Cytochrome c oxidase structure

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). 

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

Scott, R. A., 1989, X-ray absorption spectroscopic investigations of cytochrome c oxidase structure and function, Ann. Rev. Biophys. Biophys. Chem., 18 137nl58. 

H. Michel, J. Behr, A. Harrenga, and A. Kannt. 1998. Cytochrome c oxidase Structure and spectroscopy Rev. Biophys. Biomol. Struct. 21 329-356. (PubMed)... 

Tsukihara T, Aoyama H, Yamashita E, Tomizaki T, Yamaguchi H, Shinzawaitoh K, Nakashima R, Yaono R and Yoshikawa S 1995 Structures of metai sites of oxidized bovine heart cytochrome c oxidase at 2.8 angstrom Science 269 1069-74... 

Despite considerable efforts very few membrane proteins have yielded crystals that diffract x-rays to high resolution. In fact, only about a dozen such proteins are currently known, among which are porins (which are outer membrane proteins from bacteria), the enzymes cytochrome c oxidase and prostaglandin synthase, and the light-harvesting complexes and photosynthetic reaction centers involved in photosynthesis. In contrast, many other membrane proteins have yielded small crystals that diffract poorly, or not at all, using conventional x-ray sources. However, using the most advanced synchrotron sources (see Chapter 18) it is now possible to determine x-ray structures from protein crystals as small as 20 pm wide which will permit more membrane protein structures to be elucidated. 

Iwata, S., Ostermeier, C., Ludwig, B., Michel, H. Structure at 2.8 A resolution of cytochrome c oxidase from Paracoccus denitrificans. Nature 376 660-669, 1995. 

Tsukihara, T., et al. The whole structure of the 13-subunit oxidized cytochrome c oxidase at 2.8 A resolution. Science 272 1136-1144, 1996. 

FIGURE 21.14 All electrophoresis gel showing the complex subunit structure of bovine heart cytochrome c oxidase. The three largest subunits, I, II, and III, are coded for by mitochondrial DNA. The others are encoded by unclear DNA. (Photo kindly provided by Professor Roderick Capaldi)... 

Chemical structure and reaction mechanisms of cytochrome c oxidase. R. Lemberg, Rev. Pure Appl. Chem., 1965,15,125-136 (132). 

Abramson J, Svensson-Ek M, Byrne B, Iwata S. 2001. Structure of cytochrome c oxidase A comparison of the bacterial and mitochondrial enzymes. Biochim Biophys Acta 1544 1. 

Ostermeier C, Harrenga A, Ermler U, Michel H. 1997. Structure at 2.7 A resolution of the Paracoccus denitrificans two-subunit cytochrome c oxidase complexed with an antibody Ev fragment. Proc Natl Acad Sci USA 94 10547. 

Recently, hf structure associated with the copper signal of cytochrome c oxidase has been reported by Frondsz et al.210 which used octave bandwidth S-band EPR spectroscopy (2-4 GHz). The observed structure has been attributed to copper hfs and to an additional magnetic interaction. Data obtained from powder simulation of the EPR spectra at 2.62 GHz and 3.78 GHz are collected in Table 12.2. In a subsequent paper Frondsz and Hyde211 have shown that in S-band EPR spectra of copper complexes in frozen solutions, improved spectral resolution can be achieved. This new technique, which allows a proper selection of the microwave frequency between 2 and 4 GHz, is therefore recommended for studying powder EPR spectra of these types of compounds. 

Another type of inhibitor combines with the enzyme at a site which is often different from the substrate-binding site and as a result will inhibit the formation of the product by the breakdown of the normal enzyme-substrate complex. Such non-competitive inhibition is not reversed by the addition of excess substrate and generally the inhibitor shows no structural similarity to the substrate. Kinetic studies reveal a reduced value for the maximum activity of the enzyme but an unaltered value for the Michaelis constant (Figure 8.7). There are many examples of non-competitive inhibitors, many of which are regarded as poisons because of the crucial role of the inhibited enzyme. Cyanide ions, for instance, inhibit any enzyme in which either an iron or copper ion is part of the active site or prosthetic group, e.g. cytochrome c oxidase (EC 1.9.3.1). 

Figure 4 Structural details of the active site heme a3-CuB of cytochrome c oxidase...

Doxombicin binds readily to ceU membranes, changing their structure and function. The targets of doxombicin binding are compounds with a negative charge, of which the most extensively studied is the phospholipid cardiolipin (Pollakis et ah, 1983). Cardiolipin occurs in high concentrations in the inner mitochondrial membrane, where it is required for full activity of cytochrome c oxidase. In a recent study (Das and Mazumdar, 2000), the interaction between cytochrome c oxidase and cardiohpin in the presence of doxombicin was analysed, and the results of pico-second time-resolved fluorescence depolarization showed that the cardiohpin layer was depleted due to complexation with the dmg. 

Das, T.K. and Mazumdar, S., 2000, Effect of Adriamycin on the boundary hpid structure of cytochrome c oxidase pico-second time-resolved fluorescence depolarization studies. Biophys. Chem. 86 15-28... 

Figure 7.39 Schematic diagram for cytochrome c oxidase. Distances taken from bovine heart X-ray crystallographic structure (PDB 20CC). Entry and exit channels for dioxygen, protons, and water are schematic only. (Adapted with permission from Figure 1 of reference 138. Copyright 2004 American Chemical Society.)...

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