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Literature summary for extracted from

  • Landry, A.P.; Moon, S.; Bonanata, J.; Cho, U.S.; Coitino, E.L.; Banerjee, R.
    Dismantling and rebuilding the trisulfide cofactor demonstrates its essential role in human sulfide quinone oxidoreductase (2020), J. Am. Chem. Soc., 142, 14295-14306 .
    View publication on PubMedView publication on EuropePMC

Crystallization (Commentary)

Crystallization (Comment) Organism
purified SQOR-CoQ1 complexed with cyanide, hanging drop vapor diffusion method, mixing of 17.4 mg/ml solubilized human SQOR in 50 mM Tris-HCl, pH 8.0, 300 mM NaCl, 0.05% w/v n-dodecyl beta-D-maltoside, and 5 mM CoQ1 (in 100% DMSO), with reservoir solution composed of 200 mM ammonium tartrate dibasic, pH 6.6, and 20% w/v PEG 3350, yielding a final CoQ1 concentration of 2.5 mM, in a 1:1 ratio, at 20°C, soaking of crystals with 10 mM potassium cyanide solution for 45 min, X-ray diffraction structure determination analysis at 2.25 A resolution, molecular replacement using a SQOR-CoQ1 structure (PDB ID 6OIB) as a search model, structure modeling Homo sapiens

General Stability

General Stability Organism
cyanolysis of the bridging sulfur decreases enzyme SQOR protein stability Homo sapiens


Inhibitors Comment Organism Structure
cyanide cyanide treatment destabilized human SQOR and leads to its inactivation with concomitant loss of the bridging sulfane sulfur. Addition of sulfide to inactive cyanide treated enzyme leads to recovery of active SQOR, indicating that the oxidation state of the active site cysteines is preserved upon cyanide treatment. Crystallization of SQOR with cyanide led to the capture of a 379Cys N-(201Cys-disulfanyl)-methanimido thioate intermediate. Spectral and kinetic characterization of cyanolysis-induced dismantling followed by sulfide-dependent rebuilding of the trisulfide cofactor, proposed mechanism for cyanolysis and cysteine trisulfide rebuilding in SQOR, overview Homo sapiens


Localization Comment Organism GeneOntology No. Textmining
mitochondrial inner membrane membrane-anchored Homo sapiens 5743

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
hydrogen sulfide + glutathione + coenzyme Q Homo sapiens
S-sulfanylglutathione + reduced coenzyme Q


Organism UniProt Comment Textmining
Homo sapiens Q9Y6N5


Reaction Comment Organism Reaction ID
hydrogen sulfide + glutathione + a quinone = S-sulfanylglutathione + a quinol the reaction cycle proceeds via two half reactions. In the first half reaction, sulfide adds to the trisulfide at the solvent-accessible Cys379 to form a 379Cys-SSH persulfide. The bridging sulfur is retained on 201Cys-SS- persulfide, which forms an unusually intense charge transfer (CT) complex with FAD. Sulfur transfer from 379Cys-SSH to a small molecule acceptor leads to regeneration of the active site trisulfide with the concomitant two-electron reduction of FAD. In the second half reaction, FADH2 transfers electrons to CoQ10, regenerating the resting enzyme and linking sulfide oxidation to mitochondrial energy metabolism by supplying reduced CoQ10 to Complex III in the electron transport chain Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
hydrogen sulfide + glutathione + coenzyme Q
Homo sapiens S-sulfanylglutathione + reduced coenzyme Q
additional information the rate of sulfide addition to the cysteine trisulfide of SQOR is estimated to much higher than the rate of sulfide addition to cysteine disulfide in solution. The subsequent formation of persulfide rather than thiolate intermediate on Cys201 also enhances its reactivity for facilitating sulfur transfer and electron movement via the putative C4a adduct. Computational modeling, overview Homo sapiens ?
Na2S + glutathione + coenzyme Q1
Homo sapiens S-sulfanylglutathione + reduced coenzyme Q1 + 2 Na+


Synonyms Comment Organism
Homo sapiens
sulfide quinone oxidoreductase
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
assay at Homo sapiens


Cofactor Comment Organism Structure
coenzyme Q
Homo sapiens
FAD required Homo sapiens
additional information molecular dynamics simulations and QM/MM reactivity predictors for a disulfide versus trisulfide cofactor involving FAD, overview Homo sapiens

General Information

General Information Comment Organism
evolution sulfide quinone oxidoreductase (SQOR) is a member of the flavin disulfide reductase superfamily Homo sapiens
malfunction cyanolysis leads to reversible loss of SQOR activity that is restored in the presence of sulfide. Inherited deficiency of SQOR presents as Leigh disease. Cyanolysis of the bridging sulfur decreases enzyme SQOR protein stability Homo sapiens
metabolism sulfide quinone oxidoreductase (SQOR) catalyzes the first step in sulfide clearance, coupling H2S oxidation to coenzyme Q reduction Homo sapiens
additional information structures of human SQOR reveal a sulfur atom bridging the SQOR active site cysteines in a trisulfide configuration. Computational modeling and molecular dynamics simulations revealed an about 105fold rate enhancement for nucleophilic addition of sulfide into the trisulfide versus a disulfide cofactor. The cysteine trisulfide in SQOR is thus critical for activity and provides a significant catalytic advantage over a cysteine disulfide. Descriptors of intrinsic reactivity derived from the electronic structure of Cys379 and Cys201 are calculated at the QM/MM level in the framework of a conceptual DFT. DFT-PCM modeling of reaction mechanisms and barriers for sulfide nucleophilic attack, detailed overview Homo sapiens
physiological function hydrogen sulfide (H2S) is a signaling molecule that exerts physiological effects in the cardiovascular, central nervous, and gastrointestinal systems. At higher concentrations, H2S can act as a respiratory poison that blocks the electron transport chain by inhibiting complex IV. Due to the dual effects of H2S, its levels must be strictly regulated. The accumulation of toxic concentrations of H2S is prevented by its oxidation to thiosulfate and sulfate via the mitochondrial sulfide oxidation pathway. The first and committed step in this pathway is catalyzed by sulfide quinone oxidoreductase (SQOR), an inner mitochondrial membrane-anchored flavoprotein. SQOR catalyzes coupling of H2S oxidation to coenzyme Q reduction. It transfers the oxidized sulfane sulfur to a small molecule acceptor, which is predicted to be glutathione (GSH) under physiological conditions Homo sapiens