3NVY

Crystal Structure of Bovine Xanthine Oxidase in Complex with Quercetin

Summary for 3NVY

• Entry DOI: 10.2210/pdb3nvy/pdb
• Related: 3NVV 3NVW 3NVZ
• Descriptor: Xanthine dehydrogenase/oxidase, FE2/S2 (INORGANIC) CLUSTER, FLAVIN-ADENINE DINUCLEOTIDE, ... (9 entities in total)
• Functional Keywords: hydroxylase, homodimer, xanthine oxidase, quercetin, oxidoreductase
• Biological source: Bos taurus (bovine,cow,domestic cattle,domestic cow); More
• Cellular location: Cytoplasm (By similarity): P80457 P80457 P80457
• Total number of polymer chains: 6
• Total formula weight: 281051.13

Authors

Cao, H.,Hille, R. (deposition date: 2010-07-08, release date: 2011-01-19, Last modification date: 2024-02-21)

Primary citation

Cao, H.,Pauff, J.M.,Hille, R.
X-ray Crystal Structure of a Xanthine Oxidase Complex with the Flavonoid Inhibitor Quercetin.
J Nat Prod, 77:1693-1699, 2014

PubMed Abstract: Xanthine oxidase catalyzes the sequential hydroxylation of hypoxanthine to uric acid via xanthine as intermediate. Deposition of crystals of the catalytic product uric acid or its monosodium salt in human joints with accompanying joint inflammation is the major cause of gout. Natural flavonoids are attractive leads for rational design of preventive and therapeutic xanthine oxidase inhibitors due to their beneficial antioxidant, anti-inflammatory, and antiproliferative activities in addition to their micromolar inhibitory activities toward xanthine oxidase. We determined the first complex X-ray structure of mammalian xanthine oxidase with the natural flavonoid inhibitor quercetin at 2.0 Å resolution. The inhibitor adopts a single orientation with its benzopyran moiety sandwiched between Phe 914 and Phe 1009 and ring B pointing toward the solvent channel leading to the molybdenum active center. The favorable steric complementarity of the conjugated three-ring structure of quercetin with the active site and specific hydrogen-bonding interactions of exocyclic hydroxy groups with catalytically relevant residues Arg 880 and Glu 802 correlate well with a previously reported structure-activity relationship of flavonoid inhibitors of xanthine oxidase. The current complex provides a structural basis for the rational design of flavonoid-type inhibitors against xanthine oxidase useful for the treatment of hyperuricemia, gout, and inflammatory disease states.

PubMed: 25060641
DOI: 10.1021/np500320g

Experimental method

X-RAY DIFFRACTION (2 Å)