Iron-sulfur clusters

(4Fe-4S) as a cofactor in aconitase according to PDB 7ACN . Also shown are the -S- bound cysteine ​​residues of the protein that fix the cluster.

(2Fe-2S) cofactor as found in cytochrome bc ₁ or cytochrome b ₆ f .

Activation of the iron-sulfur cluster by the fourth iron atom. The conformation changes from tetrahedron to octahedron.

Nitrogenase cofactor

Iron-sulfur clusters ( Fe-S centers ) are multiple complexes of iron and sulfur the size of clusters that are involved as cofactors in enzyme reactions. The most common and stable are (4Fe-4S) and (2Fe-2S). In general, clusters are destroyed when they are accessible to free oxygen. Accessibility depends on the protection of the binding enzyme.

These Fe-S centers act as electron transfer reactants , Lewis acids and radical generators in enzymes . For example, nitrogen can be converted into ammonia , hydrogen into protons and carbon monoxide into carbon dioxide :

${\displaystyle \mathrm {N_{2}+10\ H^{+}+8\ e^{-}\longrightarrow 2\ NH_{4}^{+}+H_{2}} }$

${\displaystyle \mathrm {H_{2}\longrightarrow 2\ H^{+}+2\ e^{-}} }$

${\displaystyle \mathrm {CO+H_{2}O\longrightarrow CO_{2}+2\ H^{+}+2\ e^{-}} }$

The iron atoms of the centers are coordinated by inorganic sulfide and the side chains of amino acids . For example, cysteines can coordinate via their thiol group (see Fig.).

biosynthesis

Even under reducing, aqueous conditions, rhombic (2Fe-2S) complexes form spontaneously . Other metal ions, e.g. B. nickel or molybdenum can be included in the complex in a row. This happens particularly effectively in the organism with the participation of a protein complex that contains the iron-sulfur cluster framework protein (ISCU).

ISCU takes on the role of binding the iron atoms that are transported by ISCA, while the enzyme cysteine ​​desulfurase provides sulfur atoms with cysteine ​​consumption . First, (2Fe-2S) is put together, which eventually becomes (4Fe-4S) through dimerization. This process can take place in the mitochondria as well as in the cytosol, after which the finished (4Fe-4S) is transported into the plasma or incorporated into ready-made enzymes.

Occurrence

Anaerobic live bacteria and archaea partially also contain oxygen-sensitive enzymes with a nickel-, iron- and sulfur-containing center that the cluster C is referred to.

The enzyme nitrogenase contains an Fe-Mo-S cluster as a cofactor.

Iron-sulfur clusters are found in mitochondria, mitosomes, and hydrogenosomes.

List of human proteins with (2Fe-2S)

• NADH dehydrogenase , succinate dehydrogenase and cytochrome c reductase (complex I, II and III of the respiratory chain , citric acid cycle )
• Adrenodoxin (synthesis of thyroid hormones )
• Xanthine oxidase ( nucleotide metabolism )
• Aldehyde oxidase ( biotransformation , breakdown of nicotine )
• Ferrochelatase ( porphyrin metabolism )
• Miner1 and Miner2

List of human proteins with (4Fe-4S)

• NADH dehydrogenase and succinate dehydrogenase (complex I and II of the respiratory chain, citric acid cycle)
• Aconitase (citric acid cycle)
• Amidophosphoribosyltransferase ( purine metabolism , inosine monophosphate - de novo synthesis )
• Dihydropyrimidine dehydrogenase (amino acid synthesis, synthesis of β- alanine )
• IREBP2 (iron metabolism)
• Lipoyl synthase (protein modification)
• the core enzymes DNA primase and endonuclease III-like

See also

• Ferredoxin

literature

• H. Dobbek: How biological Fe-S centers activate CO2 . In: News from chemistry . tape 56 , no. 7–8 , 2008, pp. 734-737 , doi : 10.1002 / nadc.200857949 .

Individual evidence

1. ↑ Beinert H: Iron-sulfur proteins: ancient structures, still full of surprises . In: J. Biol. Inorg. Chem. . 5, No. 1, February 2000, pp. 2-15. doi : 10.1007 / s007750050002 . PMID 10766431 .
2. ↑ Rouault TA, Tong WH: Iron-sulfur cluster biogenesis and human disease . In: Trends Genet. . 24, No. 8, August 2008, pp. 398-407. doi : 10.1016 / j.tig.2008.05.008 . PMID 18606475 . PMC 2574672 (free full text).
3. ↑ Chandramouli K, Unciuleac MC, Naik S, Dean DR, Huynh BH, Johnson MK: Formation and properties of [4Fe-4S] clusters on the IscU scaffold protein . In: Biochemistry . 46, No. 23, June 2007, pp. 6804-11. doi : 10.1021 / bi6026659 . PMID 17506525 .
4. ↑ Yang J, Bitoun JP, Ding H: Interplay of IscA and IscU in biogenesis of iron-sulfur clusters . In: J. Biol. Chem. . 281, No. 38, September 2006, pp. 27956-63. doi : 10.1074 / jbc.M601356200 . PMID 16877383 .