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Terminal Electron–Proton Transfer Dynamics in the Quinone Reduction of Respiratory Complex I
- Gamiz-Hernandez, Ana P., Jussupow, Alexander, Johansson, Mikael P., Kaila, Ville R. I.
- Journal of the American Chemical Society 2017 v.139 no.45 pp. 16282-16288
- Gibbs free energy, active sites, electron transfer, energy, histidine, hydrogen bonding, menaquinones, molecular dynamics, proton pump, redox potential, tyrosine, ubiquinones
- Complex I functions as a redox-driven proton pump in aerobic respiratory chains. By reducing quinone (Q), complex I employs the free energy released in the process to thermodynamically drive proton pumping across its membrane domain. The initial Q reduction step plays a central role in activating the proton pumping machinery. In order to probe the energetics, dynamics, and molecular mechanism for the proton-coupled electron transfer process linked to the Q reduction, we employ here multiscale quantum and classical molecular simulations. We identify that both ubiquinone (UQ) and menaquinone (MQ) can form stacking and hydrogen-bonded interactions with the conserved Q-binding-site residue His-38 and that conformational changes between these binding modes modulate the Q redox potentials and the rate of electron transfer (eT) from the terminal N2 iron–sulfur center. We further observe that, while the transient formation of semiquinone is not proton-coupled, the second eT process couples to a semiconcerted proton uptake from conserved tyrosine (Tyr-87) and histidine (His-38) residues within the active site. Our calculations indicate that both UQ and MQ have low redox potentials around −260 and −230 mV, respectively, in the Q-binding site, respectively, suggesting that release of the Q toward the membrane is coupled to an energy transduction step that could thermodynamically drive proton pumping in complex I.