Editing Cytochrome c oxidase (section)

=== The complex ===
The complex is a large [[integral membrane protein]] composed of several [[Cofactor (biochemistry)#Metal ions|metal prosthetic sites]] and 13<ref name="pmid22902835">{{cite journal |vauthors=Kadenbach B, Huttemann M |date=September 2015 |title=The subunit composition and function of mammalian cytochrome c oxidase |url=https://pubmed.ncbi.nlm.nih.gov/26190566/ |journal=Mitochondrion |volume=24 |issue= |pages=64-76 |doi=10.1016/j.mito.2015.07.002 |pmid=26190566 |doi-access=free}}</ref> protein subunits in mammals. In mammals, ten subunits are nuclear in origin, and three are synthesized in the mitochondria. The complex contains two [[heme]]s, a [[cytochrome a]] and [[cytochrome a|cytochrome a{{sub|3}}]], and two copper centers, the Cu{{sub|A}} and Cu{{sub|B}} centers.<ref name="pmid7652554">{{cite journal | vauthors = Tsukihara T, Aoyama H, Yamashita E, Tomizaki T, Yamaguchi H, Shinzawa-Itoh K, Nakashima R, Yaono R, Yoshikawa S | title = Structures of metal sites of oxidized bovine heart cytochrome c oxidase at 2.8 A | journal = Science | volume = 269 | issue = 5227 | pages = 1069–74 | date = August 1995 | pmid = 7652554 | doi = 10.1126/science.7652554 | bibcode = 1995Sci...269.1069T | s2cid = 27210776 }}</ref> In fact, the cytochrome a{{sub|3}} and Cu{{sub|B}} form a binuclear center that is the site of oxygen reduction. [[Cytochrome c]], which is reduced by the preceding component of the respiratory chain (cytochrome bc1 complex, Complex III), docks near the Cu{{sub|A}} binuclear center and passes an electron to it, being oxidized back to cytochrome c containing Fe{{sup|3+}}. The reduced Cu{{sub|A}} binuclear center now passes an electron on to cytochrome a, which in turn passes an electron on to the cytochrome a{{sub|3}}>-Cu{{sub|B}} binuclear center. The two metal ions in this binuclear center are 4.5 Å apart and coordinate a [[hydroxide ion]] in the fully oxidized state.

[[X-ray crystallography|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). It plays a vital role in enabling the cytochrome a{{sub|3}}- Cu{{sub|B}} binuclear center to accept four electrons in reducing molecular oxygen and four protons to water. The mechanism of reduction was formerly thought to involve a [[peroxide]] intermediate, which was believed to lead to [[superoxide]] production. However, the currently accepted mechanism involves a rapid four-electron reduction involving immediate oxygen{{ndash}}oxygen bond cleavage, avoiding any intermediate likely to form superoxide.<ref name = "Voest_2011" />{{rp|865–866}}