Publications

• Bacillus subtilis YxaG is a novel Fe-containing quercetin 2,3-dioxygenase.

  Bowater L., Fairhurst S.A., Just V.J., Bornemann S.

  The Bacillus subtilis genome contains genes for three hypothetical proteins belonging to the bicupin family, two of which we have previously shown to be Mn(II)-dependent oxalate decarboxylases. We have now shown that the third, YxaG, exhibits quercetin 2,3-dioxygenase activity and that it contains ... >> More

  The Bacillus subtilis genome contains genes for three hypothetical proteins belonging to the bicupin family, two of which we have previously shown to be Mn(II)-dependent oxalate decarboxylases. We have now shown that the third, YxaG, exhibits quercetin 2,3-dioxygenase activity and that it contains Fe ions. This contrasts with the eukaryotic enzyme which contains a Cu ion. YxaG is the first prokaryotic carbon monoxide-forming enzyme that utilises a flavonol to be characterised and is only the second example of a prokaryotic dioxygenolytic carbon monoxide-forming enzyme known to contain a cofactor. It is proposed to rename the B. subtilis gene qdoI. << Less

  FEBS Lett. 557:45-48(2004) [PubMed] [EuropePMC]

• Structural and biochemical analysis reveal pirins to possess quercetinase activity.

  Adams M., Jia Z.

  Pirin is a recently identified eukaryotic protein implicated in transcriptional activation and apoptosis. Homologues of Pirin are highly conserved in both prokaryotes and eukaryotes, but their function remains poorly understood. We present here the crystal structure of the yhhW gene product, a put ... >> More

  Pirin is a recently identified eukaryotic protein implicated in transcriptional activation and apoptosis. Homologues of Pirin are highly conserved in both prokaryotes and eukaryotes, but their function remains poorly understood. We present here the crystal structure of the yhhW gene product, a putative Pirin homologue, from Escherichia coli and confirm its structural similarity to Pirin. The YhhW protein displays a bicupin fold with a single N-terminal metal coordination site. Molecular surface comparisons of YhhW and Pirin with structurally similar proteins suggested quercetin as a potential ligand. We demonstrate that both bacterial and human Pirins have quercetinase activity, which is inhibited by the addition of typical inhibitors of the quercetin 2,3-dioxygenase reaction. We also demonstrate the release of carbon monoxide as a reaction product. This is the first report of enzymatic activity for any member of the Pirin family and may be an important connection to their roles in transcriptional regulation. << Less

  J. Biol. Chem. 280:28675-28682(2005) [PubMed] [EuropePMC]

• Quercetinase, a dioxygenase containing copper.

  Oka T., Simpson F.J.

  Biochem Biophys Res Commun 43:1-5(1971) [PubMed] [EuropePMC]

• Anaerobic enzyme.substrate structures provide insight into the reaction mechanism of the copper-dependent quercetin 2,3-dioxygenase.

  Steiner R.A., Kalk K.H., Dijkstra B.W.

  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 ... >> More

  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. << Less

  Proc. Natl. Acad. Sci. U.S.A. 99:16625-16630(2002) [PubMed] [EuropePMC]