Iron-sulfur units

There is a large body of knowledge on the coordination chemistry of iron-sulfur complexes and iron clusters particularly directed at the modeling and nnderstanding of the action of nonheme proteins whose active sites contain iron-sulfur units. These topics are discussed in detail elsewhere in this Encyclopedia here, the emphasis is on the basic coordination chemistry. 

VJ Fig. 28.14 The iron-sulfur units from ferredoxins, structurally characterized by X-ray diffraction (a) the [2Fe-2S]... 

Fig. 29.15 The iron-sulfur units from ferredoxins, structurally characterized by X-ray diffraction (a) the [2Fe-2S] ferredoxin from spinach (Spinacia oleraced), (b) the [3Fe-4S] ferredoxin from the bacterium Azotobacter vinelandii, and (c) the [4Fe-4S] ferredoxin from the bacterium Chromatium vinosum. Hydrogen atoms are omitted colour code Fe, green S, yellow C, grey.

Many proteins contain a peculiar unit that is made of iron atoms and sulfur (S) atoms. The most widely occurring such unit is a cube in which four iron atoms and four sulfur atoms are occupying alternate positions (see Fig. 6.3). An alternative is a unit that consists of two iron atoms and two sulfur atoms (Fig. 6.3). The proteins that contain such iron-sulfur unit(s) are called iron-sulfur protein. Both of these units act as an electron-transfer unit, by changing its iron between Fe(II) and Fe(ni) as in cytochromes. In particular, iron-sulfur proteins that are involved in photosynthesis are called ferredoxins. Obviously, ferredoxins are not found in humans or other animals they do not perform photosynthesis. However, there are a number of other proteins that contain iron-sulfur units even in human beings. Some of the important iron-sulfur proteins are involved in the electron-transport process in the respiration mentioned above. 

How nitrogenase works is under intensive study by many scientists. Besides, efforts are being made to incorporate a gene of nitrogenase into crop plants, in the hope of eliminating the necessity of artificial nitrogen fertilizer. Anyway, molybdenum is the essential element for this enzyme. In addition, the enzyme uses the iron-sulfur units mentioned earlier. It is thus dependent on iron, sulfur, as well as molybdenum and is one of the most complicated enzymes (see Fig. 21.12 for the entire structure). 

The lUBMB Commission on Nomenclature has issued a number of recommendations dealing with areas of a more biochemical nature (72), such as peptide hormones (86), conformation of polypeptide chains (87), abbreviations for nucleic acids and polynucleotides (88), iron—sulfur proteins (89), enzyme units (90), etc. The Commission has also produced rules and recommendations for naming enzymes (91,92). 

At room temperature, sulfur unites readily with copper, silver, and mercury and vigorously with sodium, potassium, calcium, strontium, and barium to form sulfides. Iron, chromium, tungsten, nickel, and cobalt react much less readily. In a finely divided state, zinc, tin, iron, and aluminum react with sulfur on heating (19). 

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. 

Another feature of mitochondria is that they handle the syntheses of both iron/sulfur and iron haem units. It appears as if handling metal ions, including that of iron, is risky in the cytoplasm. In fact, other metal ions are pumped out of cells or into vesicles and in some cases into mitochondria - especially calcium. 

Bovine heart cytochrome bci (PDB 1BE3 and PDB IBGY) as studied by Iwata et al. exists as a dimer in the asymmetric unit cell. Each monomer consists of 11 different polypeptide subunits (SU) with a total of -2165 amino acid residues and a molecular mass of -240 kDa. The protein subunits of the complex occupy three separate regions (1) the intermembrane space (p side) occupied by cytochrome Ci (subunit 4, SU4), the iron-sulfur protein (ISP, SU5) and subunit 8 (2) the transmembrane region occupied by cytochrome b (SU3), the transmembrane helices of cytochrome Ci and the ISP, and subunits 7,10, and 11 and (3) the matrix space (n side) occupied by two large core proteins (subunits 1 and 2) as well as subunits 6 and 9. Subunit 8 is often called the hinge protein and is thought to be essential for proper complex formation between cytochrome c (the exit point for some bci complex electrons) and... 

A structural unit within iron-sulfur proteins, comprising two or more iron atoms and bridging sulfur atoms (also termed sulfide ligands or sulfido-bridges). These bridging sulfur atoms are acid-labile, generating H2S in the pres-... 

FIGURE 19-11 Cytochrome be, complex (Complex III). The complex is a dimer of identical monomers, each with 11 different subunits. (a) Structure of a monomer. The functional core is three subunits cytochrome b (green) with its two hemes (bH and foL, light red) the Rieske iron-sulfur protein (purple) with its 2Fe-2S centers (yellow) and cytochrome ci (blue) with its heme (red) (PDB ID 1BGY). (b) The dimeric functional unit. Cytochrome c, and the Rieske iron-sulfur protein project from the P surface and can interact with cytochrome c (not part of the functional complex) in the intermembrane space. The complex has two distinct binding sites for ubiquinone, QN and QP, which correspond to the sites of inhibition by two drugs that block oxidative phosphorylation. Antimycin A, which blocks electron flow from heme bH to Q, binds at QN, close to heme bH on the N (matrix) side of the membrane. Myxothiazol, which prevents electron flow from... 

Zuo, J.L., H.C. Zhou, and R.H. Holm. 2003. Vanadium-iron-sulfur clusters containing the cubane-type [VFejSJ core unit Synthesis of a cluster with the topology of the PN cluster of nitrogenase. Inorg. Chem. 42 4624—4631. 

Valuable spectroscopic studies on the dithiolene chelated to Mo in various enzymes have been enhanced by the knowledge of the structure from X-ray diffraction. Plagued by interference of prosthetic groups—heme, flavin, iron-sulfur clusters—the majority of information has been gleaned from the DMSO reductase system. The spectroscopic tools of X-ray absorption spectroscopy (XAS), electronic ultraviolet/visible (UV/vis) spectroscopy, resonance Raman (RR), MCD, and various electron paramagnetic resonance techniques [EPR, electron spin echo envelope modulation (ESEEM), and electron nuclear double resonance (ENDOR)] have been particularly effective probes of the metal site. Of these, only MCD and RR have detected features attributable to the dithiolene unit. Selected results from a variety of studies are presented below, chosen because their focus is the Mo-dithiolene unit and organized according to method rather than to enzyme or type of active site. 

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