Insights into proton translocation in cbb3 oxidase from MD simulations

Catarina A. Carvalheda (Lead / Corresponding author), Andrei V. Pisliakov (Lead / Corresponding author)

Research output: Contribution to journalArticle

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Abstract

Heme-copper oxidases are membrane protein complexes that catalyse the final step of the aerobic respiration, namely the reduction of oxygen to water. The energy released during catalysis is coupled to the active translocation of protons across the membrane, which contributes to the establishment of an electrochemical gradient that is used for ATP synthesis. The distinctive C-type (or cbb3) cytochrome c oxidases, which are mostly present in proteobacteria, exhibit a number of unique structural and functional features, including high catalytic activity at low oxygen concentrations. At the moment, the functioning mechanism of C-type oxidases, in particular the proton transfer/pumping mechanism presumably via a single proton channel, is still poorly understood. In this work we used all-atom molecular dynamics simulations and continuum electrostatics calculations to obtain atomic-level insights into the hydration and dynamics of a cbb3 oxidase. We provide the details of the water dynamics and proton transfer pathways for both the “chemical” and “pumped” protons, and show that formation of protonic connections is strongly affected by the protonation state of key residues, namely H243, E323 and H337.
Original languageEnglish
Pages (from-to)396-406
Number of pages11
JournalBiochimica et Biophysica Acta (BBA) - Bioenergetics
Volume1858
Issue number5
Early online date1 Mar 2017
DOIs
Publication statusPublished - May 2017

Fingerprint

Protons
Proton transfer
Oxygen
Water
Protonation
Electron Transport Complex IV
Heme
Hydration
Catalysis
Molecular dynamics
Electrostatics
Catalyst activity
Oxidoreductases
Membrane Proteins
Proteobacteria
Adenosine Triphosphate
Membranes
Molecular Dynamics Simulation
Atoms
Static Electricity

Keywords

  • molecular dynamics simulations
  • pKa calculations
  • proton transfer
  • water dynamics
  • cytochrome c oxidase
  • proton pump
  • membrane protein

Cite this

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title = "Insights into proton translocation in cbb3 oxidase from MD simulations",
abstract = "Heme-copper oxidases are membrane protein complexes that catalyse the final step of the aerobic respiration, namely the reduction of oxygen to water. The energy released during catalysis is coupled to the active translocation of protons across the membrane, which contributes to the establishment of an electrochemical gradient that is used for ATP synthesis. The distinctive C-type (or cbb3) cytochrome c oxidases, which are mostly present in proteobacteria, exhibit a number of unique structural and functional features, including high catalytic activity at low oxygen concentrations. At the moment, the functioning mechanism of C-type oxidases, in particular the proton transfer/pumping mechanism presumably via a single proton channel, is still poorly understood. In this work we used all-atom molecular dynamics simulations and continuum electrostatics calculations to obtain atomic-level insights into the hydration and dynamics of a cbb3 oxidase. We provide the details of the water dynamics and proton transfer pathways for both the “chemical” and “pumped” protons, and show that formation of protonic connections is strongly affected by the protonation state of key residues, namely H243, E323 and H337.",
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author = "Carvalheda, {Catarina A.} and Pisliakov, {Andrei V.}",
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Insights into proton translocation in cbb3 oxidase from MD simulations. / Carvalheda , Catarina A. (Lead / Corresponding author); Pisliakov, Andrei V. (Lead / Corresponding author).

In: Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1858, No. 5, 05.2017, p. 396-406.

Research output: Contribution to journalArticle

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T1 - Insights into proton translocation in cbb3 oxidase from MD simulations

AU - Carvalheda , Catarina A.

AU - Pisliakov, Andrei V.

N1 - This work was funded by the Scottish Universities Physics Alliance (SUPA). We also appreciate support from the University of Dundee Life Sciences Computing cluster. Access to ARCHER National Supercomputing Service was provided through the HEC-Biosim Consortium.

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N2 - Heme-copper oxidases are membrane protein complexes that catalyse the final step of the aerobic respiration, namely the reduction of oxygen to water. The energy released during catalysis is coupled to the active translocation of protons across the membrane, which contributes to the establishment of an electrochemical gradient that is used for ATP synthesis. The distinctive C-type (or cbb3) cytochrome c oxidases, which are mostly present in proteobacteria, exhibit a number of unique structural and functional features, including high catalytic activity at low oxygen concentrations. At the moment, the functioning mechanism of C-type oxidases, in particular the proton transfer/pumping mechanism presumably via a single proton channel, is still poorly understood. In this work we used all-atom molecular dynamics simulations and continuum electrostatics calculations to obtain atomic-level insights into the hydration and dynamics of a cbb3 oxidase. We provide the details of the water dynamics and proton transfer pathways for both the “chemical” and “pumped” protons, and show that formation of protonic connections is strongly affected by the protonation state of key residues, namely H243, E323 and H337.

AB - Heme-copper oxidases are membrane protein complexes that catalyse the final step of the aerobic respiration, namely the reduction of oxygen to water. The energy released during catalysis is coupled to the active translocation of protons across the membrane, which contributes to the establishment of an electrochemical gradient that is used for ATP synthesis. The distinctive C-type (or cbb3) cytochrome c oxidases, which are mostly present in proteobacteria, exhibit a number of unique structural and functional features, including high catalytic activity at low oxygen concentrations. At the moment, the functioning mechanism of C-type oxidases, in particular the proton transfer/pumping mechanism presumably via a single proton channel, is still poorly understood. In this work we used all-atom molecular dynamics simulations and continuum electrostatics calculations to obtain atomic-level insights into the hydration and dynamics of a cbb3 oxidase. We provide the details of the water dynamics and proton transfer pathways for both the “chemical” and “pumped” protons, and show that formation of protonic connections is strongly affected by the protonation state of key residues, namely H243, E323 and H337.

KW - molecular dynamics simulations

KW - pKa calculations

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KW - cytochrome c oxidase

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