Cytochrome c oxidase

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The crystal structure of bovine cytochrome c oxidase in a phospholipid bilayer. The intermembrane space lies to top of the image. Adapted from PDB 1OCC (It is a homo dimer in this structure)

The enzyme cytochrome c oxidase (PDB 2OCC, EC 1.9.3.1) is a large transmembrane protein complex found in bacteria and the mitochondrion. It is the last protein in the electron transport chain. It receives an electron from each of four cytochrome c molecules, and transfers them to one oxygen molecule, converting molecular oxygen to two molecules of water. In the process, it translocates four protons, helping to establish a chemiosmotic potential that the ATP synthase then uses to synthesize ATP.

Summary reaction:

4 Fe²⁺-cytochrome c + 2 H⁺_in + O₂ → 4 Fe³⁺-cytochrome c + 2 H₂O + 4 H⁺_out

The complex is a large lipoprotein composed of several metal prosthetic sites and 13 protein subunits in mammals. In mammals, ten subunits are nuclear in origin and three are synthesized mitochondrially. The complex contains two hemes, the a and a₃ hemes, and two copper centers, the Cu_A and Cu_B centers. In fact, the heme a₃ and Cu_B are a binuclear center that is the site of oxygen reduction. The mechanism of action of this large complex is still an active research topic.

Crystallographic studies of cytochrome c oxidase show an unusual post translational modification, linking C6 of Tyr(244) and the ε-N of His(240) (bovine enzyme numbering). This cross-linked tyrosine has been proposed to serve as a hydrogen donor, providing a proton and an electron to cleave the dioxygen bond. Other redox reactive amino acids used for catalysis include glycine, cysteine, tyrosine, tryptophan and a similarly modified tyrosine (cross-linked to cysteine).

Cyanide, sulfide, azide and carbon monoxide^[1] all bind to Cytochrome c Oxidase, thus inhibiting the protein from functioning which results in chemical suffocation of cells.

[edit] Additional images

ETC

[edit] References

^ Alonso J, Cardellach F, López S, Casademont J, Miró O (2003). "Carbon monoxide specifically inhibits cytochrome c oxidase of human mitochondrial respiratory chain". Pharmacol Toxicol 93 (3): 142-6. PMID 12969439.