Cytochrome c Oxidase COX

This enzyme present in all animals and plants, aerobic yeast and some bacteria is involved in the next to the last step of oxidative phosphorylation, a process that couples electron transport to ATP synthesis cytochrome c (cytc) delivers electrons to the final component of the respiratory chain, cytochrome c oxidase which reduces O2 to water [39,40]. Crystal structures for both bacterial and mitochondrial multisubunit membrane-boimd COXs are available [41—45]. The enzyme contains two heme groups and three Cu ions. Of these, one heme and one Cu ion (called the heme site) constitute the catalytic center (Fig. 11.5), the remaining 

The heme group is depicted without internal double bonds. 

W is a water molecule. Note the modified tyrosine-histidine couple. 

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The enzyme cytochrome c oxidase ( COX, EC 1.93.1) catalyzes the final step of the respiratory chain. It receives electrons from the small heme protein cytochrome c and transfers them to molecular oxygen, which is thereby reduced to water (see p. 140). At the same time, 2-4 protons per water molecule formed are pumped from the matrix into the intermembrane space. 

The other copper-only binuclear centre to be considered is the CuA or purple copper complex. It is part of the terminal oxidase in mitochondrial respiration, cytochrome c oxidase (COX). Its EPR signature, a seven-line spectrum, has since long been known to be different from the classes type 1 to 3 and arises from two copper ions in a 1.5 valence (or mixed valence) state, first proposed from EPR-analysis of a similar center in nitrous oxide (N20) reductase. There is a close correspondence between the blue and purple states of copper since each of the two copper ions in CuA can be considered as being structurally related to the mononuclear blue site coordination. 

Type 2 centres include superoxide dismutase, discussed above, and cytochrome c oxidase (COX). COX consists of two haem iron centres, cytochrome a and cytochrome a3, and two electronically distinct copper centres, Cua and Cub, which catalyse ... 

The inner membrane of mitochondria is the site of respiratory electron transport and within the inner membrane and the intermembrane space (IMS) of mitochondria are two important copper containing enzymes. First, cytochrome c oxidase (COX) represents the terminal electron acceptor in the respiratory chain and two subunits of this large complex enzyme contain copper sites. A second enzyme in the mitochondria that requires copper is SODl, as described above. Although the vast majority of SODl is cytosolic, a small fraction of this enzyme enters the IMS of the mitochondria where it is believed to directly scavenge superoxide anions produced as a by-product of the electron transport chain. 

Fig. 6. Electron transport in plants and fimgi. Three complexes (7, II and IV) translocate protons to gradient across the mitochondrial membrane Complex 7NADH dehydrogenase complex II succinate dehydrogenase complex III cytochrom be, complex IV cytochrome c oxidase (Cox). Cyc Cytochrome c UbiQ ubiquinone Aox alternative oxidase SHAM salicylhy-droxamic acid AA antimycin A KCN potassimn cyanide. (From Vanlerberghe and McIntosh [137])...

Cytochrome c oxidase (COX) is the terminal enzyme in the respiratory system of most aerobic organisms and catalyzes the four electron transfer from c-type cytochromes to dioxygen (115, 116). The A-type COX enzyme has three different redox-active metal centers A mixed-valence copper pair forming the so-called Cua center, a low-spin heme-a site, and a binuclear center formed by heme-fl3 and Cub. The Cua functions as the primary electron acceptor, from which electrons are transferred via heme-a to the heme-fl3/CuB center, where O2 is reduced to water. In the B-type COX heme-u is replaced by a heme-fo center. The intramolecular electron-transfer reactions are coupled to proton translocation across the membrane in which the enzyme resides (117-123) by a mechanism that is under active investigation (119, 124—126). The resulting electrochemical proton gradient is used by ATP synthase to generate ATP. 

The heme-copper oxidase superfamily is defined hy two criteria (1) a high degree of amino acid sequence similarity within the largest suhunit (suhunit I) and (2) a unique bimetallic active site, consisting of a heme and a closely associated copper atom (see Figure 8), where dioxygen is reduced to water. There are two main branches of the superfamily, which have distinct substrate specificities the mitochondrial respiratory oxidases use cytochrome r as a substrate and, hence, are called cytochrome c oxidases (COX). Bacteria, unlike most mitochondria, contain multiple respiratory oxidases. Many of the prokaryotic respiratory oxidases use membrane-bound quinol (ubiquinol or menaquinol) as a substrate rather than cytochrome c. A number of these quinol oxidases have been shown to be members of the heme-copper oxidase superfamily and to pump protons as efficiently as COXs. " ... 

These include (a) cytochrome c oxidase (COX)-negative muscle fibers [32] and (b) ragged-red fibers [33]. They can be more evident in s-IBM muscle biopsies than in age-matched controls [32], but are not diagnostic. 

Cytochrome c oxidase (COX), cytochrome bd (bd), and cyanide-insensitive oxidase (CIO) operons present in the six complete genomes of Acetobacteriaceae. COX and UOX show another group of gene clusters not homologous to COX and UOX, respectively... 

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