Pathways for electron tunneling in cytochrome c oxidase

• Published in: Journal of bioenergetics and biomembranes 1998-02, Vol.30 (1), p.35-39
• Main Authors: Regan, J J, Ramirez, B E, Winkler, J R, Gray, H B, Malmström, B G
• Format: Article
• Language: English
• Subjects: Animals; Bioenergetics; Crystal structure; Cytochrome; Electron Transport; Electron Transport Complex IV - metabolism; Enzymes; Humans; Photochemicals; Proteins; Protons; Sulfur
• ISSN: 0145-479X; 1573-6881
• DOI: 10.1023/a:1020551326307

Warburg showed in 1929 that the photochemical action spectrum for CO dissociation from cytochrome c oxidase is that of a heme protein. Keilin had shown that cytochrome a does not react with oxygen, so he did not accept Warburg's view until 1939, when he discovered cytochrome a3. The dinuclear cytochrome a3-CuB unit was found by EPR in 1967, whereas the dinuclear nature of the CuA site was not universally accepted until oxidase crystal structures were published in 1995. There are negative redox interactions between cytochrome a and the other redox sites in the oxidase, so that the reduction potential of a particular site depends on the redox states of the other sites. Calculated electron-tunneling pathways for internal electron transfer in the oxidase indicate that the coupling-limited rates are 9 x 10(5) (CuA-->a) and 7 x 10(6) s(-1) (a-->a3); these calculations are in reasonable agreement with experimental rates, after corrections are made for driving force and reorganization energy. The best CuA-a pathway starts from the ligand His204 and not from the bridging sulfur of Cys196, and an efficient a-a3 path involves the heme ligands His378 and His376 as well as the intervening Phe377 residue. All direct paths from CuA to a3 are poor, indicating that direct CuA-->a3 electron transfer is much slower than the CuA-->a reaction. The pathways model suggests a means for gating the electron flow in redox-linked proton pumps.