Iron-tyrosinate complex

Ribonucleotide reductases are discussed in Chapter 16. Some are iron-tyrosinate enzymes while others depend upon vitamin B12, and reduction is at the nucleoside triphosphate level. Mammalian ribonucleotide reductase, which may be similar to that of E. coli, is regarded as an appropriate target for anticancer drugs. The enzyme is regulated by a complex set of feedback mechanisms, which apparently ensure that DNA precursors are synthesized only in amounts needed for DNA synthesis.273 Because an excess of one deoxyribonucleotide can inhibit reduction of all... 

The visible spectra of the intradiol dioxygenases (Fig. 2) are characterized by a broad absorption band centered near 460 nm with molar extinction coefficients of 3000-4000 M-1 cm-1 16>34). The color disappears upon reduction of the ferric ion with dithionite and is regenerated upon exposure of the solution to oxygen. Resonance Raman studies on these enzymes15 35-38) have been reported by several laboratories (Table 4). These spectra are characterized by a set of four peaks at ca. 1605, 1505, 1270, and 1175 cm-1, which are assigned to ring vibrations of Fe(III) coordinated tyrosinate ligands. Similar spectra are obtained for the transferrins as well as for model iron-phenolate complexes (Table 4). A new class of iron proteins seems to... 

Table 4. Resonance Raman frequencies of phenolate ring vibrations in iron-tyrosinate proteins and model complexes...

LjPt(CF3)X complexes (with L = tetraaryldiphosphines and X = CH CIj, OH, OPh) are hydroxylation catalysts of phenol and phenol ethers, with 70% HjO [46]. In all cases, high ortho-selectivity (up to 95%) is observed. Phenylalanine is hydroxylated by a water-soluble iron porphyrin complex to tyrosine and dihydroxy phenylalanine (DOPA) in good yields [47]. Other hydroxylation catalysts of various aromatic substrates are halogenated porphyrin complexes of Fe and Mn [48-49],... 

Reaction mechanism Based on the observation of reaction intermediates in the crystal structure and on quantum chemical calculations Einsle et al. [148] propose an outline of the first detailed reaction mechanism of the cytochrome c Nir from W. succinogenes. Nitrite reduction starts with a het-erolytic cleavage of the weak N-O bond, which is facilitated by a pronounced backbonding interaction between nitrite and the reduced active site iron. The protons come firom a highly conserved histidine and tyrosine. Elimination of one of both amino acids results in a significant reduced activity. Subsequently, two rapid one-electron reductions lead to a FeNO form and, by protonation, to a HNO adduct. A further two-electron two-proton step leads to hydroxylamine. The iron in the hydroxylamine complex is in the Fe(III) state [149], which is unusual compared to synthetic iron-hydroxylamine complexes where the iron is mainly in the Fe(II) state. Finally, it readily loses water to give the product, ammonia. This presumably dissociates firom the Fe(III) form of the active site, whose re-reduction closes the reaction cycle. 

Similarly, the oxidation of Fe " during iron core formation in recombinant human H subunit ferritin and its variants has been investigated by stopped-ftow kinetics and Mossbauer spectroscopy [494]. An intermediate species, attributed to the purple Fe -Tyr34 complex in the Fe2 site, was shown to form rapidly ( ox 1000 s ) and to decay within the first 5-10 s. This Fe -tyrosinate complex was shown to form following the rapid uptake and oxidation of Fe, and was proposed as one of the initial steps in the fast mineralization process [474]. The oxidation of Fe has been shown to lead to the formation of various species, including Fe " " monomers, dimers, and some larger clusters. Specifically, the observed fast oxida-... 

In hemoglobin M, histidine F8 (His F8) has been replaced by tyrosine. The iron of HbM forms a tight ionic complex with the phenolate anion of tyrosine that stabilizes the Fc3 form. In a-chain hemoglobin M variants, the R-T equilibrium favors the T state. Oxygen affinity is reduced, and the Bohr effect is absent. P Ghain hemoglobin M variants exhibit R-T switching, and the Bohr effect is therefore present. 

The enzyme catalyzing the formation of retinal 2 by means of central cleavage of P-carotene 1 has been known to exist in many tissues for quite some time. Only recently, however, the active protein was identified in chicken intestinal mucosa (3) following an improvement of a novel isolation and purification protocol and was cloned in Escherichia coli and BHK cells (4,5). Iron was identified as the only metal ion associated with the (overexpressed) protein in a 1 1 stoichiometry and since a chromophore is absent in the protein heme coordination and/or iron complexation by tyrosine can be excluded. The structure of the catalytic center remains to be elucidated by X-ray crystallography but from the information available it was predicted that the active site contains a mononuclear iron complex presumably consisting of histidine residues. This suggestion has been confirmed by... 

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