Iron-sulfur protein

Iron-sulfur proteins are proteins characterized by the presence of iron-sulfur clusters containing sulfide-linked di-, tri-, and tetrairon centers in variable oxidation states. Iron-sulfur clusters are found in a variety of metalloproteins, such as the ferredoxins, as well as NADH dehydrogenase, hydrogenases, Coenzyme Q - cytochrome c reductase, Succinate - coenzyme Q reductase and nitrogenase. [S. J. Lippard, J. M. Berg “Principles of Bioinorganic Chemistry” University Science Books: Mill Valley, CA; 1994. ISBN 0-935702-73-3.] Iron-sulfur clusters are best known for their role in the oxidation-reduction reactions of mitochondrial electron transport. Both Complex I and Complex II of oxidative phosphorylation have multiple Fe-S clusters. They have many other functions including catalysis as illustrated by aconitase, generation of radicals as illustrated by SAM-dependent enzymes, and as sulfur donors in the biosynthesis of lipoic acid and biotin. Additionally some Fe-S proteins regulate gene expression. Fe-S proteins are vulnerable to attack by biogenic nitric oxide.

tructural motifs

In almost all Fe-S proteins, the Fe centers is tetrahedral and the thiolato sulfur centers, from cysteinyl residues, are terminal ligands. The sulfide groups are either two- or three-coordinated. Three distinct kinds Fe-S clusters with these features are most common.

2Fe-2S clusters

s). The oxidized proteins contain two Fe³⁺ ions, whereas the reduced proteins contain one Fe³⁺ and one Fe²⁺ ion. These species exist in two oxidation states, (Fe^III)₂ and Fe^IIIFe^II.

4Fe-4S clusters

A common motif features a four iron ions and four sulfide ions placed at the vertices of a cubane-type structure. The Fe centers are typically further coordinated by cysteinyl ligands. The [Fe₄S₄] electron-transfer proteins ( [Fe₄S₄] ferredoxins) may be further subdivided into low-potential (bacterial-type) and high-potential (HiPIP) ferredoxins. Low- and high-potential ferredoxins are related by the following redox scheme:

In HiPIP, the cluster shuttles between [2Fe³⁺, 2Fe²⁺] (Fe₄S₄²⁺) and [3Fe³⁺, Fe²⁺] (Fe₄S₄³⁺). The potentiasl for this redox couple range from 0.4 to 0.1 V. In the bacterial Fd's, the pair of oxidation states are [Fe³⁺, 3Fe²⁺] (Fe₄S₄⁺) and [2Fe³⁺, 2Fe²⁺] (Fe₄S₄²⁺). The potentials for this redox couple range from -0.3 to -0.7 V. The two families of 4Fe-4S clusters share the Fe₄S₄²⁺ oxidation state. The difference in the redox couples is attributed to the degree of hydrogen bonding, which strongly modified the basicity of the cysteinyl thiolate ligands. A further redox couple, which is still more reducing than the bacterial Fd's is implicated in the nitrogenase.

Some 4Fe-4S clusters bind substrates and are thus classified as enzymes. In aconitase, the Fe-S cluster binds aconitate at the one Fe centre that lacks a thiolate ligand. The cluster does not undergo redox, but serves as a Lewis acid catalyst to convert aconitate to isocitrate. In the radical-SAM enzymes, the cluster binds and reduces S-adenosylmethionine to generate a radical, which is involved in many biosyntheses. [cite journal | author = Susan C. Wang and Perry A. Frey | title = S-adenosylmethionine as an oxidant: the radical SAM superfamily | journal = Trends in Biochemical Sciences | year = 2007 | volume = 32 | pages = 101 | doi = 10.1016/j.tibs.2007.01.002]

3Fe-4S clusters

Proteins are also known to contain [Fe₃S₄] centres, which feature one iron less than the more common [Fe₄S₄] cores. Three sulfide ions bridge two iron ions each, while the fourth sulfide bridges three iron ions. Their formal oxidation states may vary from [Fe₃S₄] ⁺ (all-Fe³⁺ form) to [Fe₃S₄] ^2- (all-Fe²⁺ form). In a number of iron-sulfur proteins, the [Fe₄S₄] cluster can be reversibly converted by oxidation and loss of one iron ion to a [Fe₃S₄] cluster. E.g., the inactive form of aconitase possesses an [Fe₃S₄] and is activated by addition of Fe²⁺ and reductant.

Other Fe-S clusters

More complex polymetallic systems are common. Examples include both the 8Fe and the 7Fe clusters in nitrogenase. Carbon monooxide dehydrogenase and the FeFe-hydrogenase also feature unusual Fe-S clusters.

Biosynthesis

The biosynthesis of the Fe-S clusters has been well studied. [cite journal | author = Johnson D, Dean DR, Smith AD, Johnson MK | title = Structure, function and formation of biological iron–sulfur clusters | journal = Annual Review of Biochemistry | year = 2005 | volume = 74 | pages = 247–281 | doi = 10.1146/annurev.biochem.74.082803.133518] [Johnson, M.K. and Smith, A.D. (2005) Iron–sulfur proteins in: Encyclopedia of Inorganic Chemistry (King, R.B., Ed.), 2nd edn, John Wiley & Sons, Chichester.] [cite journal | author = Lill R, Mühlenho U | title = Iron–sulfur-protein biogenesis in eukaryotes | journal = Trends in Biochemical Sciences | year = 2005 | volume = 30 | pages = 133–141 | doi = 10.1016/j.tibs.2005.01.006] The biogenesis of iron sulfur clusters has been studied most extensively in the bacteria "E. coli" and "A. vinelandii" and yeast "S. cerevisiae". At least three different biosynthetic systems so far identified, namely nif, suf, and isc systems, which were first identified in bacteria. The nif system is responsible the clusters in the enzyme nitrogenase. The suf and isc systems are more general with the isc-related proteins being the only present in the animal kingdom. The yeast isc system is the best described. Several proteins constitute the biosynthetic machinery via the isc pathway. The process occurs in two major steps:1)the Fe/S cluster is assembled on a scaffold protein followed by transfer of the preformed cluster to the recipient proteins.The first step of this process occurs in the cytoplasm of procaryotic organisms or in the mitochondria of eucaryotic organisms. In the higher organisms the clusters are therefore transported out of the mitochondrion to be incorporated into the extramitochondrial enzymes. These organisms also possess a set of proteins involved in the Fe/S clusters transport and incorporation processes that are not homologous to proteins found in procaryotic systems.

ynthetic analogues

Synthetic analogues of the naturally occurring Fe-S clusters were first reported by Holm and coworkers. [cite journal | author = T. Herskovitz, B. A. Averill, R. H. Holm, J. A. Ibers, W. D. Phillips and J. F. Weiher | title = Structure and Properties of a Synthetic Analogue of Bacterial Iron-Sulfur Proteins | year = 1972 | journal = Proceedings of the National Academy of Sciences | volume = 69 | issue = 9 | pages = 2437–2441 | doi = 10.1073/pnas.69.9.2437 | pmid = 4506765] Treatment of iron salts with a mixture of thiolates and sulfide affords derivatives such as (Et₄N)₂Fe₄S₄(SCH₂Ph)₄] .

References

Further reading

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External links

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ee also

* Bioinorganic chemistry

External links

* [http://metallo.scripps.edu/PROMISE/2FE2S.html Examples of iron-sulfur clusters]