Proteins with Iron-Sulfur Clusters

One large class of non-heme iron-containing biomolecules involves proteins and enzymes containing iron-sulfur clusters. Iron-sulfur clusters are described in Sections 1.7 (Bioorganometallic Chemistry) and 1.8 (Electron Transfer) as well as in Section 3.6 (Mossbauer Spectroscopy). See especially Table 3.2 and the descriptive examples discussed in Section 3.6.4. Iron-sulfur proteins include rubredoxins, ferrodoxins, and the enzymes aconitase and nitrogenase. The nitrogenase enzyme was the subject of Chapter 6 in the hrst edition of this text—see especially Section 6.3 for a discussion of iron-sulfur clusters. In this 

---

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. 

The fourth state with [Fe4S4]° shown in Table 6.1 was recently described as the most reduced form possible for the Fe-protein s [Fe4S4] cluster.16 Usually, only two oxidation states for a given metal-sulfur cluster are stable. Therefore a stable [Fe4S4]° state in Fe-protein s iron-sulfur cluster (as appears likely from experimental evidence presented in reference 16) would be unique because the cluster would then have three stable oxidation states, [Fe4S4]2+/1+/0. It appears also that the all-ferrous state is only stable in the protein-bound cluster and not for model... 

Tachezy J, Dolezal P (2007) Iron-sulfur proteins and iron-sulfur cluster assembly in organisms with hydrogenosomes and mitosomes. In Martin WF, Muller M (eds) Origin of Mitochondria and Hydrogenosomes. Springer, Berlin Heidelberg New York, pp 1 OS-133... 

Iron-Sulfur Proteins and Iron-Sulfur Cluster Assembly in Organisms with Hydrogenosomes and Mitosomes... 

Whereas many cognate apoenzymes can be reconstituted with iron/sulfur clusters by simple and essentially alchemistic procedures using Fe + and sulfide ions under anaerobic conditions, a highly complex enzymatic machinery is used in vivo for the synthesis of iron/sulfur clusters and their transfer to the target enzymes. Sulfide ions required for cluster synthesis are obtained from cysteine (1) via a persulfide of a protein-bound cysteine residue (2) pyridoxal phosphate is required for the formation of the persulfide intermediate (Fig. 1) (12). 

Iron-sulfurvroteins, also called nonheme-iron proteins, are widely occurring, redox-active proteins, containing iron-sulfur clusters as the prosthetic groups. The clusters consist of equal numbers of iron and sulfide ions, with the iron atoms being coordinated to the protein through cysteine residues. The two most common types of iron-sulfur clusters, the [2Fe-2S] and [4Fe-4S] types, are each coordinated to four cysteine residues, and thus may be written as [(2Fe-2S)-(S-Cys)4] and [(4Fe-4S)-(S-Cys)4], respectively, as illustrated in Fig. 20 (E). 

Early papers suggested that DNICs formation with iron-sulfur clusters occurs via transnitrosylation. It was concluded that external iron ions and LMW thiol ligands are necessary in the process of iron-sulfur cluster disruption by NO (see, e.g., [3, 5, 65, 252, 327, 328]). Nevertheless, recent studies on nitrosylation of the biomimetic compounds imply that the most straightforward and facile pathway of the formation of the Fe(NO)2 type DNICs with iron-sulfur proteins is the direct nitrosylation of [Fe ,(SR) ] clusters [118]. 

It has been appreciated for some time that protein-bound iron-sulfur clusters are important in biological electron transfer reactions and, reasonably, they can be found in a variety of proteins associated with redox systems. Although data are incomplete, the extent to which they are effective in any particular system (i.e., their measured reduction potential) appears to be a function of their position (e.g., buried vs. exposed) in the protein. However, in general, as shown in Figure 12.2, the 4Fe-4S cluster is surrounded by protein-bound cysteine residues, forming sulfur-iron bonds external to the cluster, holding it in place. 

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. 

Probably involved with NifS in iron-sulfur cluster synthesis Possibly accelerate MoFe protein maturation Unknown function... 

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. 

Brazzolotto X, JK Rubach, J Gaillard, S Gambrelli, M Atta, M Fontecave (2006) The [Fe-Fe]-hydrogenase maturation protein HydF from Thermotoga maritima is a GTPase with an iron-sulfur cluster. J Biol Chem 279, 281 769-774. 

In some cases, small biological redox partner proteins such as heme-containing cytochromes, ferredoxins comprising an iron-sulfur cluster, or azurin with a mononuclear Cu site have been used as natural mediators to facilitate fast electron exchange with enzymes. A specific surface site on the redox protein often complements a region on the enzyme surface, and enables selective docking with a short electron tunneling... 

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... 

---