title: Computational Study of Catalytic Reaction of Quercetin 2,4-Dioxygenase.
abstract: We present a quantum mechanics/molecular mechanics (QM/MM) and QM-only study on the oxidative ring-cleaving reaction of quercetin catalyzed by quercetin 2,4-dioxygenase (2,4-QD). 2,4-QD has a mononuclear type 2 copper center and incorporates two oxygen atoms at C2 and C4 positions of the substrate. It has not been clear whether dioxygen reacts with a copper ion or a substrate radical as the first step. We have found that dioxygen is more likely to bind to a Cu(2+) ion, involving the dissociation of the substrate from the copper ion. Then a Cu(2+)-alkylperoxo complex can be generated. Comparison of geometry and stability between QM-only and QM/MM results strongly indicates that steric effects of the protein environment contribute to maintain the orientation of the substrate dissociated from the copper center. The present QM/MM results also highlight that a prior rearrangement of the Cu(2+)-alkylperoxo complex and a subsequent hydrogen bond switching assisted by the movement of Glu73 can facilitate formation of an endoperoxide intermediate selectively.
authors.affiliation: †Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan.|‡Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology (JST) Agency, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Saito
authors.affiliation: †Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawakami
authors.affiliation: †Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan.|‡Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology (JST) Agency, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Shusuke
authors.initials: S
authors.lastname: Yamanaka
authors.affiliation: †Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan.|‡Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology (JST) Agency, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Okumura
mesh_terms: D002384:Catalysis; D002413:Cations, Divalent / Q000737:chemistry; D003300:Copper / Q000737:chemistry; D049308:Dioxygenases / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010100:Oxygen / Q000737:chemistry; D011789:Quantum Theory; D011794:Quercetin / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D002413:Cations, Divalent; D014867:Water; D003300:Copper; D011794:Quercetin; D049308:Dioxygenases; D010100:Oxygen