Sulfide:quinone oxidoreductase (SQR)

Sulfide:quinone oxidoreductase (SQR) is an integral peripheral membrane enzyme that catalyzes the oxidation of sulfide ions to elemental sulfur, transferring electrons to membrane quinones such as ubiquinone, menaquinone, or plastoquinone. The enzyme contains a covalently bound FAD cofactor and conserved cysteine residues crucial for its catalytic mechanism, which involves the formation of sulfur bridges and polysulfur chains at the active site. SQR plays a vital role in sulfide detoxification and in mitochondrial and microbial energy metabolism, supporting ion gradient formation for ATP synthesis. Its structural family is closely related to other disulfide oxidoreductase flavoproteins, and its activity is essential for survival in sulfide-rich or hypoxic environments. Increased SQR expression mediates protection against hypoxia in animal models. Inhibitors such as Aurachin C can competitively block the quinone-binding site, impeding the electron transfer essential for its function. Dysfunction or inhibition of SQR may contribute to energy metabolism disorders and heightened toxicity due to sulfide accumulation.

Other names

Sulfide:quinone reductaseSQRsulfide:quinone oxidoreductase (systematic name)EC 1.8.5.4

Inhibitors block electron transfer to quinone (e.g., competitive inhibition at the quinone binding site). Drugs could act by preventing sulfide oxidation or interfering with energy/redox balance; no FDA-approved drugs target SQR directly at present.