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Literature summary for 1.8.5.8 extracted from

  • Jackson, M.R.; Loll, P.J.; Jorns, M.S.
    X-ray structure of human sulfide quinone oxidoreductase insights into the mechanism of mitochondrial hydrogen sulfide oxidation (2019), Structure, 27, 794-805.e4 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 1.8.5.8

Application

Application Comment Organism
drug development the enzyme is a target for structure-based drug design Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
purified selenomethionine-substituted and native enzyme, X-ray diffraction structure determination analysis at 2.59 and 2.99 A resolution, respectively, the SeMet and native structures are essentially identical Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
mitochondrial membrane integral membrane protein, the two C-terminal helices lie in the plane of the mitochondrial membrane, with their hydrophobic faces communicating with the membrane interior. This monotopic mode of association allows the enzyme to gain access to its hydrophobic electron acceptor, CoQ Homo sapiens 31966
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Natural Substrates/ Products (Substrates)

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

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9Y6N5
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Reaction

Reaction Comment Organism Reaction ID
hydrogen sulfide + glutathione + a quinone = S-sulfanylglutathione + a quinol proposed model for catalysis. The human SQOR reaction is initiated by nucleophilic attack of HS- at the distal cysteine, Cys379, to produce a charge-transfer (CT) complex of FAD with either Cys201S- or Cys379SS- (step 1). Nucleophilic attack of Cys201S- at the C(4a) position of FAD produces a covalent flavin adduct, 4a-adduct I (step 2). Reaction of 4a-adduct I with a sulfane sulfur acceptor (N:) generates 4a-adduct II and the thiolate form of Cys379 (step 3). Nucleophilic attack of Cys379S- at the sulfur atom in the 4a-adduct produces 1,5-dihydroFAD and regenerates the disulfide bridge (step 4). The catalytic cycle is completed upon transfer of electrons from 1,5-dihydro-FAD to CoQ Homo sapiens
a

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
hydrogen sulfide + glutathione + coenzyme Q
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 Homo sapiens S-sulfanylglutathione + reduced coenzyme Q
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 ir
additional information CoQ-binding pocket and substrate binding structures, overview. The entrance to the CoQ-binding pocket is located on the membrane-facing surface of human SQOR Homo sapiens ?
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Subunits

Subunits Comment Organism
More human SQOR comprises two tandem Rossmann fold domains and a C-terminal domain containing two helices (denoted the C-terminal and penultimate C-terminal helices). FAD is noncovalently bound in an extended conformation and is in the oxidized state. The first Rossmann fold starts near the N-terminus and binds the ADP portion of FAD. The second Rossmann fold is closer to the isoalloxazine ring of FAD but is mostly positioned at least 10 A away from the flavin ring with one notable exception. SQOR quaternary structure, detailed overview Homo sapiens

Synonyms

Synonyms Comment Organism
SQOR
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 Homo sapiens
sulfide:quinone oxidoreductase
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 Homo sapiens

Cofactor

Cofactor Comment Organism Structure
coenzyme Q
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 Homo sapiens
FAD required, FAD is noncovalently bound in an extended conformation and is in the oxidized state. The first Rossmann fold starts near the N-terminus and binds the ADP portion of FAD. The second Rossmann fold is closer to the isoalloxazine ring of FAD but is mostly positioned at least 10 A away from the flavin ring with one notable exception. FAD is bound in an extended conformation. Its interactions with the protein include 12 hydrogen bonds and electrostatic interactions with two helix dipoles. Two basic residues, Lys207 and Lys418, lie above the flavin's re- and si-face, respectively with their respective epsilon-amino groups 3.2 and 3.3 A from a carbonyl oxygen in the isoalloxazine ring (O4). Binding site structure, overview Homo sapiens

General Information

General Information Comment Organism
evolution human SQOR belongs to a family of flavoprotein disulfide reductases (FDR), members of which contain a pair of redox-active cysteine residues that typically form a disulfide in the resting enzyme Homo sapiens
metabolism sulfide:quinone oxidoreductase (SQOR) catalyzes the first irreversible step in the mitochondrial metabolism of hydrogen sulfide (H2S). SQOR plays a major role in controlling physiological levels of H2S and sits at a key pharmacological intervention point Homo sapiens
additional information molecular basis for the enzyme's ability to catalyze sulfane sulfur transfer reactions with structurally diverse acceptors, molecular basis for the enzyme's ability to catalyze sulfane sulfur transfer reactions with structurally diverse acceptors, overview. Human SQOR contains unique features: an electro-positive surface depression implicated as a binding site for sulfane sulfur acceptors and postulated to funnel negatively charged substrates to a hydrophilic H2S-oxidizing active site, which is connected to a hydrophobic internal tunnel that binds coenzyme Q. The enzyme has a unique binding site for sulfane sulfur acceptors. The two active-site cysteine residues (Cys201, Cys379) lie just above the re-face of the flavin ring. In both the SeMet-substituted and native enzyme structures, these cysteine residues are linked by a bridging sulfur to form thiocystine (Cys-S-S-S-Cys). Structure-analysis relationship, overview. The two C-terminal helices lie in the plane of the mitochondrial membrane, with their hydrophobic faces communicating with the membrane interior. This monotopic mode of association allows the enzyme to gain access to its hydrophobic electron acceptor, CoQ. The position of the C-terminal helix is likely perturbed by a crystal contact with the penultimate helix in a symmetry-related molecule. Thus, the last residue in the C-terminal helix, Glu452, forms hydrogen bonds with residues (Arg411, Leu412, Ser413) in the penultimate helix of the adjacent chain Homo sapiens
physiological function SQOR plays a major role in controlling physiological levels of H2S. SQOR catalyzes a two-electron oxidation of H2S to sulfane sulfur (S0). It uses coenzyme Q (CoQ) as electron acceptor and sulfite or glutathione as sulfane sulfur acceptor in reactions that produce thiosulfate or glutathione persulfide (GSS-), respectively Homo sapiens