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

Abstract

Molecular oxygen (O₂ ) is a sustainable oxidation reagent. O₂ is strongly oxidizing but kinetically stable and its final reaction product is water. For these reasons learning how to activate O₂ and how to steer its reactivity along desired reaction pathways is a longstanding challenge in chemical research.^[1] Activation of ground-state diradical O₂ can occur either via conversion to singlet oxygen or by one-electron reduction to superoxide. Many enzymes facilitate activation of O₂ 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 O₂ juxtaposed, but not coordinated to the catalytic Cu^I . Isostructural complexes that contain Ag^I instead of Cu^I or nitric oxide instead of O₂ 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 O₂ is unprecedented for metal-dependent oxidases, but is reminiscent of flavin-dependent enzymes.