Generation of formylglycine residues in sulfatases

The active site of eukaryotic sulfatases carries an aldehyde group, which is posttranslationally generated by oxidation of a specific cysteine residue. The resulting C(alpha)-formylglycine residue (FGly) is the crucial functional group in the cleavage of the sulfate ester bond. Conversion of cysteine to FGly is catalyzed by an ER-resident enzyme called formylglycine-generating enzyme (FGE). Genetic defects of FGE lead to the synthesis of catalytically inactive sulfatase polypeptides, the cause of a rare but fatal lysosomal storage disorder called Multiple Sulfatase Deficiency. Currently we are analyzing the structure and the catalytic mechanism of FGE and the structurally related protein pFGE.