Insights into the (superoxo)Fe(III)Fe(III) intermediate and reaction mechanism of myo-inositol oxygenase: DFT and ONIOM(DFT:MM) study

Journal of the American Chemical Society
Hajime Hirao, Keiji Morokuma

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.

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Citations

Aug 31, 2011·Journal of the American Chemical Society·Hajime Hirao, Keiji Morokuma
Nov 4, 2011·Journal of the American Chemical Society·Lung Wa ChungKeiji Morokuma
May 9, 2012·Journal of the American Chemical Society·Fern R McSorleyDavid L Zechel
Aug 2, 2011·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Hajime Hirao, Keiji Morokuma
May 28, 2016·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Tibor András RokobLubomír Rulíšek
Jul 2, 2016·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Nathalie Proos Vedin, Marcus Lundberg
Oct 28, 2016·Chemical Reviews·Geoff P Horsman, David L Zechel
Mar 3, 2017·Dalton Transactions : an International Journal of Inorganic Chemistry·Yafei JiangZongchao Jia
May 1, 2015·Chemical Science·Rong-Zhen Liao, Per E M Siegbahn
May 11, 2018·Physical Chemistry Chemical Physics : PCCP·Kai Xu, Hajime Hirao
Jul 7, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Henrique S FernandesNuno M F S A Cerqueira
Feb 14, 2021·International Journal of Molecular Sciences·Ilya Lyagin, Elena Efremenko
Apr 9, 2015·Chemical Reviews·Lung Wa ChungKeiji Morokuma
Mar 9, 2011·Journal of the American Chemical Society·John T WhitteckWilfred A van der Donk
Dec 26, 2013·Coordination Chemistry Reviews·Carsten KrebsJ Martin Bollinger

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