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

Molecular oxygen (O ) is a sustainable oxidation reagent. O is strongly oxidizing but kinetically stable and its final reaction product is water. For these reasons learning how to activate O and how to steer its reactivity along desired reaction pathways is a longstanding challenge in chemical research.

Structure of formylglycine-generating enzyme in complex with copper and a substrate reveals an acidic pocket for binding and activation of molecular oxygen.

The formylglycine generating enzyme (FGE) catalyzes oxidative conversion of specific peptidyl-cysteine residues to formylglycine. FGE mediates O-activation and hydrogen-atom abstraction in an active site that contains Cu(i) coordinated to two cysteine residues. Similar coordination geometries are common among copper-sensing transcription factors and copper-chaperone but are unprecedented among copper-dependent oxidases.