Oxygenases, nonheme

FeNO Complexes as Models for Nonheme Oxygenase Enzymes... 

FeNO COMPLEXES AS MODELS FOR NONHEME OXYGENASE ENZYMES... 

Tris(pyrazolyl)borate (Tp) ligands have been employed to model the His3 facial motif in a variety of model complexes of nonheme oxygenase enzymes. Their use is widespread due to the relative ease of modifying the Tp hgand in order to vary steric and electronic effects imparted onto the Fe center. Fiedler and coworkers synthesized several such Fe(Tp)-NO derivatives of the general formula [Fe( Tp)(acac )(NO)] (R substituents defined in Figure 1 acac = substituted acetylacetonate X defined in... 

Keywords Alkyl C-H oxidation Aminopyridine ligands Bioinspired catalysis Hydrogen peroxide Iron coordination complexes Nonheme oxygenases Selectivity... 

The most notable reaction is that of metal-oxygen species with substrate. In the case of heme iron monooxygenases, high-valent iron-oxo species such as 3 or 4 in Fig. 5 are believed to react with substrates. On the other hand, both hydroperoxo (2) and 0x0 (3) are proposed for reactions by nonheme iron oxygenases. There are discussions on whether the iron-oxo species (3) is stabilized in the nonheme oxygenases in the absence of a porphyrin ligand which is effective to form 4. However, the iron-oxo species is attractive for explanation of the results obtained by monooxygenations by nonheme model iron systems. 

In equation 1.16, there are various ligands X /XH that can accept/donate the proton. These include the oxo group in the ferryl active sites in heme and nonheme oxygenase enzymes, the hydroxide at the active site in lipoxygenase, the aniline in equation (1.17), and an imidazolate, as in equation (1.18). As these examples illustrate, some metal-mediated HAT reactions involve a formal separation of the e and H that make up the transferred H . In the case of metal-imidazole complexes the proton and electron are 3 bonds or 4 A separated. Despite this separation, we refer to all of these reactions as HAT. Recent interest into the intimate details of HAT reactions has led to new thinking and new definitions. Still, we prefer the simplest definition of HAT, as reactions where... 

The alkane hydroxylase belongs to a family of nonheme iron oxygenases. There is some structural similarity between the nucleotide sequence of the integral membrane alkane hydroxylase and... 

Rosche B, B Tshisuaka, B Hauer, F Lingens, S Fetzner (1997) 2-Oxo-l,2-dihydroquinoline 8-monooxygen-ase phylogenetic relationship to other multicomponent nonheme iron oxygenases. J Bacterial 179 3549-3554. 

The alkane hydroxylase belongs to a family of nonheme iron oxygenases. There is some structural similarity between the nucleotide sequence of the integral-membrane alkane hydroxylase and the subunits of the monooxygenase encoded by xylA and xylM in the TOL plasmid that are involved in hydrox-ylation of the methyl groups in toluene and xylene in Pseudomonas putida PaWl (Suzuki et al. 1991). 

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... 

These enzymes catalyze a variety of oxidative reactions in natural product biosynthesis with two C—Hhydroxylation examples shown in Figure 13.24 [72,73]. It should be noted thatC—H activation by nonheme iron oxygenases, such as aromatic dioxygenases, is an important pathway in degradation of aromatics into m-dibydrodiols, which are important chiral building blocks for chemical synthesis [74,75]. 

Rosche, B. Tshisuaka, B. Hauer, B., et al., 2-Oxo-l,2-Dihydroquinoline 8-Monooxygenase, Phylogenetic Relationship to other Multicomponent Nonheme Iron Oxygenases. J. Bacteriol, 1997. 179(11) pp. 3549-54. 

Lawrence Que Synthesis of a nonheme ferryl complex, an analogue of nonheme iron oxygenase active intermediates... 

Heme oxygenase is the rate-limiting step in the produetion of CO and its activities account for 86% of endogenous CO produetion the remaining 14% is derived from nonheme sourees. The lifespan of red blood cells is approximately 120 days the older the erythrocyte the greater is its CO output. In neonates, red blood cells have a shorter lifespan and relative to erythrocytes of adults, they produce two to three times more CO (Fallstrom, 1968). HO-2 is activated during neuronal stimulation by phosphorylation by the enzyme CK2 (Boehning et al, 2003). 

Interestingly, even at that time, a series of five histidine residues was postulated to constitute the potential iron-binding site, in that they are also conserved in other lipoxygenases, although site-specific mutagenesis studies indicated that three of these could be mutated individually in 5-LO without loss of either oxygenase or LTA4 synthetase activity (112,113). This proposal has now been refined and it is believed that the nonheme iron is bound permanently by and... 

FIGURE 18.1 Structures of the proposed active oxidants from heme (left) and nonheme (right) iron oxygenases for C=C bond oxidation and the product observed in these reactions. 

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