PDBsum entry 1h1i

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chains
344 a.a. *
NAG ×14
QUE ×4
MPD ×4
_CU ×4
Waters ×1539
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Crystal structure of quercetin 2,3-dioxygenase anaerobically complexed with the substrate quercetn
Structure: Quercetin 2,3-dioxygenase. Chain: a, b, c, d. Engineered: yes
Source: Aspergillus japonicus. Organism_taxid: 34381. Expressed in: aspergillus awamori. Expression_system_taxid: 105351
Biol. unit: Dimer (from PDB file)
1.75Å     R-factor:   0.150     R-free:   0.183
Authors: R.A.Steiner,B.W.Dijkstra
Key ref:
R.A.Steiner et al. (2002). Anaerobic enzyme.substrate structures provide insight into the reaction mechanism of the copper-dependent quercetin 2,3-dioxygenase. Proc Natl Acad Sci U S A, 99, 16625-16630. PubMed id: 12486225 DOI: 10.1073/pnas.262506299
15-Jul-02     Release date:   28-Nov-02    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q7SIC2  (QDOI_ASPJA) -  Quercetin 2,3-dioxygenase
350 a.a.
344 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Quercetin 2,3-dioxygenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Quercetin 2,3-Dioxygenase
      Reaction: Quercetin + O2 = 2-(3,4-dihydroxybenzoyloxy)-4,6-dihydroxybenzoate + CO + H+
Bound ligand (Het Group name = QUE)
corresponds exactly
+ O(2)
= 2-(3,4-dihydroxybenzoyloxy)-4,6-dihydroxybenzoate
+ CO
+ H(+)
      Cofactor: Iron or copper
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   1 term 
  Biochemical function     oxidoreductase activity     4 terms  


DOI no: 10.1073/pnas.262506299 Proc Natl Acad Sci U S A 99:16625-16630 (2002)
PubMed id: 12486225  
Anaerobic enzyme.substrate structures provide insight into the reaction mechanism of the copper-dependent quercetin 2,3-dioxygenase.
R.A.Steiner, K.H.Kalk, B.W.Dijkstra.
Quercetin 2,3-dioxygenase (2,3QD) is the only firmly established copper dioxygenase known so far. Depending solely on a mononuclear Cu center, it catalyzes the breakage of the O-heterocycle of flavonols, producing more easily degradable phenolic carboxylic acid ester derivatives. In the enzymatic process, two CC bonds are broken and concomitantly carbon monoxide is released. The x-ray structures of Aspergillus japonicus 2,3QD anaerobically complexed with the substrate kaempferol and the natural substrate quercetin have been determined at 1.90- and 1.75-A resolution, respectively. Flavonols coordinate to the copper ion as monodentate ligands through their 3OH group. They occupy a shallow and overall hydrophobic cavity proximal to the metal center. As a result of a van der Waals contact between the most outward flavonol A-ring and Pro(164), a flexible loop in front of the active site becomes partly ordered. Interestingly, flavonols bound to 2,3QD are bent at the C2 atom, which is pyramidalized. The increased local sp(3) character at this atom may stabilize a carbon-centered radical activated for dioxygen attack. Glu(73) coordinates the copper through its O epsilon 1 atom. The short distance of about 2.55 A between its O epsilon 2 atom and the flavonol O3 atom suggests that a hydrogen bond exists between the two atoms, indicating that Glu(73) can act as a base in flavonol deprotonation and that it retains the proton. Structure-based geometric considerations indicate O(2) binding to the flavonol C2 atom as the preferred route for flavonol dioxygenation.
  Selected figure(s)  
Figure 3.
Fig. 3. (A) Lateral view of the substrate QUE in 2,3QD o QUE (molecule A). Simulated annealing omit F[o]-F[c] electron density (43), calculated with the program CNX (Accelrys), is contoured at the 3.0 level. In both crystallographically determined E o S complexes, the substrates evidence a pyramidalization of the C2 atom. (B) Side view of the catalytic center of 2,3QD o KMP. The copper coordination is best defined as square pyramidal, with His68 as apical ligand. Phe^75, Phe^114, Val63, His66, and His112 define a cavity available for the dioxygen molecule. Simulated annealing omit F[o]-F[c] electron density is contoured at the 3.0 level.
Figure 4.
Fig. 4. Proposed reaction mechanism for 2,3QD-mediated dioxygenation of flavonols.
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20460727 K.Hirooka, and Y.Fujita (2010).
Excess production of Bacillus subtilis quercetin 2,3-dioxygenase affects cell viability in the presence of quercetin.
  Biosci Biotechnol Biochem, 74, 1030-1038.  
20559823 M.Morikawa (2010).
Dioxygen activation responsible for oxidation of aliphatic and aromatic hydrocarbon compounds: current state and variants.
  Appl Microbiol Biotechnol, 87, 1595-1603.  
20080731 R.A.Steiner, H.J.Janssen, P.Roversi, A.J.Oakley, and S.Fetzner (2010).
Structural basis for cofactor-independent dioxygenation of N-heteroaromatic compounds at the alpha/beta-hydrolase fold.
  Proc Natl Acad Sci U S A, 107, 657-662.
PDB codes: 2wj3 2wj4 2wj6 2wm2 3ibt
20559499 S.Aparicio (2010).
A systematic computational study on flavonoids.
  Int J Mol Sci, 11, 2017-2038.  
20419500 S.Tranchimand, P.Brouant, and G.Iacazio (2010).
The rutin catabolic pathway with special emphasis on quercetinase.
  Biodegradation, 21, 833-859.  
19478949 G.Agarwal, M.Rajavel, B.Gopal, and N.Srinivasan (2009).
Structure-based phylogeny as a diagnostic for functional characterization of proteins with a cupin fold.
  PLoS One, 4, e5736.  
19521631 G.Baráth, J.Kaizer, G.Speier, L.Párkányi, E.Kuzmann, and A.Vértes (2009).
One metal-two pathways to the carboxylate-enhanced, iron-containing quercetinase mimics.
  Chem Commun (Camb), (), 3630-3632.  
19754880 S.Leitgeb, G.D.Straganz, and B.Nidetzky (2009).
Functional characterization of an orphan cupin protein from Burkholderia xenovorans reveals a mononuclear nonheme Fe2+-dependent oxygenase that cleaves beta-diketones.
  FEBS J, 276, 5983-5997.  
18502867 M.J.Moonen, S.A.Synowsky, W.A.van den Berg, A.H.Westphal, A.J.Heck, R.H.van den Heuvel, M.W.Fraaije, and W.J.van Berkel (2008).
Hydroquinone dioxygenase from pseudomonas fluorescens ACB: a novel member of the family of nonheme-iron(II)-dependent dioxygenases.
  J Bacteriol, 190, 5199-5209.  
17516049 H.Merkens, S.Sielker, K.Rose, and S.Fetzner (2007).
A new monocupin quercetinase of Streptomyces sp. FLA: identification and heterologous expression of the queD gene and activity of the recombinant enzyme towards different flavonols.
  Arch Microbiol, 187, 475-487.  
17701137 J.Lättig, M.Böhl, P.Fischer, S.Tischer, C.Tietböhl, M.Menschikowski, H.O.Gutzeit, P.Metz, and M.T.Pisabarro (2007).
Mechanism of inhibition of human secretory phospholipase A2 by flavonoids: rationale for lead design.
  J Comput Aided Mol Des, 21, 473-483.  
17698806 J.R.Gledhill, M.G.Montgomery, A.G.Leslie, and J.E.Walker (2007).
Mechanism of inhibition of bovine F1-ATPase by resveratrol and related polyphenols.
  Proc Natl Acad Sci U S A, 104, 13632-13637.
PDB codes: 2jiz 2jj1 2jj2
17639604 M.A.Adams, M.D.Suits, J.Zheng, and Z.Jia (2007).
Piecing together the structure-function puzzle: experiences in structure-based functional annotation of hypothetical proteins.
  Proteomics, 7, 2920-2932.  
  17565176 R.A.Steiner, U.Frerichs-Deeken, and S.Fetzner (2007).
Crystallization and preliminary X-ray analysis of 1H-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase from Arthrobacter nitroguajacolicus Rü61a: a cofactor-devoid dioxygenase of the alpha/beta-hydrolase-fold superfamily.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 382-385.  
17373707 S.Fiorucci, J.Golebiowski, D.Cabrol-Bass, and S.Antonczak (2007).
Molecular simulations bring new insights into flavonoid/quercetinase interaction modes.
  Proteins, 67, 961-970.  
16858718 G.D.Straganz, and B.Nidetzky (2006).
Variations of the 2-His-1-carboxylate theme in mononuclear non-heme FeII oxygenases.
  Chembiochem, 7, 1536-1548.  
16492780 J.G.McCoy, L.J.Bailey, E.Bitto, C.A.Bingman, D.J.Aceti, B.G.Fox, and G.N.Phillips (2006).
Structure and mechanism of mouse cysteine dioxygenase.
  Proc Natl Acad Sci U S A, 103, 3084-3089.
PDB code: 2atf
17119644 R.Bentley (2006).
From miso, saké and shoyu to cosmetics: a century of science for kojic acid.
  Nat Prod Rep, 23, 1046-1062.  
16786599 S.Fiorucci, J.Golebiowski, D.Cabrol-Bass, and S.Antonczak (2006).
Molecular simulations reveal a new entry site in quercetin 2,3-dioxygenase. A pathway for dioxygen?
  Proteins, 64, 845-850.  
16077096 A.Teplyakov, G.Obmolova, J.Toedt, M.Y.Galperin, and G.L.Gilliland (2005).
Crystal structure of the bacterial YhcH protein indicates a role in sialic acid catabolism.
  J Bacteriol, 187, 5520-5527.
PDB code: 1s4c
15778971 D.G.Covell, A.Wallqvist, R.Huang, N.Thanki, A.A.Rabow, and X.J.Lu (2005).
Linking tumor cell cytotoxicity to mechanism of drug action: an integrated analysis of gene expression, small-molecule screening and structural databases.
  Proteins, 59, 403-433.  
14645093 M.Fittipaldi, R.A.Steiner, M.Matsushita, B.W.Dijkstra, E.J.Groenen, and M.Huber (2003).
Single-crystal EPR study at 95 GHz of the type 2 copper site of the inhibitor-bound quercetin 2,3-dioxygenase.
  Biophys J, 85, 4047-4054.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.