Cysteine residues cytochromes

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... 

There are two types of electron transport those involving flavoproteins and iron-sulfur proteins, and those requiring only flavoproteins. The X-ray crystal structure of the soluble cytochrome P450 from Pseudomonas putida grown on camphor (P-450-CAM) has been determined (Poulos et ah, 1985), as have several others. The haem group is deeply embedded in the hydrophobic interior of the protein, and the identity of the proximal haem iron ligand, based on earlier spectroscopic studies (Mason et ah, 1965) is confirmed as a specific cysteine residue. 

Cytochromes are electron-transfer proteins having one or several haem groups. Cytochrome c binds to the protein by one or, more commonly two, thioether bonds involving sulphydryl groups of cysteine residues. The fifth haem iron ligand is always provided by a histidine residue. Cytochrome c has been proved to be a useful model system for studying the relationship between protein structure and thermostability due to the availability of its three-dimensional structure from a wide variety of organisms, both mesophiles and thermophiles. 

Heme coenzymes (8) with redox functions exist in the respiratory chain (see p. 140), in photosynthesis (see p. 128), and in monooxygenases and peroxidases (see p. 24). Heme-containing proteins with redox functions are also referred to as cytochromes. In cytochromes, in contrast to hemoglobin and myoglobin, the iron changes its valence (usually between +2 and +3). There are several classes of heme (a, b, and c), which have different types of substituent - Ri to - R 3. Hemoglobin, myoglobin, and the heme enzymes contain heme b. Two types of heme a are found in cytochrome c oxidase (see p. 132), while heme c mainly occurs in cytochrome c, where it is covalently bound with cysteine residues of the protein part via thioester bonds. 

Metal ion chelates of various porphyrins, differing in their substituents at positions 1-8, are intimately involved in a great number of life processes. Iron protoporphyrin (13) is the most common form and serves as the cofactor of a large number of enzymes. Usually (13) is non-covalently bound to its conjugate apoenzymes. Examples of covalently attached (13) are provided by c-type cytochromes, the attachment being between two vinyl side chains of (13) and two cysteine residues of the protein. Other biologically important derivatives of porphyrin include chlorophyll a (14), bacteriochlorophyll a and heme a (B-79MI11002). 

Iron protoporphyrin IX (heme) is found in the b-type cytochromes and in hemoglobin and myoglobin. In heme c, cysteine residues of the protein (R) are attached covalently by thioether links to the two vinyl (—CH=CH2) groups of protoporphyrin IX. Heme c is found in the c cytochromes. In heme A, which is found in the a cytochromes, a 15-carbon isoprenoid side chain is attached to one of the vinyls, and a formyl group replaces one of the methyls. 

Some small peptide-heme complexes have been prepared, including an undecapeptide (residues 11-21)668"669 and an octapeptide (residues 14-21). TTiese are useful models as they include the two cysteine residues that covalently link the heme to the peptide, and one of the axial ligands. The axial Met-80 residue is absent, but the position can be filled by methionine or by other ligands as required.670 Work with several octapeptide complexes shows that the rates of outer-sphere electron transfer appear to be independent of the axial ligand, and faster than the reaction for cytochrome c. Other comparisons show that the orientation of the axial methionine in cytochrome c and the contacts between heme and protein are important controlling factors in the electronic structure of the heme. Aqua and hydroxo complexes of iron(III) octapeptide complexes are also useful models for studying spin equilibria in iron(III) hemoproteins.671... 

Several diverse metal centres are involved in the catalysis of monooxygenation or hydroxylation reactions. The most important of these is cytochrome P-450, a hemoprotein with a cysteine residue as an axial ligand. Tyrosinase involves a coupled binuclear copper site, while dopamine jS-hydroxylase is also a copper protein but probably involves four binuclear copper sites, which are different from the tyrosinase sites. Putidamonooxin involves an iron-sulfur protein and a non-heme iron. In all cases a peroxo complex appears to be the active species. 

Figure 16 The heme ring of cytochrome c is a non-amino acid, prosthetic group bound to the protein through two cysteine residues.

Hackett, C.S., Novoa, W.B., Ozols, J. Strittmatter, P. (1986). Identification of the essential cysteine residue of NADH-cytochrome b5 reductase. Journal of Biological Chemistry 261, 9854-7. 

Shirabe, K., Yubisui, T., Nishino, T. Takeshita, M. (1991). Role of cysteine residues in human NADH-cytochrome b5 reductase studied by site-directed mutagenesis. Journal of Biological Chemistry 266, 7531-6. 

Sulfur (S) Sulfur is a yellow solid. Iron-sulfur clusters are found in cytochrome enzymes. The sulfur-containing amino acid cysteine is common in hair. Cysteine residues can connect to each other via disulfide bridges, giving hair a natural curl. Permanent waves are achieved by artificially removing and then re-forming these disulfide bridges. 

---