Non-Coordinative Binding of O2 at the Active Center of a Copper-Dependent Enzyme

Molecular oxygen (O-2) is a sustainable oxidation reagent. O-2 is strongly oxidizing but kinetically stable and its final reaction product is water. For these reasons learning how to activate O-2 and how to steer its reactivity along desired reaction pathways is a longstanding challenge in chemical research.([1]) Activation of ground-state diradical O-2 can occur either via conversion to singlet oxygen or by one-electron reduction to superoxide. Many enzymes facilitate activation of O-2 by direct fomation of a metal-oxygen coordination complex concomitant with inner sphere electron transfer. The formylglycine generating enzyme (FGE) is an unusual mononuclear copper enzyme that appears to follow a different strategy. Atomic-resolution crystal structures of the precatalytic complex of FGE demonstrate that this enzyme binds O-2 juxtaposed, but not coordinated to the catalytic Cu-I. Isostructural complexes that contain Ag-I instead of Cu-I or nitric oxide instead of O-2 confirm that formation of the initial oxygenated complex of FGE does not depend on redox activity. A stepwise mechanism that decouples binding and activation of O-2 is unprecedented for metal-dependent oxidases, but is reminiscent of flavin-dependent enzymes.

Automated summary

Molecular oxygen is a sustainable oxidation reagent with strong oxidizing properties and stability, ultimately forming water as the reaction product. The activation of O-2 can occur through various pathways, with enzymes typically forming metal-oxygen coordination complexes to facilitate the process. The formylglycine generating enzyme (FGE) demonstrates a unique strategy for activating O-2, involving binding of O-2 near, but not coordinated to, its catalytic copper atom.