Iron center

Figure 1.9 Examples of functionally important intrinsic metal atoms in proteins, (a) The di-iron center of the enzyme ribonucleotide reductase. Two iron atoms form a redox center that produces a free radical in a nearby tyrosine side chain. The iron atoms are bridged by a glutamic acid residue and a negatively charged oxygen atom called a p-oxo bridge. The coordination of the iron atoms is completed by histidine, aspartic acid, and glutamic acid side chains as well as water molecules, (b) The catalytically active zinc atom in the enzyme alcohol dehydrogenase. The zinc atom is coordinated to the protein by one histidine and two cysteine side chains. During catalysis zinc binds an alcohol molecule in a suitable position for hydride transfer to the coenzyme moiety, a nicotinamide, [(a) Adapted from P. Nordlund et al., Nature 345 593-598, 1990.)...

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. 

Scheme 10.27 Catalytic cycle of HppE. Dashed arrows indicate electron transport. In this scheme HPP binds to iron1". After a one-electron reduction, dioxygen binds and reoxidizes the iron center. The peroxide radical is capable of stereospecifically abstracting the (pro-R) hydrogen. Another one-electron reduction is required to reduce one peroxide oxygen to water. Epoxide formation is mediated by the resulting ironlv-oxo species.

Another route to enantiomcrically pure iron-acyl complexes depends on a resolution of diastereomeric substituted iron-alkyl complexes16,17. Reaction of enantiomerically pure chloromethyl menthyl ether (6) with the anion of 5 provides the menthyloxymethyl complex 7. Photolysis of 7 in the presence of triphenylphosphane induces migratory insertion of carbon monoxide to provide a racemic mixture of the diastereomeric phosphane-substituted menthyloxymethyl complexes (-)-(/ )-8 and ( + )-( )-8 which are resolved by fractional crystallization. Treatment of either diastereomer (—)-(/J)-8 or ( I )-(.V)-8 with gaseous hydrogen chloride (see also Houben-Weyl, Vol 13/9a, p437) affords the enantiomeric chloromethyl complexes (-)-(R)-9 or (+ )-(S)-9 without epimerization of the iron center. 

The initiating step of the photolysis reaction is the removal of a CO ligand from the metal with generation of a reactive 16e species. The intermediate metal complex is stabilized by an intramolecular oxidative addition of the Si—H bond to the iron center. 

Consider the closely related ion [FeCHiO/e] ". The only difference is in the formal oxidation state of the metal ion. If an ionic model is assumed (9.6), the charge on the metal center is +2. A purely covalent model results in the placing of a formal quadruple negative charge upon the iron center (9.7). To satisfy the electroneutrality principle, and establish a near-zero charge on the metal, each oxygen atom is... 

While crystal structures of rubredoxins have been known since 1970 (for a full review on rubredoxins in the crystalline state, see Ref. (15)), only recently have both crystal and solution structures of Dx been reported (16, 17) (Fig. 3). The protein can be described as a 2-fold symmetric dimer, firmly hydrogen-bonded and folded as an incomplete /3-barrel with the two iron centers placed on opposite poles of the molecule, 16 A apart. Superimposition of Dx and Rd structures reveal that while some structural features are shared between these two proteins, significant differences in the metal environment and water structure exist. They can account for the spectroscopic differences described earlier. 

First isolated from D. desulfuricans (28), desulfoferrodoxin (Dfe) was also isolated from D. vulgaris (29). D is a 28-kDa homodimer that contains two monomeric iron centers per protein. These iron centers were extensively characterized by UV/visible, EPR, resonance Raman, and Mossbauer spectroscopies (30). The data obtained were consistent with the presence of one Dx-like center (center I) and another monomeric iron center with higher coordination number (penta or hexacoordinate), with 0/N ligands and one or two cysteine residues (center II). Comparison of known Dfx sequences led to the conclusion that only five cysteines were conserved, and that only one of them could be a ligand of center II (31). 

Strongly supporting this spectroscopic data, Mossbauer spectroscopy of the as-isolated Rr shows the presence of two types of iron centers a magnetic component that can be well simulated by the parameters of Rd, and a diamagnetic component attributed to the diiron-oxo cluster and resulting from the antiferromagnetic coupling of the two irons. 

The midpoint redox potentials were estimated to be +230 mV (pH = 8.6) or +281 mV (pH = 7.0) for the Rd-like centers, and +339 and +246 mV (pH = 7.0) for the diiron-oxo center 38, 43). This is a surprising observation, since the normal redox potential of Rd centers is about 0 mV. All spectroscopic evidence points to the fact that the monomeric iron centers present in Rr are virtually identical to the ones found in Rd. Hence, it is reasonable to assume that the first coordination sphere of these centers cannot be held responsible for the 250 mV difference in the midpoint redox potentials. 

The proposed mechanism for Fe-catalyzed 1,4-hydroboration is shown in Scheme 28. The FeCl2 is initially reduced by magnesium and then the 1,3-diene coordinates to the iron center (I II). The oxidative addition of the B-D bond of pinacolborane-tfi to II yields the iron hydride complex III. This species III undergoes a migratory insertion of the coordinated 1,3-diene into either the Fe-B bond to produce 7i-allyl hydride complex IV or the Fe-D bond to produce 7i-allyl boryl complex V. The ti-c rearrangement takes place (IV VI, V VII). Subsequently, reductive elimination to give the C-D bond from VI or to give the C-B bond from VII yields the deuterated hydroboration product and reinstalls an intermediate II to complete the catalytic cycle. However, up to date it has not been possible to confirm which pathway is correct. 

Cytochromes. A cytochrome is a protein containing a heme with an iron cation bonded to four donor nitrogen atoms in a square planar array. Figure 20-29a shows the structure of cytochrome c, in which a histidine nitrogen atom and a cysteine sulfur atom occupy the fifth and sixth coordination sites of the octahedral iron center. 

Some early studies [126] on the S-methyldithiocarbazate of 2-formylpyridine, 6, showed it to form low spin iron(III) species, [Fe(6-H)2]C104 and [Fe(6-H)2] [FeCm. The Mossbauer spectrum of the latter showed the presence of two different iron centers, and the compound was a 1 1 electrolyte in nitromethane. 

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