Methionine residues cytochrome

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. 

Chen et al. [47] demonstrated that the reaction of HOC1 with cytochrome c increased cytochrome peroxidase activity by the oxidation of the methionine residue. Methionine oxidation also significantly decreased the efficiency of cytochrome c as a mitochondrial electron carrier. HOC1, HOBr, and HOI are also able to oxidize (Fen)cytochrome c [48],... 

The two differently bound methionine sulphur in the b and c-type haem proteins encouraged measurements of the respective S 2p binding energy value. In myoglobin, a representative of the b-type proteins, the methionine residue is exclusively located in the polypeptide side chain with no direct metal sulphur bonding. By way of contrast cytochrome c has one methionine coordinated to iron. 

Cytochrome c has 4 methionine residues, two of which are covalently linked to the haem moiety One of the other two methionine residues is coordinated to the iron in the axial position The major S 2 p band of the crystalline compound appears at 162.6 eV attributable to the methionine residues. Prolongued irradiation causes an increase of the RSOJ or the sulphate band from 28% to 40% (Table 2). When aqueous cytochrome c is recorded, the amount of oxidised sulphur rises to 63% of the methionine sulphur band. The possible extraneously bound redox active transition metals, probably, have created a metal driven Haber Weiss reaction which led to the marked amount of oxidised sulphur observed. Splitting of the iron-sulphur bonding by cyanide results in dramatic increase of the 167.7 band and the additional appearance of a S 2p signal at 164.3, probably due to RS=0 species. This oxidation is believed to be catalyzed by the haem iron. Hydrogen peroxide alone converts the methionine sulphur completly to sulphonic acid. 

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... 

Methemoglobin reductase, cytochrome bt reductase and, 164-165 Methionine residues glyceraldehyde-3-phosphate dehydrogenase, 11... 

Fig. 19.3 (a) Schematic view of cylodirome c. The heme group is viewed edge on, with the iron atom (large black atom) coordinated to a sulfur atom from a methionine residue and a nitrogen atom from a histidine residue, (b) Stereoview of the cytochrome c molecule. Each number represents an amino acid in Ihe protein chain. Note the complete coordination sphere of the iron atom as well as the protection afforded by the encircling protein chains. (Courtesy of R. R. Dickerson and from Takano, T. Trus, B. I.. Mandel, N. Mandel, G. Kallai, O. B. Swanson. R. Dickerson. R. E. J. liiol. Chetn. 1977, 252, 776-785. Reproduced with permission.)... 

All our attempts to observe Pt NMR signals from either PtCli " or cis-Pt( NH3)aCl2 bound to reduced cytochrome c or ribo-nuclease A (RNase) have so far failed. These platinum complexes are known to bind to the sulphur atoms of exposed methionines (residues 65 and 29 of Cyt c and RNase respectively) as shown by our previous H NMR studies on RNase (28) and those of Boswell et al on Cyt c (29) and x-ray crystallography. We assume therefore that the resonances are broadened beyond detection via chemical shift anisotropy relaxation. The restriction of Pt mobility on the protein will lead to a large increase in (see CSA equation above). The anisotropy term would also be expected to increase. Scalar coupling to N will also contribute to the increase in linewidths if nitrogen binding sites are involved. 

The reduction of ferricytochrome c by hydrated electrons and by several free radicals has been studied by pulse radiolysis. The reduction of oxidized cytochrome c by [Fe(edta)] - follows first-order kinetics for both protein and reductant, with a rate constant of 2.57 x 10 1 mol" s" at pH 7 and activation enthalpy and entropy of 6.0 kcal mol" and —18 cal K" mol", respectively. These values are comparable to those for outer-sphere cytochrome c reductions and redox reactions involving simple iron complexes, and are compatible with outer-sphere attack of [Fe(edta)] " at the exposed haem edge, although the possibility of adjacent attack through the haem pocket is not ruled out. The rate data at pH 9 are consistent with [Fe(edta)] " reduction of two slowly interconverting forms of the protein, native kt = 2.05 X10 1 mol" S" ) and high-pH kt = 2.67 x 10 1 mol" s" ) isomers. A possible route for the transfer of the electron from Cr + to ferricytochrome c has been suggested as a result of the chemical analysis of the chromium(m) product. The reduction by Cr + of the native protein and of ferricytochrome c carboxy-methylated at the haem-linked methionine (residue 80) has been studied kinetically. At pH 6.5 the former process is simple and corresponds to a second-order rate constant of 1.21 x 10 1 mol" s". The latter, however, is complex - two chromium-... 

Therefore, we investigated a molecular interaction of cardiolipin with cytochrome c. As shown in Figure 2, cytochrome c consists of 5 helices and inter-helical loops which harbor a heme c prosthehc group by covalent thioether-bonds through cysteine-14 and -17 residues. Ferric ion, centered in the pyrrole ring, is axially liganded by histidine-18 and methionine-80 residue. The lower half of the protein consishng of flexible random coils is a rather soft stmcture and has a space between the heme c plate and P-loops inside the smah basic protein. 

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