Horseradish peroxidase axial ligand

Kumar D, de Visser SP, Sharma PK et al (2005) The intrinsic axial ligand effect on propene oxidation by horseradish peroxidase versus cytochrome P450 enzymes. J Biol Inorg Chem 10 181-189... 

The spectrum of CIII japanese radish peroxidase exhibits two widely splitted lines with a quadrupole splitting AEq = 2.37 mm s 1 and an isomer shift 8pe = 0.29 mm s 1 at 77°K [145], very similar to those observed in oxyhemoglobin [144], a horseradish peroxidase [146], The electronic structure of the iron is apparently determined by the Fe-C>2 bond with a marginal contribution of the fifth, axial ligand provided by the protein (Fig. 11.8). 

Unlike the case of optical or MCD spectroscopy, the presence of a nearby free radical (porphyrin or amino acid) has only a small effect on the Mossbauer spectra of ferryl iron (by contrast the nature of the axial ligand appears to have a greater effect on the Mossbauer spectra). Thus in the absence of a magnetic field there is little difference between the Mossbauer spectra of horseradish peroxidase compounds I and II [134,181,183]. Due to... 

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. 

Horseradish peroxidase, which is the most fully characterized of the heme(Fe )-centered enzymes for the activation of HOOH, has an axial histidine ligand this also is the case for myeloperoxidase (uses HOOH and CF to form HOCl). In contrast, the catalase protein (catalyzes the harmless destruction of HOOH into O2 and H2O) has an axial tyrosine ligand in place of the histidine... 

X-ray crystal structures have been determined for beef-liver catalase and for horseradish peroxidase in the resting, high-spin ferric state. In both, there is a single heme b group at the active site. In catalase, the axial ligands are a... 

Figure 17 A schematic view of the involvement of axial ligands and distal residues in the push-pull mechanism for 0-0 bond cleavage of an iron-bound peroxide in thiolate-ligated (left) and histidine-ligated (right) systems such as cytochrome P450 and horseradish peroxidase, respectively ...

Horseradish peroxidase is one of a class of heme enzymes (also including chloroperoxidase, vide supra) that catalyze the overall two electron oxidation of organic substrates with H2O2 as the oxidant or electron acceptor (Eq. 3) [50]. Unlike P-450 and chloroperoxidase, the axial fifth ligand to the heme iron of horseradish peroxidase is a nitrogen donor (histidine). 

The absorption spectrum of the Compound I form of chloroperoxidase is different from that of horseradish peroxidase Compound I, and is more closely analogous to that of catalase Compound I. This suggests that it may also have a Aiu ground state [22, 50]. However, the EPR spectrum of chloroperoxidase Compound I indicates that there is electron density at the meso carbons this finding is inconsistent with a Ai ground electronic state [50, 93]. Thus, the different absorption spectral properties of the Compound I intermediates of peroxidases may not derive solely from differences in orbital symmetry. Rather, other factors such as the nature of the axial ligand or the macrocycle stereochemistry may be responsible for these spectral differences. 

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