Iron—sulfur proteins examples

Iron-Sulfur Proteins (Examples FeS4 - and Fe4S4 - Centers)... 

Resonance Raman (RR) spectroscopy provides information about the vibrational characteristics of a chromophore, for example, a metal center, within the complex environment of a protein. In RR spectra, those vibrational transitions are observed selectively that are coupled to electronic transitions. In iron sulfur proteins, this technique has been used to resolve the complex electronic absorption spectra and to identify both vibrational and electronic transitions. 

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). 

Although iron-sulfur proteins are found in various cellular localizations in eukaryotic cells, mitochondria are the major site of Fe-S cluster biosynthesis (Lill et ah, 1999). Deletions in nuclear genes involved in mitochondrial iron-sulfur cluster formation lead to massive accumulation of iron in mitochondria (Chapter 7). For example, deletion of ATM1, a mitochondrial ATPase, which seems to be responsible for the export of Fe-S clusters, leads to respiratory incompetence, excessive iron accumulation and leucine auxotrophy (Kispal et ah, 1999). In Ayfhl cells there is only partial loss of mitochondrial Fe-S enzymes and the cells are not leucine auxotrophs. 

XAS data comprises both absorption edge structure and extended x-ray absorption fine structure (EXAFS). The application of XAS to systems of chemical interest has been well reviewed (4 5). Briefly, the structure superimposed on the x-ray absorption edge results from the excitation of core-electrons into high-lying vacant orbitals (, ] ) and into continuum states (8 9). The shape and intensity of the edge structure can frequently be used to determine information about the symmetry of the absorbing site. For example, the ls+3d transition in first-row transition metals is dipole forbidden in a centrosymmetric environment. In a non-centrosymmetric environment the admixture of 3d and 4p orbitals can give intensity to this transition. This has been observed, for example, in a study of the iron-sulfur protein rubredoxin, where the iron is tetrahedrally coordinated to four sulfur atoms (6). 

The relevant structural and chemical information on iron-sulfur proteins provided by EPR, ENDOR and Mossbauer techniques serves as an instructive example for the success of combining different types of spectroscopic methods. 

The next class of iron-sulfur proteins contains Fe3S4 clusters. The commonest example of such proteins is that of 3Fe ferredoxins, which are found in bacteria. As shown in Figure 23, in these proteins the Fe3S4 cluster belongs to the class previously defined as having an incomplete cuboidal geometry (Chapter 8, Section l.l).46... 

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. 

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... 

Iron-sulfur proteins serve predominantly as electron carriers (28,29). The best understood examples are those proteins with IFe, 2Fe, and 4Fe centers. The environment of the mononuclear iron center, rubredoxin, is shown in structure C (17). It consists of a distorted tetrahedral array of sulfur atoms from cysteine residues at nearly equal distances from the iron atom. Crystal structures are available for 2Fe-2S ferredoxins from Spindina plantensis (19) and Aphanothece sacrum (20). A representation of the geometry of this site is given in structure D. The 2Fe-2S core is anchored to the polypeptide by ligation to 4 cysteine sulfur atoms, yielding distorted tetrahedral geometry for both iron atoms. Crystal... 

Megaredoxin. Another example of a bacterial mixed-function oxidase was found in the steroid 15 6-hydroxylase system of Bacillus megaterium (41). This enzyme system consists of three proteins FMN-containing flavoprotein (megaredoxin reductase), iron-sulfur protein... 

FIGURE 19-5 Iron-sulfur centers. The Fe-S centers of iron-sulfur proteins may be as simple as (a), with a single Fe ion surrounded by the S atoms of four Cys residues. Other centers include both inorganic and Cys S atoms, as in (b) 2Fe-2S or (c) 4Fe-4S centers, (d) The ferredoxin of the cyanobacterium Anabaena 7120 has one 2Fe-2S center (PDB ID 1 FRD) Fe is red, inorganic S2 is yellow, and the S of Cys is orange. (Note that in these designations only the inorganic S atoms are counted. For example, in the 2Fe-2S center (b), each Fe ion is actually surrounded by four S atoms.) The exact standard reduction potential of the iron in these centers depends on the type of center and its interaction with the associated protein. 

A second group of electron carriers in mitochondrial membranes are the iron-sulfur [Fe-S] clusters which are also bound to proteins. Iron-sulfur proteins release Fe3+ or Fe2+ plus H2S when acidified. The "inorganic clusters" bound into the proteins have characteristic compositions such as Fe2S2 and Fe4S4. The sulfur atoms of the clusters can be regarded as sulfide ions bound to the iron ions. The iron atoms are also attached to other sulfur atoms from cysteine side chains from the proteins. The Fe-S proteins are often tightly associated with other components of the electron transport chain. For example, the flavoproteins Flavin 1, Flavin 2, and Flavin 3 shown in Fig. 10-5 all contain Fe-S clusters as does the Q-cytochrome b complex. All of these Fe-S clusters seem to be one-electron carriers. 

If an enzyme binds a flavin radical much more tightly than the fully oxidized or reduced forms, reduction of the flavoprotein will take place in two one-electron steps. In such proteins the values of E° for the two steps may be widely separated. The best known examples are the small, low-potential electron-carrying proteins known as flavodoxins.266 269a These proteins, which carry electrons between pairs of other redox proteins, have a variety of functions in anaerobic and photosynthetic bacteria, cyanobacteria, and green algae. Their functions are similar to those of the ferredoxins, iron-sulfur proteins that are considered in Chapter 16. 

Cytochromes b, a, and o. Protoheme-containing cytochromes b are widely distributed.127,128 There are at least five of them in E. coli. Whether in bacteria, mitochondria, or chloroplasts, the cytochromes b function within electron transport chains, often gathering electrons from dehydrogenases and passing them on to c-type cytochromes or to iron-sulfur proteins. Most cytochromes b are bound to or embedded within membranes of bacteria, mitochondria, chloroplasts, or endoplasmic reticulum (ER). For example, cyto-... 

The emphasis on the study of hemoproteins and the iron-sulfur proteins often distracts attention from other iron proteins where the iron is bound directly by the protein. A number of these proteins involve dimeric iron centres in which there is a bridging oxo group. These are found in hemerythrin (Section 62.1.12.3.7), the ribonucleotide reductases, uteroferrin and purple acid phosphatase. Another feature is the existence of a number of proteins in which the iron is bound by tyrosine ligands, such as the catechol dioxygenases (Section 62.1.12.10.1), uteroferrin and purple acid phosphatase, while a tyrosine radical is involved in ribonucleotide reductase. The catecholate siderophores also involve phenolic ligands (Section 62.1.11). Other relevant examples are transferrin and ferritin (Section 62.1.11). These iron proteins also often involve carboxylate and phosphate ligands. These proteins will be discussed in this section except for those relevant to other sections, as noted above. 

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