8GVM

The structure of azide-bound cytochrome C oxidase determined using the crystals exposed to 20 mm azide solution for 4 days

Summary for 8GVM

• Entry DOI: 10.2210/pdb8gvm/pdb
• Descriptor: Cytochrome c oxidase subunit 1, Cytochrome c oxidase subunit 7A1, Cytochrome c oxidase subunit 7B, mitochondrial, ... (29 entities in total)
• Functional Keywords: metalloenzyme, cytochrome c oxidase, proton pump, bioenergetics, heme, copper, oxidoreductase
• Biological source: Bos taurus (cattle); More
• Total number of polymer chains: 26
• Total formula weight: 449541.42

Authors

Tsukihara, T.,Shimada, A. (deposition date: 2022-09-15, release date: 2022-10-19, Last modification date: 2023-11-29)

Primary citation

Shimada, A.,Hatano, K.,Tadehara, H.,Yano, N.,Sinzawa-Itoh, K.,Yamashita, E.,Mutamoto, K.,Tsukihara, T.,Yoshikawa, S.
X-ray structural analyses of azide-bound cytochromecoxidases reveal that the H-pathway is critically important for the proton-pumping activity
J. Biol. Chem., 293:14868-14879, 2018

PubMed Abstract: Cytochrome oxidase (CcO) is the terminal oxidase of cellular respiration, reducing O to water and pumping protons. X-ray structural features have suggested that CcO pumps protons via a mechanism involving electrostatic repulsions between pumping protons in the hydrogen-bond network of a proton-conducting pathway (the H-pathway) and net positive charges created upon oxidation of an iron site, heme (Fe ), for reduction of O at another iron site, heme (Fe ). The protons for pumping are transferred to the hydrogen-bond network from the N-side via the water channel of the H-pathway. Back-leakage of protons to the N-side is thought to be blocked by closure of the water channel. To experimentally test this, we examined X-ray structures of the azide-bound, oxidized bovine CcO and found that an azide derivative (N-Fe , Cu-N) induces a translational movement of the heme plane. This was accompanied by opening of the water channel, revealing that Fe and the H-pathway are tightly coupled. The channel opening in the oxidized state is likely to induce back-leakage of pumping protons, which lowers the proton level in the hydrogen-bond network during enzymatic turnover. The proton level decrease weakens the electron affinity of Fe , if Fe electrostatically interacts with protons in the hydrogen-bond network. The previously reported azide-induced redox-potential decrease in Fe supports existence of the electrostatic interaction. In summary, our results indicate that the H-pathway is critical for CcO's proton-pumping function.

PubMed: 30077971
DOI: 10.1074/JBC.RA118.003123

Experimental method

X-RAY DIFFRACTION (1.851 Å)