New insights into the proton pumping mechanism of ba<sub>3</sub> cytochrome <i>c</i> oxidase: the functions of key residues and water

Yang, Xiaoyue; Liu, Shaohui; Yin, Zhili; Chen, Mengguo; Song, Jinshuai; Li, Pengfei; Yang, Longhua

doi:10.1039/d3cp01334k

Cited by 3 publications

(1 citation statement)

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“…In a very recent work, Yang et al (2023) have analyzed the effects of some of these site-directed mutants of ba 3 CcO on the proton exit pathways using electrostatics and MD methods closely related to those we used in our collaborative work on the native enzyme (Yang et al, 2016a). The authors find that often site-directed mutations change structures of adjacent residue sidechains and that the water pathways are shifted often, consistent with our speculations mentioned above.…”

Section: Additional Connections To the Literature On Cytochrome Ba 3 ...supporting

confidence: 74%

Reaction pathways, proton transfer, and proton pumping in ba3 class cytochrome c oxidase: perspectives from DFT quantum chemistry and molecular dynamics

Noodleman,

Götz,

Han Du

et al. 2023

Front. Chem.

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After drawing comparisons between the reaction pathways of cytochrome c oxidase (CcO, Complex 4) and the preceding complex cytochrome bc1 (Complex 3), both being proton pumping complexes along the electron transport chain, we provide an analysis of the reaction pathways in bacterial ba3 class CcO, comparing spectroscopic results and kinetics observations with results from DFT calculations. For an important arc of the catalytic cycle in CcO, we can trace the energy pathways for the chemical protons and show how these pathways drive proton pumping of the vectorial protons. We then explore the proton loading network above the Fe heme a3–CuB catalytic center, showing how protons are loaded in and then released by combining DFT-based reaction energies with molecular dynamics simulations over states of that cycle. We also propose some additional reaction pathways for the chemical and vector protons based on our recent work with spectroscopic support.

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Section: Additional Connections To the Literature On Cytochrome Ba 3 ...supporting

confidence: 74%

Reaction pathways, proton transfer, and proton pumping in ba3 class cytochrome c oxidase: perspectives from DFT quantum chemistry and molecular dynamics

Noodleman,

Götz,

Han Du

et al. 2023

Front. Chem.

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Mammalian copper homeostasis: physiological roles and molecular mechanisms

Lutsenko,

Roy,

Tsvetkov

2025

Physiological Reviews

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In the past decade, evidence for numerous roles of copper (Cu) in mammalian physiology has grown exponentially. The discoveries of Cu involvement in cell signaling, autophagy, cell motility, differentiation, and regulated cell death (cuproptosis) have markedly extended the list of already known functions of Cu, such as a cofactor of essential metabolic enzymes, a protein structural component, and a regulator of protein trafficking. Novel and unexpected functions of Cu transporting proteins and enzymes have been identified, and new disorders of Cu homeostasis have been described. Significant progress has been made in the mechanistic studies of two classic disorders of Cu metabolism, Menkes disease and Wilson disease, which paved ways to novel approaches to their treatment. Discovery of cuproptosis and the role of Cu in cells metastatic growth have markedly increased interest in targeting Cu homeostatic pathways to treat cancer. In this review, we summarize the established concepts in the field of mammalian Cu physiology, and discuss how new discoveries of the past decade expand and modify these concepts. The roles of Cu in brain metabolism, in cells' functional speciation and a recently discovered regulated cell death have attracted significant attention and are highlighted in this review.

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Membrane-Bound Redox Enzyme Cytochrome bd-I Promotes Carbon Monoxide-Resistant Escherichia coli Growth and Respiration

Nastasi,

Borisov,

Forte

2024

IJMS

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The terminal oxidases of bacterial aerobic respiratory chains are redox-active electrogenic enzymes that catalyze the four-electron reduction of O2 to 2H2O taking out electrons from quinol or cytochrome c. Living bacteria often deal with carbon monoxide (CO) which can act as both a signaling molecule and a poison. Bacterial terminal oxidases contain hemes; therefore, they are potential targets for CO. However, our knowledge of this issue is limited and contradictory. Here, we investigated the effect of CO on the cell growth and aerobic respiration of three different Escherichia coli mutants, each expressing only one terminal quinol oxidase: cytochrome bd-I, cytochrome bd-II, or cytochrome bo3. We found that following the addition of CO to bd-I-only cells, a minimal effect on growth was observed, whereas the growth of both bd-II-only and bo3-only strains was severely impaired. Consistently, the degree of resistance of aerobic respiration of bd-I-only cells to CO is high, as opposed to high CO sensitivity displayed by bd-II-only and bo3-only cells consuming O2. Such a difference between the oxidases in sensitivity to CO was also observed with isolated membranes of the mutants. Accordingly, O2 consumption of wild-type cells showed relatively low CO sensitivity under conditions favoring the expression of a bd-type oxidase.

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New insights into the proton pumping mechanism of ba₃ cytochrome c oxidase: the functions of key residues and water

Abstract: As the terminal oxidase of cell respiration in mitochondria and aerobic bacteria, the proton pumping mechanism of ba3-type Cytochrome c Oxidase (CcO) of Thermus thermophiles is still not fully understood....

Cited by 3 publications

References 69 publications

Reaction pathways, proton transfer, and proton pumping in ba3 class cytochrome c oxidase: perspectives from DFT quantum chemistry and molecular dynamics

Reaction pathways, proton transfer, and proton pumping in ba3 class cytochrome c oxidase: perspectives from DFT quantum chemistry and molecular dynamics

Mammalian copper homeostasis: physiological roles and molecular mechanisms

Membrane-Bound Redox Enzyme Cytochrome bd-I Promotes Carbon Monoxide-Resistant Escherichia coli Growth and Respiration

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New insights into the proton pumping mechanism of ba3 cytochrome c oxidase: the functions of key residues and water

Abstract: As the terminal oxidase of cell respiration in mitochondria and aerobic bacteria, the proton pumping mechanism of ba3-type Cytochrome c Oxidase (CcO) of Thermus thermophiles is still not fully understood....

Cited by 3 publications

References 69 publications

Reaction pathways, proton transfer, and proton pumping in ba3 class cytochrome c oxidase: perspectives from DFT quantum chemistry and molecular dynamics

Reaction pathways, proton transfer, and proton pumping in ba3 class cytochrome c oxidase: perspectives from DFT quantum chemistry and molecular dynamics

Mammalian copper homeostasis: physiological roles and molecular mechanisms

Membrane-Bound Redox Enzyme Cytochrome bd-I Promotes Carbon Monoxide-Resistant Escherichia coli Growth and Respiration

Contact Info

Product

Resources

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New insights into the proton pumping mechanism of ba₃ cytochrome c oxidase: the functions of key residues and water