In biochemistry, the iron-sulfur cluster biosynthesis describes the components and processes involved in the biosynthesis of
iron-sulfur protein
Iron–sulfur proteins (or iron–sulphur proteins in British spelling) are proteins characterized by the presence of iron–sulfur clusters containing sulfide-linked di-, tri-, and tetrairon centers in variable oxidation states. Iron–sulfur cl ...
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 (S2-), 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 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 S atom is obtained from cysteine by the action of so-called
cysteine desulfurases. One prominent desulfurase is called Isc. Not only is cysteine the source of S, Furthermore, a cysteine residue is the partner protein IscU plays a role is relaying the S atom to iron.
The enzyme IscS catalyzes the abstraction of a sulfur atom from cysteine. IscS is 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-dependent ...
-dependent enzyme. The sulfur atom becomes inserted into the S-H bond of residue Cys-328 of IscS attacks the sulfur atom of L-cysteine, and the sulfane sulfur derived from L-cysteine binds to the S atom of Cys-328, forming a
persulfide:
:L-cysteine +
nzymecysteine
L-alanine +
nzymeS-sulfanylcysteine
The persulfide contains the
functional group
In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the r ...
R-S-S-H, which functions as a source of "inorganic sulfur" that will comprise the Fe-S proteins. Subsequently, the IscS transfers its "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 chaparones.
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References
{{InterPro content, IPR000361
Protein families