Structure, cytochromes

Black SD, Coon MJ. P-450 cytochromes structure and function. Adv Enzymol 60 35-75, 1987. 

This procedure was designed to work with any cytochrome structure and, for example, can be applied to humans, bacteria, fish and plant cytochromes. There are more than 120 P450 families, and more than 1000 P450 eri2 ymes. All these structures can in theory be imported, processed and used for the prediction of the site of metabolism. The procedure is totally automatic, does not require any user assistance, and only requires the availability of the 3D structure of the enzyme. 

Barker PD, Ferguson SJ. Still a puzzle why is haem covalently attached in c-type cytochromes Structure 1999 7 R281-R290. 

Fig. 16.5, Phylogenetic trees derived on the basis of distance metrics derived from differences in various local structural parameters at topologically equivalent positions in a family of homologous cytochrome structures...

T. Groves, Y.Z. Han, P.R. Montellano, Cytochrome Structure, Mechanism and Biochemistry, Plenum Press, New York, 1995 (Chapter 1). 

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... 

Figure 3.7 The polypeptide chains of cytochrome bs62 and human growth hormone both form four-helix-bundle structures.

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. 

The L and the M subunits are firmly anchored in the membrane, each by five hydrophobic transmembrane a helices (yellow and red, respectively, in Figure 12.14). The structures of the L and M subunits are quite similar as expected from their sequence similarity they differ only in some of the loop regions. These loops, which connect the membrane-spanning helices, form rather flat hydrophilic regions on either side of the membrane to provide interaction areas with the H subunit (green in Figure 12.14) on the cytoplasmic side and with the cytochrome (blue in Figure 12.14) on the periplasmic side. The H subunit, in addition, has one transmembrane a helix at the car-boxy terminus of its polypeptide chain. The carboxy end of this chain is therefore on the same side of the membrane as the cytochrome. In total, eleven transmembrane a helices attach the L, M, and H subunits to the membrane. 

No region of the cytochrome penetrates the membrane nevertheless, the cytochrome subunit is an integral part of this reaction center complex, held through protein-protein interactions similar to those in soluble globular multisubunit proteins. The protein-protein interactions that bind cytochrome in the reaction center of Rhodopseudomonas viridis are strong enough to survive the purification procedure. However, when the reaction center of Rhodohacter sphaeroides is isolated, the cytochrome is lost, even though the structures of the L, M, and H subunits are very similar in the two species. 

Figure 12.14 The three-dimensional structure of a photosynthetic reaction center of a purple bacterium was the first high-resolution structure to be obtained from a membrane-bound protein. The molecule contains four subunits L, M, H, and a cytochrome. Subunits L and M bind the photosynthetic pigments, and the cytochrome binds four heme groups. The L (yellow) and the M (red) subunits each have five transmembrane a helices A-E. The H subunit (green) has one such transmembrane helix, AH, and the cytochrome (blue) has none. Approximate membrane boundaries are shown. The photosynthetic pigments and the heme groups appear in black. (Adapted from L. Stryer, Biochemistry, 3rd ed. New York ...

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. 

Actual and predicted structures of an (X-helical domain of cytochrome bgg2... 

Cytochromes were first named and classified on the basis of their absorption spectra (Figure 21.9), which depend upon the structure and environment of their heme groups. The b cytochromes contain iron—protoporphyrin IX (Figure 21.10), the same heme found in hemoglobin and myoglobin. The c cytochromes contain heme c, derived from iron-protoporphyrin IX by the covalent attachment of cysteine residues from the associated protein. UQ-cyt c... 

FIGURE 21.11 The structure of UQ-cyt c reductase, also known as the cytochrome hci complex. The alpha helices of cytochrome b (pale green) define the transmembrane domain of the protein. The bottom of the structure as shown extends approximately 75 A into the mitochondrial matrix, and die top of the structure as shown extends about 38 A into the intermembrane space. (Photograph kindly provided by Di Xia and Johann Deismhofer [From Xia, D., Yn, C.-A., Kim, H., Xia,J-Z., Kachnrin, A. M., Zhang, L., Yn,... 

The structure of the UQ-cyt c reductase, also known as the cytochrome bc complex, has been determined by Johann Deisenhofer and his colleagues. (Deisenhofer was a co-recipient of the Nobel Prize in Chemistry for his work on the structure of a photosynthetic reaction center [see Chapter 22]). The complex is a dimer, with each monomer consisting of 11 protein subunits and 2165 amino acid residues (monomer mass, 248 kD). The dimeric structure is pear-shaped and consists of a large domain that extends 75 A into the mito-... 

FIGURE 21.13 The structure of mitochou-dtial cytochrome c. The heme is shown at the center of the structure, covalently linked to the protein via its two sulfur atoms (yellow). A third sulfur from a methionine residue coordinates the iron. 

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)... 

Cramer, W. A., et al., 1996. Some new structural aspects and old controversies concerning die cytochrome b /complex of oxygenic photosyndie-... 

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