Iron–sulfur protein (Fe-S protein)

Iron–sulfur proteins are a fundamental class of proteins containing clusters of iron and sulfur atoms that serve as versatile prosthetic groups (Wikipedia: Iron-sulfur protein). These proteins are essential for life, participating in critical cellular functions such as electron transfer in the mitochondrial respiratory chain, enzymatic catalysis in the citric acid cycle, and the regulation of gene expression (UniProt: Iron-sulfur). They also play a vital role in DNA replication and repair, where Fe-S clusters are necessary for the structural integrity and activity of enzymes like DNA polymerases and helicases (PubMed: PMID 25658414). Mutations or deficiencies in the machinery responsible for Fe-S cluster assembly lead to severe pathological conditions, including Friedreich's ataxia and various mitochondrial myopathies (NIH: Friedreich's ataxia). In the context of drug development, Fe-S proteins are targeted to exploit the metabolic vulnerabilities of cancer cells or to correct deficiencies in biogenesis pathways (PubMed: PMID 29330111). Therapeutic strategies include the use of small molecules that disrupt cluster stability to induce oxidative stress or chelators that influence the availability of iron for cluster formation (PubMed: PMID 22411015).

Other names

Iron-sulfur cluster proteinFe-S cluster proteinFerredoxin-like proteinIron-sulfur enzyme

Disruption of iron-sulfur cluster assembly, inhibition of redox-active enzymes, or induction of oxidative stress through cluster degradation and iron release.