Density Functional Study on Possible Peroxo Form of Non-heme Diiron Enzyme Model

Abstract

Dioxygen binding to the active dinuclear iron site of methane monooxygenase (MMO) is theoretically analyzed with a density functional method. The μ-η1:η1-O2 mode was calculated to be the most favorable binding mode of dioxygen to a supposed active site of MMO that contains two five-coordinate irons(II).

Structure–Spectroscopy Correlations for Intermediate Q of Soluble Methane Monooxygenase: Insights from QM/MM Calculations

“…36,38,51 Here, a CH bond of the substrate is broken by a μ-oxo, leading to a CH 3 radical that rebounds with the same oxygen. Mechanism Va, advocated by the Yoshizawa group, [42][43][44][45][46][47][48][49]69 is best described as a concerted nonradical mechanism, initiated by a proton transfer to a μ-oxo while stabilizing the CH 3 group at the iron, before recombination to methanol. A variant of that mechanism was termed the nonsynchronous concerted pathway (Vb), explored by Friesner and Lippard.…”

“…This mechanism was suggested by Siegbahn and co-workers. ,, One could also imagine an oxygen centered variance of this mechanism, then termed the radical rebound mechanism: IVb . ,, Here, a CH bond of the substrate is broken by a μ-oxo, leading to a CH 3 radical that rebounds with the same oxygen. Mechanism Va , advocated by the Yoshizawa group, − , is best described as a concerted nonradical mechanism, initiated by a proton transfer to a μ-oxo while stabilizing the CH 3 group at the iron, before recombination to methanol. A variant of that mechanism was termed the nonsynchronous concerted pathway ( Vb ), explored by Friesner and Lippard. ,,, Here, the CH 3 group is stabilized by the protein environment, not the iron.…”

“…Computational studies of this system have a long history in assisting experimental interpretation and suggesting a possible mechanism. 1 9 , 2 1 , 2 3 , 3 5 − 6 9 Aside from structure predictions, 19,36,37,40,41,60 both the transition from MMOH P to MMOH Q 21,38,39,42,43,45,52,68 and the substrate oxidation 35,38,44,[46][47][48][49][50][51]53,54,[56][57][58][59][61][62][63][64][65]67,69 have been studied. However, most studies have been typically limited by the lack of extensive connections to spectroscopic data, in part because this information was not available at the time they were conducted.…”

“…This can be achieved through the development of computational models that correctly connect structural features of MMOH Q with the currently known spectroscopic observables. Computational studies of this system have a long history in assisting experimental interpretation and suggesting a possible mechanism. ,,,− Aside from structure predictions, ,,,,, both the transition from MMOH P to MMOH Q ,,,,,,, and the substrate oxidation ,,,− ,,,− ,− ,, have been studied. However, most studies have been typically limited by the lack of extensive connections to spectroscopic data, in part because this information was not available at the time they were conducted.…”

Protein effects on the O2 binding to the active site of the methane monooxygenase: ONIOM studies

“…Therefore, computational methods could be extremely useful in helping elucidate the reaction mechanism of methane monooxygenase. Indeed, ab initio and density functional theory (DFT) computational studies on various models of the reactive diiron center undertaken by various research groups 5, 18, 20, 23–52 allowed to gain new insight into the reaction mechanism. For example, as was found in our earlier computational studies 23 and later reaffirmed by Dunietz et al 5, methane oxidation by compound Q occurs through the “bound radical” mechanism.…”