Iron-sulfur cluster structure

One of the first methods used for investigating the iron-sulfur-cluster structure was reported by Cammack and Evans for FeS-A/FeS-B in photosystem I. The thylakoid polypeptides were unfolded in a 80% dimethyl sulfoxide solution containing guanidine-HCl and the EPR line shapes ofboth FeS-A and FeS-B were consistent with the [4Fe 4S] type. As FeS-X was not yet known at that time, its cluster structure was not taken into consideration. 

Nonrepetitive but well-defined structures of this type form many important features of enzyme active sites. In some cases, a particular arrangement of coil structure providing a specific type of functional site recurs in several functionally related proteins. The peptide loop that binds iron-sulfur clusters in both ferredoxin and high potential iron protein is one example. Another is the central loop portion of the E—F hand structure that binds a calcium ion in several calcium-binding proteins, including calmodulin, carp parvalbumin, troponin C, and the intestinal calcium-binding protein. This loop, shown in Figure 6.26, connects two short a-helices. The calcium ion nestles into the pocket formed by this structure. 

Inspection of the citrate structure shows a total of four chemically equivalent hydrogens, but only one of these—the pro-/J H atom of the pro-i arm of citrate—is abstracted by aeonitase, which is quite stereospecific. Formation of the double bond of aconitate following proton abstraction requires departure of hydroxide ion from the C-3 position. Hydroxide is a relatively poor leaving group, and its departure is facilitated in the aeonitase reaction by coordination with an iron atom in an iron-sulfur cluster. 

Plus 241 distance constraints for the unassigned residues close to the iron—sulfur cluster derived from the X-ray structure... 

Resonance Raman studies of the recombinant proteins showed vibrational bands at the 200-430 cm region characteristic of iron-sulfur clusters (124). Most interestingly, on Fe and O isotope sensitive band was detected at 801 cm which could be attributed to either a Fe(IV)=0 species or a monobridged Fe-O-Fe structure. This observation, together with Mossbauer analysis, which indicated a mixed N, 0, and S ligand environment for cluster 2, suggests a Fe-O-Fe or Fe=0 unit as part of the structure for cluster 2. 

Fig. 8. The structure of D. gigas hydrogenase showing the novel heterodinuclear [NiFe] site, the three iron-sulfur clusters, and the tracing of the polypeptide chain...

EPR studies on electron transfer systems where neighboring centers are coupled by spin-spin interactions can yield useful data for analyzing the electron transfer kinetics. In the framework of the Condon approximation, the electron transfer rate constant predicted by electron transfer theories can be expressed as the product of an electronic factor Tab by a nuclear factor that depends explicitly on temperature (258). On the one hand, since iron-sulfur clusters are spatially extended redox centers, the electronic factor strongly depends on how the various sites of the cluster are affected by the variation in the electronic structure between the oxidized and reduced forms. Theoret-... 

Trinuclear Cuboidal and Heterometallic Cubane-Type Iron-Sulfur Clusters New Structural and Reacticity Themes in Chemistry and Biology R. H. Holm... 

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... 

Fig. 5.4(a). Structures of iron-sulfur clusters found in proteins, (b) An hydrogenase active site. Note the presence of CO and CN ligands, which could have been present in the primitive anaerobic environment. 

If one applies the same procedure to Figure 1.10B, an iron-sulfur cluster often used as a model for those in biological systems, the same magic number of 60 would be obtained. Cluster magic numbers would occur as 48 e for a triangular clusters, 60 e for tetrahedral, 72 e for trigonal bipyramidal, 74 e for square pyramidal, 86 e for octahedral, 90 e for trigonal prisms, and 120 e for cubic structures. 

To successfully describe the structure and function of nitrogenase, it is important to understand the behavior of the metal-sulfur clusters that are a vital part of this complex enzyme. Metal-sulfur clusters are many, varied, and usually involved in redox processes carried out by the protein in which they constitute prosthetic centers. They may be characterized by the number of iron ions in the prosthetic center that is, rubredoxin (Rd) contains one Fe ion, ferredoxins (Fd) contain two or four Fe ions, and aconitase contains three Fe ions.7 In reference 18, Lippard and Berg present a more detailed description of iron-sulfur clusters only the [Fe4S4] cluster typical of that found in nitrogenase s Fe-protein is discussed in some detail here. The P-cluster and M center of MoFe-protein, which are more complex metal-sulfur complexes, are discussed in Sections 6.5.2. and 6.5.3. 

For updating the information presented in this chapter, a literature search on the keyword nitrogenase modified with structure, X ray, Mossbauer, iron sulfur cluster, or model compound will generate citations referring to the newest research results. A search of the Protein Data Bank (PDB) at the website address http //www.rcsb.org/pdb/ will yield the latest updates on X ray, NMR, and other submitted structural data. 

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