Copper is a Cofactor of the Formylglycine‐Generating Enzyme

• Published in: Chembiochem : a European journal of chemical biology Vol. 18; no. 2; pp. 161 - 165
• Main Authors: Knop, Matthias, Dang, Thanh Quy, Jeschke, Gunnar, Seebeck, Florian P.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 17.01.2017; John Wiley and Sons Inc
• Subjects: Actinobacteria - enzymology; Biocatalysis; Catalytic Domain; Communication; Communications; copper; Copper - chemistry; Copper - metabolism; Cysteine - chemistry; Cysteine - metabolism; Electron Spin Resonance Spectroscopy; Enzymes; EPR; formylglycine; Glycine - analogs & derivatives; Glycine - chemistry; Glycine - metabolism; Humans; Kinetics; Molecular Dynamics Simulation; oxidases; oxygen activation; protein engineering; Sulfatases - chemistry; Sulfatases - metabolism; copper; protein engineering; EPR; oxygen activation; formylglycine; oxidases
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.201600359

Formylglycine‐generating enzyme (FGE) is an O2‐utilizing oxidase that converts specific cysteine residues of client proteins to formylglycine. We show that CuI is an integral cofactor of this enzyme and binds with high affinity (KD=of 10−17 m) to a pair of active‐site cysteines. These findings establish FGE as a novel type of copper enzyme. Biochemical characterization reveals the formylglycine‐generating enzyme as a copper‐dependent oxidase. The enzyme binds copper with attomolar affinity by using two active‐site cysteine residues as ligands. In the absence of reducing agent, the cysteine residues form a disulfide bond and the enzyme looses all metal affinity.