Nonheme iron center

This impressive reaction is catalyzed by stearoyl-CoA desaturase, a 53-kD enzyme containing a nonheme iron center. NADH and oxygen (Og) are required, as are two other proteins cytochrome 65 reductase (a 43-kD flavo-protein) and cytochrome 65 (16.7 kD). All three proteins are associated with the endoplasmic reticulum membrane. Cytochrome reductase transfers a pair of electrons from NADH through FAD to cytochrome (Figure 25.14). Oxidation of reduced cytochrome be, is coupled to reduction of nonheme Fe to Fe in the desaturase. The Fe accepts a pair of electrons (one at a time in a cycle) from cytochrome b and creates a cis double bond at the 9,10-posi-tion of the stearoyl-CoA substrate. Og is the terminal electron acceptor in this fatty acyl desaturation cycle. Note that two water molecules are made, which means that four electrons are transferred overall. Two of these come through the reaction sequence from NADH, and two come from the fatty acyl substrate that is being dehydrogenated. 

The enzymatic reactions of peroxidases and oxygenases involve a two-electron oxidation of iron(III) and the formation of highly reactive [Fe O] " species with a formal oxidation state of +V. Direct (spectroscopic) evidence of the formation of a genuine iron(V) compound is elusive because of the short life times of the reactive intermediates [173, 174]. These species have been safely inferred from enzymatic considerations as the active oxidants for several oxidation reactions catalyzed by nonheme iron centers with innocent, that is, redox-inactive, ligands [175]. This conclusion is different from those known for heme peroxidases and oxygenases... 

Rbo is a homodimeric protein, each subunit of which contains two distinct mononuclear nonheme iron centers in separate domains (Fig. 10.4) (Coehlo et al. 1997). Center I contains a distorted rubredoxin-type [Fe(SCys)4] coordination sphere. [Fe(SCys)4] sites in proteins are known to catalyze exclusively electron transfer, which is, therefore, the putative function for center I. Center II contains a unique [Fe(NHis)4(SCys)] site that is rapidly oxidized by 0, and is, therefore, the likely site of superoxide reduction (Lombard et al. 2000). A blue nonheme iron protein, neelaredoxin (Nlr) from Desulfovibrio gigas (Silva et al. 1999), contains an iron center closely resembling that of Rbo center II (Table 10.1). The blue color is due to the oxidized (i.e., Fe(III)) form [Fe(NHis)4(SCys)] site, which, in both Nlr and Rbo, has a prominent absorption feature at -650 nm. Reduction of center II to its Fe(II) form fully bleaches its visible absorption. These absorption features have been used to probe the reactivity of Rbo with superoxidie. 

Cyclic voltammetry has been also used for estimation of the rate constants for oxidation of water-soluble ferrocenes in the presence of HRP (131). There is a perfect match between the data obtained spectrophotometrically and electrochemically (Table IV), which proves that the cyclic voltammetry reveals information on the oxidation of ferrocenes by Compound II. It is interesting to note that an enzyme similar to HRP, viz. cytochrome c peroxidase, which catalyzes the reduction of H202 to water using two equivalents of ferrocytochrome c (133-136), is ca. 100 times more reactive than HRP (131,137). The second-order rate constant equals 1.4 x 106 M-1 s 1 for HOOCFc at pH 6.5 (131). There is no such rate difference in oxidation of [Fe(CN)e]4- by cytochrome c peroxidase and HRP (8). These comparisons should not however create an impression that the enzymatic oxidation of ferrocenes is always fast. The active-R2 subunit of Escherichia coli ribonucleotide reductase, which has dinuclear nonheme iron center in the active site, oxidizes ferrocene carboxylic acid and other water-soluble ferrocenes with a rate constant of... 

Nagashima S, Nakasako M, Dohmae N, et al. Novel nonheme iron center of nitrile hydratase with a claw setting of oxygen atoms. Nature Struct Biol 1998 5 347-52. 

Ye S, Neese F. Quantum chemical studies of C-H activation reactions by high-valent nonheme iron centers. Curr Opin Chem Biol. 2009 13 89-98. 

Biological systems overcome the inherent unreactive character of 02 by means of metalloproteins (enzymes) that activate dioxygen for selective reaction with organic substrates. For example, the cytochrome P-450 proteins (thiolated protoporphyrin IX catalytic centers) facihtate the epoxidation of alkenes, the demethylation of Al-methylamines (via formation of formaldehyde), the oxidative cleavage of a-diols to aldehydes and ketones, and the monooxygenation of aliphatic and aromatic hydrocarbons (RH) (equation 104). The methane monooxygenase proteins (MMO, dinuclear nonheme iron centers) catalyze similar oxygenation of saturated hydrocarbons (equation 105). ... 

The ferriheme protein metmyoglobin (metMb) at the physiological pH 7.4 was reported to bind the NO molecule reversibly yielding the nitrosyl adduct [metMb(NO)] the kinetics of the association and dissociation processes were investigated and a limiting dissociation mechanism was proposed (58,68). 2-His-l-Glu nonheme iron center engineered into myoglobin was reported capable to bind Fe(II) and reduce NO to N2O (69). 

Structural data on the organization of the active clusters and the various subunits can be obtained from biochemical, biophysical and genetic studies. However, the final word is in the mouth of the crystallographer, after the biochemist hands him the crystals. Only one piece of solid information is available to date, and this is the amino acid sequences of subunits la and Ib [78,79]. These two subunits should accommodate the P-700, the primary electron acceptor (Ai), and probably the secondary electron acceptor A2 which is the nonheme iron cluster X. The amino acid sequences of subunits I and I, make it unlikely that these subunits also contain one of the bound ferredoxins A or B because subunit I, contains 4 cysteine residues and subunit I, contains only 2 cysteines [79]. These numbers are hardly sufficient for the formation of the nonheme iron cluster X which is supposed to be a nonheme iron center [74,88]. Therefore, it may be likely that sub-... 

M. Lubben, A. Meetsma, E. C. Wilkinson, B. Feringa, L. Que Jr., Nonheme iron centers in oxygen activation Characterization of an iron(III) hydroperoxide intermediate, Angew. Chem. Int. Ed. Engl. 34 (1995) 1512. 

The methane mono-oxygenase proteins (MMO, binuclear nonheme iron centers) catalyze similar oxygenation of saturated hydrocarbons - ... 

It has been isolated as a two-subunit protein, but genetic evidence suggests the presence of additional subunits. The small subunit is a cytochrome c, while the larger subunit is predicted to bind two protohemes as well as a nonheme iron center. This protein also shows sequence homology with cytochrome c oxidase. It contains no copper, but it has been suggested that a heme l)-nonheme Fe center similar to the heme fl-Cug center of cytochrome c oxidase may be presenf. If may be fhe site af which fhe nifrogen atoms of two molecules of NO are joined to form A differenf kind of... 

Arene dioxygenases, or Rieske dioxygenases (RDO), are enzymes that contain both a mononuclear, nonheme iron center as well as a Rieske-type, Fe2S2 cluster. They have a wide-ranging... 

We have explored the reactivity of Fe(TPA) complexes with peroxides and found that such centers are capable of activating peroxides to functionalize alkanes in a catalytic fashion. Because of the efficient stoichiometric transfer of coordinated halide onto the alkane substrate, we have been able to deduce the participation of an [(TPA)Fe(X)=0] + species in these reactions. Finally the high valent intermediate can be stabilized under appropriate conditions to allow its spectroscopic characterization. These experiments provide significant insight into how nonheme iron centers may function in enzyme active sites for the functionalization of unactivated C-H bonds. 

Que. L.J. Oxygen Activation at Nonheme iron Centers. In Active Oxygen in Biochemisny Valentine. J.S.. Foote. C.S.. Greenberg. A.. Liebman. J.F.. Eds. Blackie Academic Professional London. 1995 Vol. 3. 232-275. 

Each of the proposed mechanisms begins first by the coupling of two NO molecules in the active site containing the two different iron centers (a heme iron center and a nonheme iron center) leading to the initial formation of a hyponitrite intermediate complex. The manner in which the diiron centers couple with the two NO molecules to form the hyponitrite complex, and how this affects the breaking of the N—O, has been a question of serious experimental and theoretical scrutiny. The N—O bond of the hyponitrite complex is proposed to be one of the bonds that breaks during NO reduction leading to the release of N2O and H2O. 

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