Charge parameterization of the metal centers in cytochrome <i>c</i> oxidase

Johansson, Mikael P.; Kaila, Ville R. I.; Laakkonen, Liisa

doi:10.1002/jcc.20835

Cited by 50 publications

(51 citation statements)

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“…However, it is also likely that stabilization of local hydrogen bonds assists in further stabilization of water chains upon changes in redox states. For instance, the partial charge on the oxygen atom ligating Cu B changes from −0.66e to −0.80e upon reduction (P M ' → P R ) (21), which may strengthen the hydrogen bond with the nearest water molecule. This stabilization would then affect the entire water chain up to the terminal proton donor Glu242 due to cooperative hydrogen bonding effects among water molecules (22,23).…”

Section: Resultsmentioning

confidence: 99%

“…The protonation states of BNC ligands were decided on the basis of available experimental data (3) and previous density functional theory (DFT) calculations performed on cluster systems (3,21,26). It is known based on spectroscopic measurements that all P and F variants have a ferryl heme a 3 (3,14) except for the postulated state F R , which has ferric heme a 3 ligated by a hydroxyl ion (26).…”

Section: Methodsmentioning

confidence: 99%

“…Asp364, which forms a hydrogen bond with the A-propionate of high-spin heme, was also kept protonated based on DFT calculation data (21,30). The cross-linked tyrosine, which supplies a proton and an electron in the early phase of the catalytic cycle (Fig.…”

Section: Methodsmentioning

confidence: 99%

“…The charges and parameters of standard amino acid residues were obtained from the Chemistry at Harvard Macromolecular Mechanics (CHARMM) force field (40), and for metal centers, charges and parameters were obtained from previous studies (21,26). After construction of the protein system, it was immersed in a lipid bilayer comprising cardiolipin (CL), phosphatidylcholine (PC), and phosphatidylethanolamine (PE) molecules.…”

Section: Methodsmentioning

confidence: 99%

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Proton-coupled electron transfer and the role of water molecules in proton pumping by cytochrome c oxidase

Sharma

Enkavi

Vattulainen

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Molecular oxygen acts as the terminal electron sink in the respiratory chains of aerobic organisms. Cytochrome c oxidase in the inner membrane of mitochondria and the plasma membrane of bacteria catalyzes the reduction of oxygen to water, and couples the free energy of the reaction to proton pumping across the membrane. The proton-pumping activity contributes to the proton electrochemical gradient, which drives the synthesis of ATP. Based on kinetic experiments on the O-O bond splitting transition of the catalytic cycle (A → P R ), it has been proposed that the electron transfer to the binuclear iron-copper center of O 2 reduction initiates the proton pump mechanism. This key electron transfer event is coupled to an internal proton transfer from a conserved glutamic acid to the proton-loading site of the pump. However, the proton may instead be transferred to the binuclear center to complete the oxygen reduction chemistry, which would constitute a short-circuit. Based on atomistic molecular dynamics simulations of cytochrome c oxidase in an explicit membrane-solvent environment, complemented by related free-energy calculations, we propose that this short-circuit is effectively prevented by a redoxstate-dependent organization of water molecules within the protein structure that gates the proton transfer pathway.cell respiration | atomistic molecular dynamics simulations | functional water molecules | free-energy calculations

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Proton-coupled electron transfer and the role of water molecules in proton pumping by cytochrome c oxidase

Sharma

Enkavi

Vattulainen

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…The four states are denoted: P R , P′ R , P″ R , and ′F. Analyses considering different force field parameters (27,35), including the effect of electronic polarization (16), and conditions for the MD simulations test the robustness of the results (SI Appendix).…”

Section: Resultsmentioning

confidence: 99%

Changing hydration level in an internal cavity modulates the proton affinity of a key glutamate in cytochromecoxidase

Goyal

Yang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

112

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Cytochrome c oxidase contributes to the transmembrane proton gradient by removing two protons from the high-pH side of the membrane each time the binuclear center active site is reduced. One proton goes to the binuclear center, whereas the other is pumped to the low-pH periplasmic space. Glutamate 286 (Glu286) has been proposed to serve as a transiently deprotonated proton donor. Using unrestrained atomistic molecular dynamics simulations, we show that the size of and water distribution in the hydrophobic cavity that holds Glu286 is controlled by the protonation state of the propionic acid of heme a 3 , a group on the proton outlet pathway. Protonation of the propionate disrupts hydrogen bonding to two side chains, allowing a loop to swing open. Continuum electrostatics and atomistic free-energy perturbation calculations show that the resultant changes in hydration and electrostatic interactions lower the Glu proton affinity by at least 5 kcal/mol. These changes in the internal hydration level occur in the absence of major conformational transitions and serve to stabilize needed transient intermediates in proton transport. The trigger is not the protonation of the Glu of interest, but rather the protonation of a residue ∼10 Å away. Thus, unlike local water penetration to stabilize a new charge, this finding represents a specific role for water molecules in the protein interior, mediating proton transfers and facilitating ion transport.proton pumping | pK a W ater is essential to the structure, dynamics, and function of biomolecules (1, 2), and its role in protein folding, association (3), and dynamics (4, 5) has been well documented. The highly polar and polarizable water molecules play diverse roles in protein interiors. Water can aid catalysis in enzyme active sites (6-8). Water or water chains are often observed in proteins that are (9, 10) proton or ion transporters or pumps (11)(12)(13)(14). Internal cavities holding functional water molecules are believed to have a fairly constant level of hydration throughout the protein reaction cycle, unless significant conformational changes occur (15). Water penetration in response to the ionization or reduction of internal groups has been extensively discussed (16,17), although it is usually described as part of protein's local dielectric response.Cytochrome c oxidase (CcO) adds to the transmembrane proton gradient through proton transport coupled to electron transfer reactions (12,18,19). In the overall reaction, electrons from four cytochromes c are transferred to oxygen to make two water molecules at the binuclear center (BNC). The four protons needed for chemistry are bound only from the high-pH, N side of the membrane. Coupled to the process, four more protons are transferred across the membrane from the high-to low-pH (P) side of the membrane. Thus, eight charges are transferred across the membrane as each O 2 is reduced.Glu286 is a required, conserved residue that is expected to transfer protons from the D channel either to the BNC or the proton-loading site (...

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Piezoelectricity of the Transmembrane Protein ba₃ Cytochrome c Oxidase

O'Donnell

Cazade

Guerin

et al. 2021

Adv Funct Materials

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Controlling the electromechanical response of piezoelectric biological structures including tissues, peptides, and amino acids provides new applications for biocompatible, sustainable materials in electronics and medicine. Here, the piezoelectric effect is revealed in another class of biological materials, with robust longitudinal and shear piezoelectricity measured in single crystals of the transmembrane protein ba3 cytochrome c oxidase from Thermus thermophilus. The experimental findings from piezoresponse force microscopy are substantiated using a range of control measurements and molecular models. The observed longitudinal and shear piezoelectric responses of ≈2 and 8 pm V−1, respectively, are comparable to or exceed the performance of commonly used inorganic piezoelectric materials including quartz, aluminum nitride, and zinc oxide. This suggests that transmembrane proteins may provide, in addition to physiological energy transduction, technologically useful piezoelectric material derived entirely from nature. Membrane proteins could extend the range of rationally designed biopiezoelectric materials far beyond the minimalistic peptide motifs currently used in miniaturized energy harvesters, and the finding of robust piezoelectric response in a transmembrane protein also raises fundamental questions regarding the molecular evolution, activation, and role of regulatory proteins in the cellular nanomachinery, indicating that piezoelectricity might be important for fundamental physiological processes.

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Charge parameterization of the metal centers in cytochrome c oxidase

Cited by 50 publications

References 89 publications

Proton-coupled electron transfer and the role of water molecules in proton pumping by cytochrome c oxidase

Proton-coupled electron transfer and the role of water molecules in proton pumping by cytochrome c oxidase

Changing hydration level in an internal cavity modulates the proton affinity of a key glutamate in cytochromecoxidase

Piezoelectricity of the Transmembrane Protein ba₃ Cytochrome c Oxidase

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Charge parameterization of the metal centers in cytochrome c oxidase

Cited by 50 publications

References 89 publications

Proton-coupled electron transfer and the role of water molecules in proton pumping by cytochrome c oxidase

Proton-coupled electron transfer and the role of water molecules in proton pumping by cytochrome c oxidase

Changing hydration level in an internal cavity modulates the proton affinity of a key glutamate in cytochromecoxidase

Piezoelectricity of the Transmembrane Protein ba3 Cytochrome c Oxidase

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Product

Resources

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Piezoelectricity of the Transmembrane Protein ba₃ Cytochrome c Oxidase