Iron-sulfur cluster-containing protein (Fe-S protein) (Fe-S protein)

Iron-sulfur cluster-containing proteins are a diverse and essential class of metalloproteins characterized by the presence of iron and sulfur atoms coordinated by amino acid side chains, most commonly cysteine (NIH, 2024). They play fundamental roles in life-sustaining processes, including mitochondrial respiration in Complexes I, II, and III, DNA replication and repair via polymerases and helicases, and metabolic catalysis through enzymes like aconitase (Wikipedia, 2024; NIH, 2018). Beyond these roles, they function as sensitive sensors for cellular iron, oxygen, and nitric oxide levels, allowing cells to adapt to environmental changes (PubMed, 2024). Dysregulation or genetic mutations in Fe-S cluster biogenesis pathways lead to severe human diseases, such as Friedreich's ataxia, sideroblastic anemia, and various mitochondrial myopathies (NIH, 2010; NIH, 2024). In oncology, certain Fe-S proteins like NAF-1 (CISD2) are overexpressed in aggressive tumors to manage oxidative stress, making them attractive targets for anticancer therapy (MDPI, 2022; LabMedica, 2016). Drugs like pioglitazone have been shown to interact with and stabilize these clusters, while other strategies involve disrupting cluster assembly to induce ferroptosis in cancer cells (NIH, 2023; Encyclopedia.pub, 2023). Additionally, Fe-S clusters are targets for antimicrobial and antiviral strategies, as seen in the SARS-CoV-2 RNA-dependent RNA polymerase (NIH, 2023). The ubiquity and sensitivity of these clusters to reactive oxygen species make them critical nodes in cellular redox homeostasis and potential sites for drug-induced toxicity (NIH, 2016).

Other names

Iron-sulfur proteinISC proteinMetalloprotein with iron-sulfur clustersFerredoxinRieske protein

Cluster stabilization, inhibition of cluster assembly, cluster disruption, iron chelation, and redox modulation (NIH, 2023; MDPI, 2022).