title: Insights into the (superoxo)Fe(III)Fe(III) intermediate and reaction mechanism of myo-inositol oxygenase: DFT and ONIOM(DFT:MM) study.
abstract: The (superoxo)Fe(III)Fe(III) reactive species and the catalytic reaction mechanism of a diiron enzyme, myo-inositol oxygenase (MIOX), were theoretically investigated by means of density functional theory (DFT) and ONIOM quantum mechanical/molecular mechanical (QM/MM) approaches. The ground state of the (superoxo)Fe(III)Fe(III) intermediate was shown to have a side-on coordination geometry and an S = 1/2 spin state, wherein the two iron sites are antiferromagnetically coupled while the superoxide site and the nearest iron are ferromagnetically coupled. A full reaction pathway leading to a D-glucuronate product from myo-inositol was proposed based on ONIOM computational results. Two major roles of the enzyme surrounding during the catalytic reaction were identified. One is to facilitate the initial H-abstraction step, and the other is to restrict the movement of the substrate via H-bonding interactions in order to avoid unwanted side reactions. In our proposed mechanism, O-O bond cleavage has the highest barrier, thus constituting the rate-limiting step of the reaction. The unique role of the bridging hydroxide ligand as a catalytic base was also identified.
authors.affiliation: Fukui Institute for Fundamental Chemistry, Kyoto University, 34-4 Takano Nishihiraki-cho, Sakyo, Kyoto 606-8103, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Hirao
authors.forename: Keiji
authors.initials: K
authors.lastname: Morokuma
mesh_terms: D005290:Ferric Compounds / Q000737:chemistry*; D050562:Inositol Oxygenase / Q000737:chemistry*; D008958:Models, Molecular; D011789:Quantum Theory
chemical_list: D005290:Ferric Compounds; D050562:Inositol Oxygenase