Kinetics of the Terminal Electron Transfer Step in Cytochrome c Oxidase

• Published in: The journal of physical chemistry. B Vol. 116; no. 6; pp. 1876 - 1883
• Main Authors: Tipmanee, Varomyalin, Blumberger, Jochen
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 16.02.2012
• Subjects: cytochrome-c oxidase; Cytochromes; Electron transfer; Electron Transport; Electron Transport Complex IV - chemistry; Electron Transport Complex IV - metabolism; Electronics; Electrons; equations; Free energy; Gibbs free energy; heme; Heme - chemistry; Kinetics; Mathematical analysis; molecular dynamics; Molecular Dynamics Simulation; Oxidase; Oxidation-Reduction; oxygen; Protein Structure, Tertiary; Proteins; temperature; Terminals; Thermodynamics
• ISSN: 1520-6106; 1520-5207; 1520-5207
• DOI: 10.1021/jp209175j

Cytochrome c oxidase (cco) catalyzes the oxygen reduction reaction in most aerobically respiring organisms. Decades of research have uncovered many aspects relating to structure and function of this enzyme. However, the origin of the unusually fast terminal electron transfer step from heme a to heme a3 in cco has been the subject of intense discussions over recent years. Yet, no satisfactory consensus has been achieved. Carrying out large-scale molecular dynamics simulation of the protein embedded in a solvated membrane, we obtain a reorganization free energy λ = 0.57 eV. Evaluation of the quantized single-mode rate equation using the experimental rate and the computed reorganization free energy gives a value of 1.5 meV for the average electronic coupling (H ab) between heme a and heme a3. Thus, according to our calculations, the nanosecond electron transfer (ET) is due to a small but significant activation barrier (ΔG ‡ = 0.12 eV) in combination with effective electronic coupling between the two cofactors. The activation free energy is caused predominantly by collective reorganization of protein residues. We show that our results are consistent with the weak temperature dependence observed in experiment if one allows for very minor variations in the donor–acceptor distance as the temperature changes.