Coordination environment of the iron

Electrochemical experiments allow the determination of complex stability constants for Fe2+ by measuring complex redox potentials over a range of pH values. The Fe34YFe2+ redox potential of the siderophore complex, as with the spectral characteristics of the complex, is dependent on the inner coordination environment of the iron. These considerations will be addressed later (Section III.D). 

Figure 12-6 Structure of Fe(DTPA)2- found in the salt Na2[Fe(DTPA)] - 2H20. The seven-coordinate pentagonal bipyramidal coordination environment of the iron atom features three N and two O ligands in the equatorial plane (dashed lines) and two axial O ligands. The axial Fe-O bond lengths are 11 to 19 pm shorter than those of the more crowded equatorial Fe-O bonds. One carboxyl group of the ligand is uncoordinated. [D. C. Flnnen, A. A. Pinkerton, W. R. Dunham, R. H. Sands, and M. O. Funk. Jr..

The transferrins belong to the iron-tyrosinate group of proteins discussed in Section 62.1.5.5.2. Charge transfer from phenolate ligands to Fem accounts for the salmon-pink colour of transferrin. The detailed coordination environment of the iron in transferrin is not known with certainty, as... 

The pH dependence of cytochrome c oxidation-reduction reactions and the studies of modified cytochrome c thus demonstrate that the coordination environment of the iron and the conformation of the protein are relatively labile and strongly influence the reactivity of the metallo-protein toward oxidation and reduction. The effects seen may originate chiefly from alterations in the thermodynamic barriers to electron transfer, but the conformation changes are expected to affect the intrinsic barriers also. One such conformation change is the opening of the heme crevice referred to above. The anation and Cr(II) reduction studies provide an estimate of 60 sec 1 for this process in Hh(III) at 25°C (59). To date, no evidence has been found for a rapid heme-crevice opening step in ferrocytochrome c. 

Several important points have emerged from the structural analyses performed on single crystals of ferritins. The identification of the ferroxidase centers is one, the similarities and differences between ferritins from different parts of the same organism another, and the differences between, for example, mammalian and bacterioferritins a third. Another relevant consideration is the fact that very little is really known about the iron sites in vivo, especially the construction of the core. Most of what has been suggested about the coordination environments of the iron centers has been inferred from a combination of mutagenesis studies, comparison with better-characterized systems, e.g., diiron protein sites to compare with the ferroxidase center or iron oxyhydroxide minerals for the core, and some model compound studies. 

Figure 3 The suggested coordination environments of the iron centres in ferritin ferroxidase sites for (a) bacterioferritin reduced form, 2 x Fe(II) (b) bacterioferritin oxidized form, 2 x Fe(III) (c) human ferritin (Fl-chain) both oxidized and reduced forms (d) E. coli ferritin (ecFTN) oxidized and reduced forms and...

The H64 distal ligand of wild-type myoglobin does not coordinate to the heme iron in either the reduced or the oxidized form of the native protein but stabilizes the coordination of a distally boimd water molecule of metMb. Replacement of H64 with other amino acid residues can, therefore, change the coordination environment of the heme iron in two ways. Such variants either may possess a distal residue that is able to coordinate to the heme iron or may possess a distal residue that is incapable of either coordinating to the iron or of forming a hydrogen bond with a coordinated water molecule. 

Myoglobin is a protein of molecular weight of about 17,000 with the protein chain containing 153 amino acid residues folded about the single heme group. This restricts access to the iron atom (by a second heme) and reduces the likelihood of formation of a hematin-like Fe(III) dimer. The micro environment is similar to that in Cytochrome c, but there is no sixth ligand (methionine) to complete the coordination sphere of the iron atom. Thus there is a site to which a dioxygen molecule may reversibly bind. 

In crystalline oxides and hydroxides of iron (III) octahedral coordination is much more common than tetrahedral 43). Only in y-FegOs is a substantial fraction of the iron (1/3) in tetrahedral sites. The polymer isolated from nitrate solution is the first example of a ferric oxyhydroxide in which apparently all of the irons are tetrahedrally coordinated. From the oxyhydroxide core of ferritin, Harrison et al. 44) have interpreted X-ray and electron diffraction results in terms of a crystalline model involving close packed oxygen layers with iron randomly distributed among the eight tetrahedral and four octahedral sites in the unit cell. In view of the close similarity in Mdssbauer parameters between ferritin and the synthetic poljmier it would appear unlikely that the local environment of the iron could be very different in the two materials, whatever the degree of crystallinity. Further study of this question is needed. 

Chloroprotohemin in pyridine solution shows a different behavior two quadrupole fine pairs replace the single quadrupole fine pair for chloroprotohemin in aqueous solution. The wide quadrupole splitting (1.8 mm/S) of the new line pair is more characteristic of Mossbauer spectra obtained for methemoglobin these spectra will be discussed in the next section, but it suffices to point out here that the pyridine coordination produces an environment more nearly like the hexacoordinated environment of the iron in the hemoproteins (78). 

Despite the limited information about the coordination environment of the metal center, a mechanism for the a-keto acid-dependent enzymes has been proposed (Figure 27) [222] in which the a-keto acid binds to the iron center and primes it for 02 binding. Attack of the bound 02 on the coordinated a-keto acid at the C-2 position results in decarboxylation of the a-keto acid to give an Fe(II)-peroxy derivative that can react with substrate either directly or via a high-valent iron-oxo intermediate to give the oxygenated substrate, a carboxylic acid, and the starting Fe(II) enzyme. 

Several enzymes with peroxidase-like action have also been used in immunoassays. Microperoxidases are catalytically active fragments obtained from cytochrome c by proteolytic action. They consist of the heme group covalently coupled to a short peptide alpha helix (26). The active site structure is similar to that of peroxidase Four of the six possible coordination bonds of the iron atom are occupied by bonding to the porphyrin while the fifth complexes with a histidine residue and the sixth is exposed to the environment and forms the catalytically active portion of the molecule. The reaction mechanism and spectrum of substrates is similar to HRP, although the specific activity is variable... 

NRVS represents the ultimate limit in vibrational selectivity, because it reveals the vibrational spectrum of an individual probe atom even when embedded in a complex environment such as a biomolecule containing thousands of other atoms. Fe NRVS is thus an exquisite probe for the structure and dynamics of the immediate coordination sphere of the iron, which is the heart of the reactivity of numerous important proteins. 

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