Crystal Structure of the Copper-Containing Quercetin 2,3-Dioxygenase from Aspergillus japonicus

• Published in: Structure (London) Vol. 10; no. 2; pp. 259 - 268
• Main Authors: Fusetti, Fabrizia, Schröter, Klaus H, Steiner, Roberto A, van Noort, Paula I, Pijning, Tjaard, Rozeboom, Henriëtte J, Kalk, Kor H, Egmond, Maarten R, Dijkstra, Bauke W
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2002
• Subjects: Amino Acid Sequence; Aspergillus - enzymology; Binding Sites; copper; Copper - metabolism; Crystallography, X-Ray; cupin; dioxygenase; Dioxygenases; glycoprotein; Glycosylation; Models, Molecular; Molecular Sequence Data; Oxygenases - chemistry; Oxygenases - metabolism; Protein Structure, Quaternary; Protein Structure, Tertiary; quercetin; Sequence Alignment; Static Electricity; Substrate Specificity; X-ray structure; dioxygenase; copper; quercetin; cupin; glycoprotein; X-ray structure
• ISSN: 0969-2126; 1878-4186
• DOI: 10.1016/S0969-2126(02)00704-9

Quercetin 2,3-dioxygenase is a copper-containing enzyme that catalyzes the insertion of molecular oxygen into polyphenolic flavonols. Dioxygenation catalyzed by iron-containing enzymes has been studied extensively, but dioxygenases employing other metal cofactors are poorly understood. We determined the crystal structure of quercetin 2,3-dioxygenase at 1.6 Å resolution. The enzyme forms homodimers, which are stabilized by an N-linked heptasaccharide at the dimer interface. The mononuclear type 2 copper center displays two distinct geometries: a distorted tetrahedral coordination, formed by His66, His68, His112, and a water molecule, and a distorted trigonal bipyramidal environment, which additionally comprises Glu73. Manual docking of the substrate quercetin into the active site showed that the different geometries of the copper site might be of catalytic importance.