Cytochrome oxidases structure

Another important outcome of the structural analysis is the relative positioning of the metal sites and their distances in order to define plausible electron transfer pathways between electron donors and acceptors. A common pattern starts to emerge (the same applies to cytochrome oxidase (241, 242). Figure 11 gives a pictorial view of the electron transfer pathway ... 

Proteins involved in the fundamental structure and function of neurons are decreased in schizophrenia. Several postmortem studies have identified consistent reductions in the expression of mitochondrial associated genes involved in oxidative metabolism, such as cytochrome oxidase and cytochrome C reductase [23], Reduced oxidative metabolism is consistent with evidence of increased brain lactate,... 

Cytochrome c can easily be extracted from tissue particles by dilute salt solutions. It was isolated by Keilin and Hartree in 1930 and shown to contain a porphyrin ring structure. In 1933 Zeilen and Reuter established that cytochrome c was a heme (iron-porphyrin) protein. Slightly different forms of cytochrome a were distinguished in yeast and bacteria by Keilin in 1934 and the different properties of cytochrome a and a3 by Tamiya et al. in 1937. The identity of cytochrome 03, the enzyme which activates oxygen with Warburg s atmungsferment, was proposed by Keilin in 1939. Cytochrome a/a3 was renamed cytochrome oxidase by Malcolm Dixon (1939). The oxidation route then offered was ... 

More recently, Yoshikawa,Tsukihara, and co-workers published a study of fully oxidized (PDB 1V54) and fully reduced (PDB 1V55) bovine heart cytochrome c oxidase structures. " In this study, they identified an aspartate residue, asp51, which undergoes a substantial change in position between the oxidized and reduced structures (see inset in Figure 7.41A). 

C. (1979). A re-evaluation of some basic structural and functional properties of Pseudomonas cytochrome oxidase. Biochem. ]. 183, 701-709. 

Michel, H., Behr, J., Harrenga, A., Kannt, A. (1998) Cytochrome c oxidase structure and spectroscopy. Annu. Rev. Biophys. Biomol. Struct. 27, 329-356. 

The CuA center has an unusual structure.130-132 It was thought to be a single atom of copper until the three-dimensional structure revealed a dimetal center, whose structure follows. The CuB-cytochrome a3 center is also unusual. A histidine ring is covalently attached to tyrosine.133-1353 Like the tyrosine in the active site of galactose oxidase (Figs. 16-29,16-30), which carries a covalently joined cysteine, that of cytochrome oxidase may be a site of tyrosyl radical formation.135... 

Cytochrome oxidase also serves as a proton pump, so that the process of electron transfer is associated with the vectorial transfer of protons across the membrane, and thus contributes to the establishment of the proton gradient which is used to drive the synthesis of ATP. Cytochrome oxidase is located in the inner mitochondrial membrane of animal, plant and yeast cells (the eukaryotes) and in the cell membrane of prokaryotes. The arrangement is represented schematically in Figure 58. The complexity of cytochrome oxidase and the problems associated with its solubilization from the membrane have presented great obstacles to the elucidation of the structure and mechanism of the enzyme, but its importance has resulted in an enormous literature, which has been reviewed frequently.1296 1299... 

Bacterial cytochrome oxidases offer an interesting area of study that complements well that of mitochondrial cytochrome oxidase. In some cases they are readily solubilized from the membrane they tend to have fewer subunits than the mitochondrial oxidase and they form stable intermediates during the reaction with dioxygen. They often do not have a role in energy transduction, a fact reflected in their simpler structures. 

The arrangement of the metal centers is in remarkable agreement with the structure, also reported in 1995 [49b], for another member of the superfamily of heme-copper oxidases, the cytochrome oxidase from Paracoccus denitrificans. The two structures show a strikingly similar coordination and arrangement of the five redox-active metals (the two irons and three coppers). 

M19. Miiller-Hocker, J., Johannes, A., Droste, M., Kadenbach, B., Pongratz, D., and Hubner, G., Fatal mitochondrial myopathy in Kearns-Sayre syndrome with deficiency of cytochrome oxidase in the cardiac and skeletal muscle An enzyme-histochemical ultra-immunocytochemical fine structural study in longterm frozen autopsy tissue. Virchows Arch. B Cell Pathol. Incl. Mol. Pathol. 52, 353-367 (1986). 

It has long been established that the functional unit of cytochrome oxidase contains four redox-active metal centres. Two of these, cytochromes a and a3, contain heme A (Fig. 5-23) coordinated in different ways in subunit I. The heme group is not covalently linked to the protein. The main structural features are the carbonyl group at position 8 and the isoprenoid chain at position 2 of the porphyrin ring. 

Structural information about cytochrome oxidase is very limited beyond the level of primary structure as it has proved impossible to grow crystals of sufficiently high quality for high resolution X-ray studies. Cytochrome oxidase is a transmembrane protein which is inserted asymmetrically through the membrane. The overall shape is like a Y, with the stalk extending about 50 A above the membrane plane on the... 

---