Proton pumping mechanism and catalytic cycle of cytochrome <i>c</i> oxidase: Coulomb pump model with kinetic gating

Popović, Dragan M.; Stuchebrukhov, Alexei A.

doi:10.1016/j.febslet.2004.04.016

Cited by 118 publications

(139 citation statements)

References 34 publications

Supporting

Mentioning

133

Contrasting

Order By: Relevance

“…More generally, one finds that for the commonly used continuum parameters, 3,21,40,44 the sum of the probe and atomic radius significantly exceeds the equilibrium interatomic distance between given protein atom and water oxygen observed in the x-ray data. The reason for this is that internal water molecules form strong hydrogen bonds with protein structure, 6,7 but commonly used parameters do not properly take into account this effect.…”

Section: Optimal Atomic Radii For a Standard Probe Radiusmentioning

confidence: 99%

“…Thus, the free energy change due to introduced charges consists of two parts: The protein field term, representing the work needed to transfer charges ⌬q i from infinity to the corresponding atomic positions of the solute at fixed ͑equilibrium͒ nuclear positions of the latter, and the reaction-field term, representing the free energy change due to the relaxation of the equilibrium atomic positions in response to the introduced charges. In the literature, ⌬G prot and ⌬G rf are also called as the protein field and Born term, 3,21,35,36 static and relaxation term, 14,15,17 or as the interaction and self-energy terms, 4,25,27 respectively. In this paper, we will be interested only in ⌬G rf term which reflects the dielectric relaxation of the protein medium.…”

Section: ͑2͒mentioning

confidence: 99%

“…20,21 In CcO, there are a lot of internal water molecules which significantly affect the functionality of the enzyme and its dielectric properties.…”

Section: Introductionmentioning

confidence: 99%

“…The values of such parameters are often different in different studies, which is one of the reasons for the differences in the pK a calculations of the enzyme. 3,21,22 The key parameter appears to be the dielectric constant of the enzyme water cavities cav , about which very little is known. Although it is well recognized that different cavities may have different dielectric properties ͑e.g., size dependent͒, it is important to know typical magnitudes of their dielectric relaxation parameters.…”

Section: Introductionmentioning

confidence: 99%

“…This residue is a key element of a recently proposed proton pumping mechanism of the enzyme. 3,21 The dielectric constant of the protein p and that of an important water cavity cav in the vicinity of the catalytic center ͑see Fig. 1͒ are determined as adjustable parameters which reproduce the microscopic reaction-field energy of charging ͑or deprotonation͒ obtained in MD simulations of the dry protein and the protein with internal water.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Dielectric relaxation of cytochrome c oxidase: Comparison of the microscopic and continuum models

Leontyev

Stuchebrukhov

2009

The Journal of Chemical Physics

View full text Add to dashboard Cite

We have studied a charge-insertion process that models the deprotonation of a histidine side chain in the active site of cytochrome c oxidase ͑CcO͒ using both the continuum electrostatic calculations and the microscopic simulations. The group of interest is a ligand to Cu B center of CcO, which has been previously suggested to play the role of the proton pumping element in the enzyme; the group is located near a large internal water cavity in the protein. Using the nonpolarizable Amber-99 force field in molecular dynamics ͑MD͒ simulations, we have calculated the nuclear part of the reaction-field energy of charging of the His group and combined it with the electronic part, which we estimated in terms of the electronic continuum ͑EC͒ model, to obtain the total reaction-field energy of charging. The total free energy obtained in this MDEC approach was then compared with that calculated using pure continuum electrostatic model with variable dielectric parameters. The dielectric constant for the "dry" protein and that of the internal water cavity of CcO were determined as those parameters that provide best agreement between the continuum and microscopic MDEC model. The nuclear ͑MD͒ polarization alone ͑without electronic part͒ of a dry protein was found to correspond to an unphysically low dielectric constant of only about 1.3, whereas the inclusion of electronic polarizability increases the protein dielectric constant to 2.6-2.8. A detailed analysis is presented as to how the protein structure should be selected for the continuum calculations, as well as which probe and atomic radii should be used for cavity definition. The dielectric constant of the internal water cavity was found to be 80 or even higher using "standard" parameters of water probe radius, 1.4 Å, and protein atomic radii from the MD force field for cavity description; such high values are ascribed to the fact that the standard procedure produces unphysically small cavities. Using x-ray data for internal water in CcO, we have explored optimization of the parameters and the algorithm of cavity description. For Amber radii, the optimal probe size was found to be 1.25 Å; the dielectric of water cavity in this case is in the range of 10-16. The most satisfactory cavity description, however, was achieved with ProtOr atomic radii, while keeping the probe radius to be standard 1.4 Å. In this case, the value of cavity dielectric constant was found to be in the range of 3-6. The obtained results are discussed in the context of recent calculations and experimental measurements of dielectric properties of proteins.

show abstract

Section: Optimal Atomic Radii For a Standard Probe Radiusmentioning

confidence: 99%

Section: ͑2͒mentioning

confidence: 99%

“…20,21 In CcO, there are a lot of internal water molecules which significantly affect the functionality of the enzyme and its dielectric properties.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Dielectric relaxation of cytochrome c oxidase: Comparison of the microscopic and continuum models

Leontyev

Stuchebrukhov

2009

The Journal of Chemical Physics

View full text Add to dashboard Cite

show abstract

Combined Density Functional Theory ( DFT ) and Electrostatics Study of the Proton Pumping Mechanism in Cytochrome C Oxidase

Quenneville

Popović

Stuchebrukhov

2005

Encyclopedia of Inorganic Chemistry

View full text Add to dashboard Cite

Cytochrome c oxidase is a redox‐driven proton pump which converts atmospheric oxygen to water and couples the oxygen reduction reaction to the creation of a membrane proton gradient. The structure of the enzyme has been solved; however, the mechanism of proton pumping is still poorly understood. Recent calculations from this group indicate that one of the histidine ligands of the enzyme's Cu B center, His291, may play the role of the pumping element. Here, we discuss results of calculations that combined first principles density functional theory (DFT) and continuum electrostatics to evaluate the energetics of the key energy generating step—the transfer of the chemical proton to the binuclear center of the enzyme, where the hydroxyl group is converted to water, and the concerted expulsion of the proton from d‐nitrogen of the His291 ligand of the Cu B center.

show abstract

Role of the tightly bound quinone for the oxygen reaction of cytochrome bo₃ oxidase from Escherichia coli

et al. 2018

View full text Add to dashboard Cite

The coupling of the reaction of a tightly bound ubiquinone with the reduction of O2 in cytochrome bo3 of Escherichia coli was investigated. In the absence of the quinone, a strongly diminished rate of electrocatalytic reduction of oxygen is detected, which can be restored by adding quinones. The correlation of previous EPR data with the electrocatalytic study on mutations in the binding site at positions, Q101, D75, F93, H98, I102 and R71 reveal that the stabilization of the radical is not necessary for the oxygen reaction. The Q101 and F93 variants exhibit both well‐defined catalytic i–V curves, whereas D75H, H98F, I102W and R71H exhibit broad i–V curves with large hysteresis pointing toward a strong alteration in their catalytic activity.

show abstract

Proton pumping mechanism and catalytic cycle of cytochrome c oxidase: Coulomb pump model with kinetic gating

Cited by 118 publications

References 34 publications

Dielectric relaxation of cytochrome c oxidase: Comparison of the microscopic and continuum models

Dielectric relaxation of cytochrome c oxidase: Comparison of the microscopic and continuum models

Combined Density Functional Theory ( DFT ) and Electrostatics Study of the Proton Pumping Mechanism in Cytochrome C Oxidase

Role of the tightly bound quinone for the oxygen reaction of cytochrome bo₃ oxidase from Escherichia coli

Contact Info

Product

Resources

About

Proton pumping mechanism and catalytic cycle of cytochrome c oxidase: Coulomb pump model with kinetic gating

Cited by 118 publications

References 34 publications

Dielectric relaxation of cytochrome c oxidase: Comparison of the microscopic and continuum models

Dielectric relaxation of cytochrome c oxidase: Comparison of the microscopic and continuum models

Combined Density Functional Theory ( DFT ) and Electrostatics Study of the Proton Pumping Mechanism in Cytochrome C Oxidase

Role of the tightly bound quinone for the oxygen reaction of cytochrome bo3 oxidase from Escherichia coli

Contact Info

Product

Resources

About

Role of the tightly bound quinone for the oxygen reaction of cytochrome bo₃ oxidase from Escherichia coli