Cysteine thiolate peroxidase

Ferryl complexes have been implicated in the reaction mechanisms of peroxidases and cytochromes P450. 38,1596 Pqj. horseradish peroxidase, two intermediates are spectroscopically detectable. Compound I, formed upon addition of peroxide to the resting Fe form of the enzyme, is a green species that is formally two oxidation levels higher than the resting state, and is widely believed to consist of an (Fe =0) + unit complexed by a porphyrin jt-cation radical. The [(P" ) Fe =0]+ complexes are discussed in Section 9. Compound II, which is red, and is obtained upon one-electron reduction of Compound I, also possesses a (Fe =0) + unit, in this case complexed by a normal porphyrin dianion, PFe =0. The fifth ligand, provided by the protein in the various enzymes, is a cysteine thiolate for the cytochromes nitric oxide synthases... 

Axial ligands of heme-containing enzymes, such as a cysteine thiolate in cytochromes P450 and chloroperoxidases, a histidine imidazole in peroxidases, and a tyrosine phenolate in catalases, are... 

Fig. 1 Reactions involving molecular oxygen and its reduced congeners in heme proteins. Reactions where equilibria are manifest are indicated as such. In globins, peroxidases, cytochrome oxidases, and heme oxygenases, the axial ligand X is a protein-derived histidine in catalases, X is a tyrosine phenolate in chloroperoxidases and cytochromes P450, X is a cysteine thiolate...

TPP = tetraphenylporphine CP = chloroperoxidase HRP = horseradish peroxidase - the 5th ligand is probably cysteine thiolate Mb = myoglobin CAM = camphor... 

Cytochrome P-450, which is the most extensively studied of the monooxygenase proteins, has a heme-iron active center with an axial thiol ligand (a cysteine residue). However, most chemical model investigations use simple iron(III) porphyrins without thiolate ligands. As a result, model mechanisms for cytochrome P-450 invoke a reactive intermediate that is formulated to be equivalent to Compound I of horseradish peroxidase, (por+-)Fe =0, with a high-potential porphyrin cation radical. Such a species would be reduced by thiolate, and therefore is an unreasonable formulation for the reactive center of cytochrome P-450. 

P450 chloroperoxidase contains a thiolate group of a cysteine side chain as the fifth iron ligand. Chloroperoxidase forms compounds 1 and 11, as do other peroxidases. A chloride ion may combine with compound 1 to form a complex of hypochlorite with the Fe(lll) heme. 

NADH peroxidase is structurally homologous to GR. The charge-transfer thiolate in GR is structurally equivalent to the redox active cysteine in NADH peroxidase however, no interchange thiol is present in NADH peroxidase. The reactivity of the equivalent active site cysteines with H2O2 is drastically different, with the cysteine in NADH peroxidase reacting much faster than that in... 

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