Coupled electron and proton transfer reactions during the O → E transition in bovine cytochrome c oxidase

► DFT/electrostatic method is used to study proton pumping in cytochrome oxidase. ► Novel features of His291 pumping model are considered. ► The coupling of PT from Glu242 to His291 to ET between the hemes is discussed. ► The pKas and Ems of the key ionizable and redox groups are evaluated.