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Zusammenfassung

The determination of the diiron core intermediate structures involved in the catalytic cycle of soluble methane monooxygenase (sMMO), the enzyme that selectively catalyzes the conversion of methane to methanol, has been a subject of intense interest within the bioinorganic scientific community. Particularly, the specific geometry and electronic structure of the intermediate that precedes methane binding, known as intermediate Q (or MMOH_Q), has been debated for over 30 years. Some reported studies support a bis-μ-oxo-bridged Fe(IV)₂O₂ closed-core conformation Fe(IV)₂O₂ core, whereas others favor an open-core geometry, with a longer Fe–Fe distance. The lack of consensus calls for a thorough re-examination and reinterpretation of the spectroscopic data available on the MMOH_Q intermediate. Herein, we report extensive simulations based on a hybrid quantum mechanics/molecular mechanics approach (QM/MM) approach that takes into account the complete enzyme to explore possible conformations for intermediates MMOH_ox and MMOH_Q of the sMMOH catalytic cycle. High-level quantum chemical approaches are used to correlate specific structural motifs with geometric parameters for comparison with crystallographic and EXAFS data, as well as with spectroscopic data from Mössbauer spectroscopy, Fe K-edge high-energy resolution X-ray absorption spectroscopy (HERFD XAS), and resonance Raman ¹⁶O–¹⁸O difference spectroscopy. The results provide strong support for an open-core-type configuration in MMOH_Q, with the most likely topology involving mono-oxo-bridged Fe ions and alternate terminal Fe-oxo and Fe-hydroxo groups that interact via intramolecular hydrogen bonding. The implications of an open-core intermediate Q on the reaction mechanism of sMMO are discussed.