In biochemistry, the iron–sulfur cluster biosynthesis describes the components and processes involved in the biosynthesis of
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 ...
s. The topic is of interest because these proteins are pervasive. The iron sulfur proteins contain iron–sulfur clusters, some with elaborate structures, that feature iron and sulfide centers. One broad biosynthetic task is producing sulfide (S
2-), which requires various families of enzymes. Another broad task is affixing the sulfide to iron, which is achieved on scaffolds, which are nonfunctional. Finally these Fe-S cluster is transferred to a target protein, which then become functional.
The formation of iron–sulfur clusters are produced by one of four pathways:
*Nitrogen fixation (NIF) system, which is also found in bacteria that are not nitrogen-fixing.
*Iron–sulfur cluster (ISC) system, in bacterial and mitochondria
*Sulfur assimilation (SUF) system, in
plastids
A plastid is a membrane-bound organelle found in the cells of plants, algae, and some other eukaryotic organisms. Plastids are considered to be intracellular endosymbiotic cyanobacteria.
Examples of plastids include chloroplasts (used for photo ...
and some bacteria
In addition to those three systems, the so-called Cystosolic Iron–sulfur Assembly (CIA) is invoked for cytosolic and nuclear Fe–S proteins.
Mechanisms
The assembly of iron–sulfur clusters cluster begins with the production of the equivalent of a sulfur (sulfur atoms per se are not found in nature). The required sulfur atom is obtained from free cysteine by the action of so-called
cysteine desulfurase
In enzymology, a cysteine desulfurase () is an enzyme that catalyzes the chemical reaction
:L-cysteine + nzymecysteine \rightleftharpoons L-alanine + nzymeS-sulfanylcysteine
Thus, the two substrates of this enzyme are L-cysteine and nzymecy ...
s. One prominent desulfurase is called IscS, a
pyridoxal phosphate
Pyridoxal phosphate (PLP, pyridoxal 5'-phosphate, P5P), the active form of vitamin B6, is a coenzyme in a variety of enzymatic reactions. The International Union of Biochemistry and Molecular Biology has catalogued more than 140 PLP-dependen ...
-dependent enzyme. The sulfur atom from the cysteine substrate is transferred to residue Cys-328 of IscS, forming a
persulfide
In chemistry, persulfide refers to the functional group R-S-S-H. Persulfides are intermediates in the biosynthesis of iron-sulfur proteins and are invoked as precursors to hydrogen sulfide, a signaling molecule.
Nomenclature
The nomenclature use ...
:
:L-cysteine +
nzymecysteine
L-alanine +
nzymeS-sulfanylcysteine
The persulfide
functional group
In organic chemistry, a functional group is any substituent or moiety (chemistry), moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions r ...
R-S-S-H functions as a source of "inorganic sulfur" that will be incorporated into Fe-S clusters. Subsequently, IscS transfers this "extra" sulfur to IscU.
In addition to IscS and IscU, bacterial Fe-S assembly requires IscA, an 11 kDa protein of uncertain function.
The Suf system for iron–sulfur cluster biosynthesis is generally similar to the Isc system (and the Nif system). The analogy extends to the existence of SufA, SufS, and SufU. The Suf system operates with fewer
chaperones.
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References
{{InterPro content, IPR000361
Protein families