title: Quercetin 2,4-Dioxygenase Activates Dioxygen in a Side-On O2-Ni Complex.
abstract: Quercetin 2,4-dioxygenase (quercetinase) from Streptomyces uses nickel as the active-site cofactor to catalyze oxidative cleavage of the flavonol quercetin. How this unusual active-site metal supports catalysis and O2 activation is under debate. We present crystal structures of Ni-quercetinase in three different states, thus providing direct insight into how quercetin and O2 are activated at the Ni(2+) ion. The Ni(2+) ion is coordinated by three histidine residues and a glutamate residue (E(76)) in all three states. Upon binding, quercetin replaces one water ligand at Ni and is stabilized by a short hydrogen bond through E(76) , the carboxylate group of which rotates by 90°. This conformational change weakens the interaction between Ni and the remaining water ligand, thereby preparing a coordination site at Ni to bind O2. O2 binds side-on to the Ni(2+) ion and is perpendicular to the C2-C3 and C3-C4 bonds of quercetin, which are cleaved in the following reaction steps.
authors: Institut für Biologie, Strukturbiologie/Biochemie, Humboldt-Universität zu Berlin, Unter den Linden 6, 10099, Berlin, Germany.
authors: Jae-Hun
authors: JH
authors: Jeoung
authors: Institut für Molekulare Mikrobiologie und Biotechnologie, Westfälische Wilhelms-Universität Münster, 48149, Münster, Germany.
authors: Dimitrios
authors: D
authors: Nianios
authors: Institut für Molekulare Mikrobiologie und Biotechnologie, Westfälische Wilhelms-Universität Münster, 48149, Münster, Germany.
authors: Susanne
authors: S
authors: Fetzner
authors: Institut für Biologie, Strukturbiologie/Biochemie, Humboldt-Universität zu Berlin, Unter den Linden 6, 10099, Berlin, Germany. holger.dobbek@hu-berlin.de.
authors: Holger
authors: http://orcid.org/0000-0002-4122-3898
authors: H
authors: Dobbek
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D002384:Catalysis; D049308:Dioxygenases / Q000737:chemistry*; D015394:Molecular Structure; D009532:Nickel / Q000737:chemistry*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; D009532:Nickel; D049308:Dioxygenases; D010100:Oxygen
keywords: biocatalysis; carbon monoxide; dioxygen activation; dioxygenases; nickel superoxo complexes