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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1gqg

E.C. namequercetin 2,3-dioxygenase
SpeciesAspergillus japonicus ()
E.C. Number (IntEnz) 1.13.11.24
CSA Homologues of 1gqgThere are 21 Homologs
CSA Entries With UniProtID Q7SIC2
CSA Entries With EC Number 1.13.11.24
PDBe Entry 1gqg
PDBSum Entry 1gqg
MACiE Entry 1gqg

Literature Report

IntroductionQuercetin 2,3-dioxygenase is a copper-dependent enzyme that catalyses the reaction of dioxygen with quercin (3,5,7,3',4'-pentahydroxy flavone). Dioxygenases are enzymes that catalyses the incorporation of both atoms of molecular oxygen into organic substrates, most notably during the degradation of aromatic compounds. They typically use a metal ion to circumvent the spin barrier that prevents the direct reaction of the triplet ground state of dioxygen with singlet-state organic compounds. In most of the well-studied dioxygenases, the metal used is iron; quercetin 2,3-dioxygenase is the only known member of this family to use copper.
MechansimQuercetin 2,3-dioxygenase uses a Cu(II) ion to avoid problems of spin associated with reactions involving dioxygen. In the first step, the C3 hydroxyl of the substrate coordinates the Cu(II) and transfers its proton to Glu 73. Dioxygen must now bind to this complex. The ground state [Cu(II)-substrate] binds dioxygen quite poorly, and the low-lying excited state [Cu(I)-substrate(radical)] is the acceptor instead. Recent theoretical calculations suggest that dioxygen binds to the Cu(I) of this state rather than to the substrate radical. The resulting dioxygen adduct (with three unpaired spins) is now well set up for attack by the peroxy radical on the C2 radical of the substrate, with formation of a C2-O bond.
Next, the peroxide oxygen attached to the copper forms a second C-O bond with C4, concurrent with breaking of the C4 carbonyl pi bond and bond formation between the C4 carbonyl oxygen and the copper. Glu 73 provides electrostatic stabilisation by shifting its hydrogen bond donation from the C3 substrate oxygen to the C4 substrate oxygen.
The bridging peroxide O-O bond is now cleaved, with simultaneous cleavage of the C3-C2 and C3-C4 bonds to release C3 as carbon monoxide and form a new ketone at C2 and carboxylate (still coordinated to copper) at C4. Finally, the proton stored on Glu 73 is transferred to the C4 carboxylate, and the product then leaves.
Reaction

Catalytic Sites for 1gqg

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluA7373macie:sideChainAccepts proton from C3 hydroxyl of substrate. Acts as a hydrogen bond donor to the C3 and later the C4 substrate oxygens.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluB7373macie:sideChainAccepts proton from C3 hydroxyl of substrate. Acts as a hydrogen bond donor to the C3 and later the C4 substrate oxygens.

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluC7373macie:sideChainAccepts proton from C3 hydroxyl of substrate. Acts as a hydrogen bond donor to the C3 and later the C4 substrate oxygens.

Annotated By Reference To The Literature - Site 4 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluD7373macie:sideChainAccepts proton from C3 hydroxyl of substrate. Acts as a hydrogen bond donor to the C3 and later the C4 substrate oxygens.

Literature References

Notes:
Steiner RA
Functional analysis of the copper-dependent quercetin 2,3-dioxygenase. 1. Ligand-induced coordination changes probed by X-ray crystallography: inhibition, ordering effect, and mechanistic insights.
Biochemistry 2002 41 7955-7962
PubMed: 12069585
Siegbahn PE.
Hybrid DFT study of the mechanism of quercetin 2,3-dioxygenase.
Inorg Chem 2004 43 5944-5953
PubMed: 15360243
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