Heme-thiolate proteins

Peroxynitrite reacts with heme proteins such as prostacycline synthase (PGI2), microperoxidase, and the heme thiolate protein P450 to form a ferryl nitrogen dioxide complex as an intermediate [120]. Peroxynitrite also reacts with acetaldehyde with the rate constant of 680 1 mol 1 s" 1 forming a hypothetical adduct, which is decomposed into acetate, formate, and methyl radicals [121]. The oxidation of NADH and NADPH by peroxynitrite most certainly occurs by free radical mechanism [122,123], Kirsch and de Groot [122] concluded that peroxynitrite oxidized NADH by a one-electron transfer mechanism to form NAD and superoxide ... 

This enzyme [EC 1.14.15.3], also known as alkane 1-monooxygenase, lauric acid ca-hydroxylase, fatty acid hydroxylate fatty acids in the [Pg.47]

Mansuy, D. Battioni, P. Diversity of reactions catalyzed by heme-thiolate proteins, The Porphyrin Handbook. Volume 4. Biochemistry and Binding Activation of Small Molecules Eds. Kadish, . M. Smith, . M. Guilard, R. Academic Press San Diego, 2000, pp. 1-15. 

Synthetic active site analogues of heme-thiolate proteins characterization and identification of intermediates of the catalytic cycles of cytochrome P450cam and chloroperoxidase. J. Inorg. Biochem. 83, 289-300. 

Kahn, R.A., S. Bak, C.E. Olsen, I. Svendsen, B.L. MHer (1996). Isolation and reconstitution of the heme-thiolate protein obtusifoliol 14ct-methyl-ase from Sorghum bicolor (L). Moench. J. Biol. Chem. 271, 32944-32950. 

Diversity of Reactions Catalyzed by Heme-Thiolate Proteins Daniel Mansuy... 

Omura T (2005) Heme-thiolate proteins. Biochem Biophys Res Commun 338 404 09... 

Reaction of Heme-thiolate Proteins In their resting states, the P450s and NOSs exist as a mixture of a hexacoor-dinated low-spin state Fe(III) species with a water molecule trans- to one proximal cysteinate ligand and a pentacoordinate high-spin state species with only cysteinate as an axial ligand [248]. The proteins can be reduced to their iron(II) states and transfer electrons to particular substrates as well as bind various ligands such as CO or O2. 

Heme-thiolate proteins have been reported to catalyze a large number of reactions, including diverse types of oxidations, reductions, isomerizations and dehydrations [248]. The nature and mechanism of these reactions have been discussed in detail [248], and the reactions have been shown to be associated with various reactive states under which the heme-thiolate protein can exist. The nature of the iron porphyrin intermediate in the protein that is involved in the activation of a substrate will depend on the reactivity of the substrate. It has recently been shown [253, 254] that in the mutant P450s, the ratio between different reactions that occur on the same substrate wiU be a function of the rates of proton delivery to the active site of P450, suggesting that the presence of distal amino acid residues also affects the rate of transformation of Fe(II)-02 to Fe(III)-00- and Fe(V)=0. 

D. Mansuy, P. Battioni, Diversity of Reactions Catalyzed by Heme-Thiolate Proteins, in The Porphyrin Handbook, (Eds. R. M. Radish, R. M. Smith, R. Guilard), Academic Press, San Diego, 2000, pp. 1-15, Vol. 4. 

Another interesting group of oxidoreductases are the cytochromes P450 (Figure 19). Those heme-thiolate proteins act as monooxygenases and catalyze a wide range of oxidative reactions, such as hydroxylation and epoxidation... 

As shown in Scheme 13.63, tabersonine, in the presence of tabersonine 16-hydroxylase (EC 1.14.13.73), is converted to 16-hydroxytabersonine. The reaction requires both NADPH and oxygen (O2), and NADP and water (H2O) are produced. Tabersonine 16-hydroxylase is a heme-thiolate protein (a P45o).The phenolic hydroxyl group on the aromatic ring undergoes methylation (tabersonine 16-O-methyltransferase, EC 2.1.1.94), while 5-adenosylmethionine is converted to... 

Since their discovery as heme thiolate proteins in the late-1950s, the cytochrome P450s have been recognized as the largest family of enzymes... 

A review has been written on the topic of synthetic active-site analogues of heme-thiolate proteins. As well as cytochrome P450, models for chloro-peroxidase are dicussed. Alkanethiolate-coordinated iron porphyrins and their dioxygen adducts have been synthesized and characterized as P450 models. ... 

Udit AK, Gray HB (2005) Electrochemistry of heme-thiolate proteins. Biochem Biophys Res... 

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