Iron-sulphur clusters

Iron-sulphur clusters are the third type of the widely available electron-transfer sites in biology. They consist of iron ions surrounded by four sulphur ions, either thiolate groups from cysteine residues or inorganic sulphide ions. Regular clusters with one (rubredoxins), two, three, or four (ferredoxins) iron ions are known, as well as a number of more irregular clusters, also with other ligands than cysteine [112,181]. Their reduction potentials vary between -700 and +400 mV [112]. 

The electronic stmcture, spectroscopy, and reduction potential have been thoroughly studied for all common classes of iron-sulphur clusters [52,89,182-191]. In particular, Noodleman and coworkers have performed detailed quantum chemical calculations on iron-sulphur clusters in various spin states [192-198]. It is now settled that rubredoxin contains an iron ion in the high-spin state (quintet for Fe , sextet for Fe ), whereas in the [2Fe-2S] clusters, the two iron ions are both in the high-spin state, but antiferromagntically coupled to form a singlet or doublet state for the oxidised (Ill+ni) and reduced (mixed-valence n+ni) forms, respectively [112,162]. In variance to the Cua site, the unpaired spin is trapped at one of the iron ions in the mixed-valence state. 

The Fe-S distances in the Fe(SCH3)4 model increase from 232 to 242 pm when the site is reduced. This lO-pm increase is similar to what is observed in inorganic model conplexes, but the average distances are shorter in the models, 227 and 236 pm, respectively [199]. Thus, the Fe-S distances are again 5-6 pm too 

At first, the increase in reorganisation energy for the dimeric iron-sulphur clusters (coii jtu ed to the monomeric rubredoxin site) may seem a bit strange. 

---

In mitochondria (Fig. lb), the electron acceptor protein is also a flavoprotein termed NADPH-adrenodoxin reductase (MW 50 kDa) because it was discovered in the adrenal cortex and because it donates its electrons not directly to the P450 but to the smaller redox protein adrenodoxin (MW 12.5 kDa). The two iron-sulphur clusters of this protein serve as electron shuttle between the flavoprotein and the mitochondrial P450. 

Imlay, J.A. (2006) Iron-sulphur clusters and the problems with oxygen, Mol. Microbiol., 59, 1073-1082. 

Fig. 1. Schematic representation of the four basic types of iron-sulphur clusters. The rubredoxin-type and the [2Fe-2S], [3Fe—4S] and [4Fe-4S] clusters are shown in (a) to (d), respectively. Reprint from Prog. Biophys. Mol. Biol., Vol. 70, H. Sticht and P. Rosch, The structure of iron-sulfur proteins , pp. 95-136, Copyright 1998, with permission from Elsevier Science.

Holm, R. H. (1975). Iron-sulphur clusters in natural and synthetic systems. Endeavour 34, 38-43. 

Active Site Structure of Rubredoxin There are several non-heme iron-sulphur proteins that are involved in electron transfer. They contain distinct iron-sulphur clusters composed of iron atoms, sulphydryl groups from cysteine residues and inorganic or labile sulphur atoms or sulphide ions. The labile sulphur is readily removed by washing with acid. The cysteine moieties are incorporated within the protein chain and are thus not labile. The simplest type of cluster is bacteria rubredoxin, (Cys-S)4 Fe (often abbreviated FelSO where S stands for inorganic sulphur), and contains only non labile sulphur. It is a bacterial protein of uncertain function with a molecular weight of 6000. The single iron atom is at the centre of a tetrahedron of four cysteine ligands (Fig.). 

Rouault , Tong WH (2005) Iron-sulphur cluster biogenesis and mitochondrial iron homeostasis. Nat Rev Mol Cell Biol 6 345-351 Roy A, Solodovnikova N, Nicholson T, Antholine W, Walden WE (2003) A novel eukaryotic factor for cytosolic Fe-S cluster assembly. EMBO J 22 4826-4835 Schilke B, Voisine C, Beinert H, Craig E (1999) Evidence for a conserved system for iron metabolism in the mitochondria of Saccharomyces cerevisiae. Proc Natl Acad Sci USA 96 10206-10211... 

Rouault TA, Tong WH (2005) Iron-sulphur cluster biogenesis and mitochondrial iron homeostasis. Nat Rev Mol Cell Biol 6 345-351... 

Mitosomes, hydrogenosomes, and mitochondria all share enzymes involved in the synthesis and assembly of iron-sulphur clusters, but neither an electron-transport chain nor substrate-level ATP synthesis (Gabaldon and Huynen 2003, 2004) is common to them all. Moreover, since the original endosymbiont for sure lacked ATP-exporting proteins, it is likely that the original endosymbiosis was not driven by providing ATP to the host (Martin... 

The first metal-sulphide clusters were recognized in photosynthetic centres of all plants, nitrogen-fixing bacteria, and mitochondrial proteins of mammalian origin. It soon turned out that all these proteins contain closely related iron-sulphur clusters (Figure 10.3). More recent studies indicated that iron-sulphur proteins are ubiquitous in all living matter, including extremophilic Archaebacteria. 

Iron-sulphur clusters constitute integral parts of several natural structures occurring in a large family of biologically relevant metalloproteins. The [Fe-S] units... 

Flitney FW, Megson IL, Flitney DE, Butler AR. Iron-sulphur cluster nitrosyls, a novel class of nitric oxide generator mechanism of vasodilator action on rat isolated tail artery. Br J Pharmacol 1992 107 842. 

Matthews EK, Seaton ED, Forsyth MJ, Humphrey PPA. Photon pharmacology of an iron-sulphur cluster nitrosym compound acting on smooth muscle. Br J Pharmacol 1994 113 87. 

Steenkamp, D. J., Singer, T. P., and Beinert, H., 1978c, Participation of the iron-sulphur cluster and of the covalently bound coenzyme of trimethylamine dehydrogenase in catalysis, Biochem. J. 169 361n9. 

Albracht SPJ, van derZwaan JW, Fontijn RD, Slater EC (1986) On the possible redox states of nickel and the iron-sulphur cluster in hydrogenase from Chromatium vinosum. In Xavier AV (ed) Frontiers in bioinorganic Chemistry. VCH, Weinheim, pp 11-19... 

Figure 2.29. Detail of photosystem I, seen from the side, with the division between units A and B (see Fig. 2.27) in the middle. Chlorophyll molecules (chi) other than the six central ones involved in transfer of energy to the three Fe4S4 clusters (FeS) are omitted. Chlorophylls, phylloquinones (phy, also known as vitamin K) and iron-sulphur clusters are further indexed with the subimit label A, B or X (cf. Fig. 2.27), and the chlorophylls are shown with an index number 1 to 3. Other identified molecules include LHG (CggHygOjoP), LMG (C45H84OJQ) and a number of p-carotenes (BCR). The scattered dots are oxygen atoms of water molecules (no hydrogens are shown). Based on Protein Data Bank ID IJBO Jordan et ah, 2001).

While the protein chain C surroimding the iron-sulphur clusters (Fig. 2.28) is similar in structure to ferredoxin, it needs a real ferredoxin protein docked on the stroma side to transfer the electron from FeS-B away from PS I. The subsystems C, D and E on the stroma side of PS I (Fig. 2.27) allow docking not only of the fairly small ferredoxin system (an example of which is shown in Fig. 2.30 - there are variations in structure between species such as plants and cyanobacteria), but also of the larger flavodoxin protein (Fromme et al, 2003), an example of which is shown in Fig. 2.31. 

The proposed catalytic mechanism of the ferredoxin oxidoreductase [32] is shown in Fig. 4, a similar mechanism existing for the analogous citric acid cycle enzyme, 2-oxoglutarate oxidoreductase. In outline, the 2-oxoacid is decarboxylated in a TPP-dependent reaction to give an hydroxyalkyl-TPP. From this, one electron is abstracted and transferred to the enzyme-bound iron-sulphur cluster, generating a free-radical-TPP species. This intermediate can then interact direct with coenzyme-A to form acyl-CoA, the iron-cluster receiving the second electron. In each case, ferredoxin serves to re-oxidise the enzyme s redox centre. 

---