Hybrid materials bearing organic and inorganic motives have been extensively discussed as playgrounds for the implementation of atomically resolved inorganic sites within a confined environment, with an exciting similarity to enzymes. Here, we present the successful design of a site-isolated mixed-metal Metal Organic Framework that mimics the reactivity of soluble methane monooxygenase enzyme reactivity and demonstrates the potential of this strategy to overcome current challenges in selective methane oxidation. We describe the synthesis and characterisation of an Fe-containing MOF that comprises the desired antiferromagnetically cou-pled high spin species in a coordination environment closely resembling that of the enzyme. An electrochemi-cal synthesis method is used to build the microporous MOF matrix while integrating, with an exquisite con-trol, the atomically dispersed Fe active sites in the crystalline scaffold. The model mimics the catalytic C-H activation behaviour of the enzyme to produce methanol, and shows that the key to this reactivity is the for-mation of isolated oxo-bridged Fe units.