Copper is a versatile catalyst for the transfer of electrons from organic matter to molecular oxygen. Some copper-oxygen adducts can cleave very strong C-H bonds. Understanding the nature of these catalytic species is a major scientific objective and allows controlling their specific activities by proteins or synthetic ligands. Mononuclear copper enzymes are a particularly promising class of such catalysts. The formylglycine generating enzyme (FGE) as a novel type of copper-dependent oxidase participates in activation of pro- and eukaryotic sulfatases by converting specific Cys residue into formylglycine (fGly) [1].

The proposed catalytic cycle of FGE T. curvata involves the stereo selective C-H bond abstraction as the rate limiting step that was proved by significant KIE = 3.7 ± 0.1 [2]. Recent structural and kinetic evidences identify that Cu(I), bounded to two Cys in the active site of FGE, plays a role of redox cofactor [3].  

In this presentation, we will discuss our recent efforts in deciphering the catalytic mechanism of this enzyme.

[1] Jens Fey, et al., J Biol Chem, 2001, 276(50), 47021-8.
[2] Matthias Knop, et al., Chembiochem, 2015, 16(15), 2147-50.
[3] Matthias Knop, et al., Chembiochem, 2017, 18(2), 161-165.