox potential and spin state
title_full Hydrogen bonding rearrangement by a mitochondrial disease mutation in cytochrome bc(1) perturbs heme b(H) redox potential and spin state
title_fullStr Hydrogen bonding rearrangement by a mitochondrial disease mutation in cytochrome bc(1) perturbs heme b(H) redox potential and spin state
title_full_unstemmed Hydrogen bonding rearrangement by a mitochondrial disease mutation in cytochrome bc(1) perturbs heme b(H) redox potential and spin state
title_short Hydrogen bonding rearrangement by a mitochondrial disease mutation in cytochrome bc(1) perturbs heme b(H) redox potential and spin state
title_sort hydrogen bonding rearrangement by a mitochondrial disease mutation in cytochrome bc(1) perturbs heme b(h) redox potential and spin state
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379992/
https://www.ncbi.nlm.nih.gov/pubmed/34389670
http://dx.doi.org/10.1073/pnas.2026169118
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