7-Iron ferredoxin models

Noodleman, L., 8c Baerends, E. J. (1984). Electronic structure, magnetic properties, ESR, and optical spectra for 2-iron ferredoxin models by LCAO-Xa valence bond theory. Journal of the American Chemical Society, 106, 2316. 

Activation of an M-CO bond for nucleophilic substitution in anion radical metallo-complexes appears to be quite a general effect (Kaim 1987 Mao et al. 1989,1992 Shut et al. 1995 Klein et al. 1996). Such activation seems to be the basis of metal-cluster catalytic activity. The iron-sulfur cluster (Bu4N)2Fe4S4(SPh)4 deserves to be mentioned here. The cluster is considered as a ferredoxin model (Inoue Nagata 1986) it catalyzes an electron transfer from //-butyl lithium or phenyl lithium to 5-phenyl thiobenzoate or phenylbenzoate (Inoue Nagata 1986). 

A wide variety of synthetic binuclear iron complexes (39) bridged by sulfide, disulfide and/or thiolate groups are known. They have proven to be good models for the two-iron ferredoxin proteins, as demonstrated by comparisons of structure and properties. Early attempts to isolate two-iron complexes by direct reaction of a monothiol with FeCl3, NaSH and NaOMe afforded only four-iron products suggesting that a particularly high stability is associated with the tetrameric... 

The iron-sulphur centre is probably of the 2Fe-2S type [191,223]. It is a one-electron donor/acceptor with of approx. 280 mV in mitochondria (pH independent below pH 8 [224,225]). It exhibits an EPR spectrum in the reduced state that is somewhat anomalous for 2Fe-2S clusters (see Ref. 221). This, as well as the high midpoint redox potential, suggest that the iron ligands may be less electronegative than the four cysteine sulphurs of the plant ferredoxin model (see Ref. 226). The EPR spectrum of the FeS cluster is affected by the redox state of ubiquinone... 

The initial 6 A-resolution X-ray work showed one of the [4Fe 4S] clusters is 15 A and the other 22 A from the preceding iron-sulfur electron acceptor, FeS-X. Discussion of the iron-sulfur center FeS-X itself will be deferred to Chapter 31, where the interaction of the FeS-X domain with PsaC (FeS-A/FeS-B) and its involvement in electron transfer to FeS-A/B will also be addressed. More recent work by the Berlin group at 4 A resolution has refined the distance measurements to 15.4 and 22.2 A, respectively. Fig. 12 (B) shows a three-dimensional model of PsaC based on low-temperature EPR measurements by Kamlowski and coworkers on PS-I single crystals. Their interpretation was made by using the bacterial ferredoxin model as a PsaC substitute in the PS-I reaction center matrix, and adjusting its orientation for the best agreement with the EPR data. The g-tensor orientation of EeS-A and FeS-B in the PS-I single crystals determines the PsaC orientation relative to the two clusters. 

Recently Jensen and co-workers have determined the structure of a clostridial-type ferredoxin obtained from Micrococcus aerogenes (47). One of the two apparently identical iron-sulfur clusters is illustrated in Fig. 2. The structure is compatible with a model with iron and labile sulfide at alternate comers of a cube. This accounts for the equivalence of these moieties in the protein. Another 8-iron-8 labile sulfur ferredoxin, from Clostridium acidiurici, similarly contains two independent iron-sulfur clusters per molecule (48). Strahs and Kraut (49) had earlier discovered... 

Oxidized Fe2S2 ferredoxins, containing two equivalent iron atoms, with J = 400 cm , show sharper NMR lines with respect to the monomeric iron model provided by oxidized rubredoxin (107-109), due to the decreased Boltzmann population of the paramagnetic excited states. For reduced ferredoxins (Si = 5/2, S2 = 2), with J = 200 cm , the ground state is paramagnetic (S = 1/2) (110). A smaller decrease in linewidth is expected. However, the fast electron relaxation rates of the iron(II) ion cause both ions to relax faster, and the linewidths in the dimer are sharp. 

The multinuclear tetrahedral iron clusters have the potential for additional formal oxidation states. Because not all of these states have been found in proteins or model compounds, it is possible that some oxidation states may be unstable. For a given Fe S protein only one redox couple is used the other possible states appear to be excluded by restrictions of the protein structure. This selection rule is illustrated with two 4Fe 4S low-molecular-weight electron transfer proteins ferredoxin and high-potential iron protein (HiPIP). The 4Fe 4S clusters in both proteins were shown by X-ray crystallography to be virtually identical. However, the redox potential and oxidation states for the two proteins are vastly... 

A brief historical note on the structure of the iron-sulfur clusters in ferredoxins is relevant. After the first analytical results revealed the presence of (nearly) equimolar iron and acid-labile sulfur, it was clear that the metal center in ferredoxins did not resemble any previously characterized cofactor type. The early proposals for the Fe S center structure were based on a linear chain of iron atoms coordinated by bridging cysteines and inorganic sulfur (Blomstrom et al., 1964 Rabino-witz, 1971). While the later crystallographic analyses of HiPIP, PaFd, and model compounds (Herskovitz et al., 1972) demonstrated the cubane-type structure of the 4Fe 4S cluster, the original proposals have turned out to be somewhat prophetic. Linear chains of sulfide-linked irons are observed in 2Fe 2S ferredoxins and in the high-pH form of aconitase. Cysteines linked to several metal atoms are present in metallothionein. The chemistry of iron-sulfur clusters is rich and varied, and undoubtedly many other surprises await in the future. 

Several models have been proposed for the active center of iron and sulphur in Clostridial ferredoxin in which the cysteine residues in the peptide chain participate in the sulphur bridging. Fig 9 166). Unfortunately X-ray analysis of crystals of these proteins has not been completed. It is difficult to confirm that all the irons are clustered in a single linear array 167, 168). X-ray studies of another non-heme iron protein, the high potential iron protein, hipip, from chromatium, carried out by J. Kraut (personal communication), indicate that the four irons of this molecule may be clustered in a tetrahedral array. 

Meanwhile, Blumberg and Peisach (145) showed that the interaction between a low-spin ferrous atom and an adjacent free radical can give rise to a g= 1.94 EPR signal. Brintzinger, Palmer, and Sands (146) proposed the first two-iron model for the active center of a plant-type ferredoxin. Their model, which consisted of two spin-coupled, low-spin ferric atoms in the oxidized protein and one low-spin ferric and one low-spin ferrous atom in the reduced protein, explained much of the chemical data on the proteins. Later, they (Brintzinger, Palmer, and Sands, (147)) presented EPR data for a compound, bis-hexamethylbenzene, Fe(I), which demonstrated all the properties fo the g= 1.94 signal observed in the ferredoxins. 

Several Mossbauer spectroscopic papers have dealt with members of the plant-type ferredoxins. In these papers, the Mossbauer spectra for a particular protein were interpreted to yield information such as the oxidation state and spin state of the iron atoms in the protein, and in some cases this information was extended to validate a proposed model for the active site. However, problems with denatured protein material or incorrect interpretation of the Mossbauer data have prevented any of these models from being accepted as valid. 

In addition, the two-iron Schiff s base compounds studied by Lewis et al. (160—162) have magnetic properties which indicate a structure which may be similar to that in the active centers of the plant-type ferredoxins. The following arguments set forth criteria on which to base any model for the active site ... 

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