Iron-sulfur proteins cubane structure

One of the essential cofactor enzymes in the cytochrome P450 network provides electrons to reduce iron and or oxygen to generate the active oxidant. These natural electron-transfer materials are typified by the iron-sulfur proteins(16). Work by Holm and others has modeled the basic iron-sulfur cores of these proteins and a variety of structure types have been modeled. One of these types, an iron-sulfur cubane like cluster consists of interpenetrating tetrahedra of iron and sulfide ions. 

Fig. 5.2. Schematic representation of cubane-like structures found in 4-Fe sites in iron-sulfur proteins...

Iron Sulfur Compounds. Many molecular compounds (18—20) are known in which iron is tetrahedrally coordinated by a combination of thiolate and sulfide donors. Of the 10 or more structurally characterized classes of Fe—S compounds, the four shown in Figure 1 are known to occur in proteins. The mononuclear iron site REPLACE occurs in the one-iron bacterial electron-transfer protein rubredoxin. The [2Fe—2S] (10) and [4Fe—4S] (12) cubane structures are found in the 2-, 4-, and 8-iron ferredoxins, which are also electron-transfer proteins. The [3Fe—4S] voided cubane structure (11) has been found in some ferredoxins and in the inactive form of aconitase, the enzyme which catalyzes the stereospecific hydration—rehydration of citrate to isocitrate in the Krebs cycle. In addition, enzymes are known that contain either other types of iron sulfur clusters or iron sulfur clusters that include other metals. Examples include nitrogenase, which reduces N2 to NH3 at a MoFe S8 homocitrate cluster carbon monoxide dehydrogenase, which assembles acetyl-coenzyme A (acetyl-CoA) at a FeNiS site and hydrogenases, which catalyze the reversible reduction of protons to hydrogen gas. 

The Fe protein (also called nifH after the gene that encodes it) is the vehicle for a 4Fe/4S cubane-type cluster (Figure 2), in which the tetrahedral coordination at each iron atom is completed by a cysteine residue. The Fe protein is a homodimer, and the cluster lies at the interface between the two units, held by Cys97 and Cysl32 from each subunit. The X-ray crystal structure of the Fe protein shows that the iron-sulfur cluster is exposed to solvent, a feature that presumably assists in acquisition of electrons from its natural electron donors (flavodoxin or ferredoxin). ... 

The [3Fe-4S] core present in D.gigas Fd II can be interconverted into a cubane structure [4Fe-4S]. This fadie conversion occur upon incubation of the protein with an excess of Fe in the presence of a reducing agent (e.g. dithiothreitol). A summary of the interconversion pathways as well as the potentialities of the method for specific labelling an iron-sulfur core was previously discussed (26,49). Combination of Fe isotopic enrichment and specific introduction of a forth iron atom into the [3Fe-4S] core produces different isotopic labelled clusters. 

MSssbauer studies of Fd n have established that the protein contains a 3-Fe cluster, and that the three iron sites reside in a predominantly tetrahedral environment of sulfur ligands. The cluster has a Fe3S4 stoichiometry (see Beinert and Thomson (17)), and EXAFS data (14) suggest a compact core with an Fe-Fe distance of 2.7 A, just as observed for Fe4 cubanes. The structure is perhaps close to that shown on the left of Figure 1. Thus, we picture the Fe3S4 cluster as a cubane Fc4S4 cluster from which one Fe has been removed. This view is supported by the observation... 

Each P-cluster is actually a joined pair of cubane-type clusters, one Fe4S4 and one Fe4S3 with two bridging cysteine -SH groups and one iron atom bonded to three sulfide sulfur atoms (Fig. 24-3).17/23 The FeMo-coenzyme can be released from the MoFe-protein by acid denaturation followed by extraction with dimethylformamide.24 While homocitrate was identified as a component of the isolated coenzyme, the three-dimensional structure of FeMo-co was deduced from X-ray crystallography of the intact molybdenum-iron protein.14/17/18... 

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