Other iron-sulfur clusters

Figure 8.3 Outline reaction cycle of NiFe hydrogenase.The minimal hydrogenase is depicted, consisting of the [NiFe] centre in the large subunit, and the proximal [4Fe-4S] cluster (C) in the small subunit.The reaction is written in the direction of the oxidation of H2. Electrons are transferred out through the other iron-sulfur clusters to an acceptor protein (not shown).The equivalent states of the NiFe centre B, SR, R and C are indicated. Reduced centres are shaded. Electron transfers are accompanied by transfers of hydrons (not shown).

Ferredoxin is an electronic trump card. Sitting at the top of this list, it can easily push electrons onto carbon chains, other iron-sulfur clusters, CO, or nitrogen. The biological electron box NADH is also near the top of the Ust. This is the molecule that your body uses to supply electrons, so it has considerable electron-pushing power itself... 

Iron Sulfur Compounds. Many molecular compounds (18—20) are known in which iron is tetrahedraHy coordinated by a combination of thiolate and sulfide donors. Of the 10 or more stmcturaHy 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 mbredoxin. The [2Fe—2S] (10) and [4Fe—4S] (12) cubane stmctures are found in the 2-, 4-, and 8-iron ferredoxins, which are also electron-transfer proteins. The [3Fe—4S] voided cubane stmcture (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 NH at a MoFe Sg 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. 

In summary, it appears that the protein has to adopt the correct fold before the Rieske cluster can be inserted. The correct folding will depend on the stability of the protein the Rieske protein from the thermoacidophilic archaebacterium Sulfolobus seems to be more stable than Rieske proteins from other bacteria so that the Rieske cluster can be inserted into the soluble form of the protein during expression with the help of the chaperonins. If the protein cannot adopt the correct fold, the result will be either no cluster or a distorted iron sulfur cluster, perhaps using the two cysteines that form the disulfide bridge in correctly assembled Rieske proteins. 

It has always been assumed that these simple proteins act as electron-transfer proteins. This is also a fair conclusion if we take in account that different proteins were isolated in which the Fe(RS)4 center is in association with other non-heme, non-iron-sulfur centers. In these proteins the Fe(RS)4 center may serve as electron donor/ac-ceptor to the catalytic site, as in other iron-sulfur proteins where [2Fe-2S], [3Fe-4S], and [4Fe-4S] clusters are proposed to be involved in the intramolecular electron transfer pathway (see the following examples). 

Iron-sulfur clusters, such as those discussed in Chapter 6, cannot be treated using the 16-e or 18-e rules. Other frameworks exist to treat large metal clusters, and these have some utility in treating [Fe4S4]n+ clusters. One method treats the... 

Chapter 6). Other iron-sulfur proteins, so named because they contain iron sulfur clusters of various sizes, include the rubredoxins and ferredoxins. Rubredoxins are found in anaerobic bacteria and contain iron ligated to four cysteine sulfurs. Ferredoxins are found in plant chloroplasts and mammalian tissue and contain spin-coupled [2Fe-2S] clusters. Cytochromes comprise several large classes of electron transfer metalloproteins widespread in nature. At least four cytochromes are involved in the mitrochondrial electron transfer chain, which reduces oxygen to water according to equation 1.29. Further discussion of these proteins can be found in Chapters 6 and 7 of reference 13. 

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. 

There are many other proteins that contain iron in a form that is neither in haem nor in iron-sulfur clusters. We have already encountered the iron storage and transport proteins, ferritin and transferrin (see Chapter 8). We propose to discuss here two other classes of iron-containing proteins, those with mononuclear non-haem iron centres and those with dinuclear non-haem iron centres. 

Iron-sulfur proteins are a group of enzymes and other electron carriers that contain clusters of iron and sulfide linked directly to amino-acyl side chains, usually cysteines. They are widely distributed in nature. Soon after their discovery. Hall et al. (1971) proposed that they could be used to follow the course of evolution. Studies of genome sequences have revealed that iron-sulfur cluster binding motifs are among the most commonly recognized sequences. 

In this text, iron-sulfur clusters are discussed because they appear in proteins and enzymes (1) cytochrome b(6)f, Rieske [2Fe-2S] cluster (Section 7.5 and Figure 7.26) (2) cytochrome bci, Rieske [2Fe-2S] cluster (Section 7.6 and Figure 7.30) and (3) aconitase, [4Fe-4S] cluster (Section 7.9.2.1, and Figure 7.50). The iron-sulfur protein (ISP) component of the cytochrome b(6)f and cytochrome bci complexes, now called the Rieske ISP, was first discovered and isolated by John S. Rieske and co-workers in 1964 (in the cytochrome bci complex). More information about the RISP is found in Section 7.5.1. Section 7.9.2 briefly discusses other proteins with iron-sulfur clusters—rubredoxins, ferrodoxins, and the enzyme nitrogenase. The nitrogenase enzyme was the subject of Chapter 6 in the hrst edition of this text— see especially the first edition s Section 6.3 for a discussion of iron-sulfur clusters. In this second edition, information on iron-sulfur clusters in nitrogenase is found in Section 3.6.4. See Table 3.2 and the descriptive examples discussed in Section 3.6.4. 

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