Role of tyrosine residue in methane activation at the dicopper site of particulate methane monooxygenase: A density functional theory study

Methane hydroxylation at the dinuclear copper site of particulate methane monooxygenase (pMMO) is studied by using density functional theory calculations. The electronic, structural, and reactivity properties of a possible dinuclear copper species (μ-oxo)(μ-hydroxo)Cu^IICu^III are discussed with respect to the C-H bond activation of methane. We propose that the tyrosine residue in the second coordination sphere of the dicopper site donates an H atom to the μ-η²:η²-peroxoCu ^IICu^II species and the resultant (μ-oxo)(μ-hydroxo) Cu^IICu^III species can hydroxylate methane. This species for methane hydroxylation is more favorable in reactivity than the bis(μ-oxo)Cu^IIICu^III species. The H-atom transfer or proton-coupled electron transfer from the tyrosine residue can reasonably induce the O-O bond dissociation of the μ-η²:η²- peroxoCu^IICu^II species to form the reactive (μ-oxo)(μ-hydroxo)Cu^IICu^III species, which is expected to be an active species for the conversion of methane to methanol at the dicopper site of pMMO. The rate-determining step for the methane hydroxylation is the C-H cleavage, which is in good agreement with experimental KIE values reported so far.