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

Iron-sulfur (Fe-S) cluster-containing enzymes represent a vast and essential class of proteins that utilize inorganic clusters of iron and sulfur as prosthetic groups to perform diverse biological functions. These enzymes are fundamental to life, participating in electron transfer within the mitochondrial respiratory chain (e.g., Complexes I, II, and III), catalyzing key steps in the citric acid cycle (e.g., aconitase), and maintaining genomic stability through DNA replication and repair (e.g., DNA polymerases and helicases) (PubMed: 25307071). The clusters themselves are highly sensitive to reactive oxygen species and iron availability, making these enzymes central sensors and targets of oxidative stress. Dysregulation of Fe-S cluster biogenesis or enzyme function is implicated in a variety of human pathologies, including Friedreich's ataxia, sideroblastic anemia, and various cancers (PubMed: 22508476). Pharmacological intervention involves drugs that either directly inhibit specific Fe-S enzymes, such as metronidazole targeting anaerobic metabolism, or agents like arsenic trioxide that disrupt cluster integrity (PubMed: 23934148). Additionally, therapeutic strategies for biogenesis disorders focus on iron chelation or bypass mechanisms to restore enzymatic activity. Given their ubiquity and critical role in cellular metabolism, targeting Fe-S cluster-containing enzymes requires careful consideration of potential systemic toxicity and off-target effects.

Other names

Iron-sulfur proteinFe-S proteinNon-heme iron proteinIron-sulfur cluster enzyme

Inhibition of catalytic activity, disruption of iron-sulfur cluster stability, or interference with the mitochondrial (ISC) and cytosolic (CIA) cluster assembly machinery.