Proton‐Coupled Electron Transfer in Cytochrome c Oxidase: Heme a Controls the Protonation Dynamics of E286
Year: 2025
Type: article
Abstract: Complex IV of the mitochondrial respiratory chain, or cytochrome c oxidase (C c O), contributes to the proton motive force necessary for ATP synthesis. C c O can slow the formation of reactive oxygen species and is key to physiology and drug development. The exact molecular mechanisms underlying its proton‐pumping function remain elusive. The redox state of C c O's metallic cofactors is intimately connected to structural changes and proton pumping via proton‐coupled electron transfer. Time‐resolved UV/Vis and IR spectroscopy are used to investigate the effects of the electronic backreaction triggered by photolyzing the CO‐inhibited 2‐electron reduced state, R 2 CO , in the aa 3 oxidase from Cereibacter sphaeroides . An intermediate is identified, in which the binuclear center matches the redox state of the catalytic intermediate E (one‐electron reduced state), with a rise time of ≈2 μs. The electron transfer induces structural changes that lead to E286 deprotonation, with a time constant of 13 μs. Thus, it is inferred that transient reduction of heme a alone drives E286 deprotonation. E286 is reprotonated with a time constant of 72 ms when CO rebinds. The results support the view that transient heme a reduction in the physiological E state modulates the electrostatic environment, triggering proton transfer toward the proton‐loading site.
Source: ChemPhysChem
Authors: Federico Baserga, Pit Langner, Luiz Schubert, Julian P. Storm, Ramona Schlesinger, Joachim Heberle
Institution: Freie Universität Berlin
Language: English
Subfield: Inorganic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,550
OpenAlex ID: W4416026601