This domain is found in eukaryotic proteins [1] required for post-translational sulfatase modification (SUMF1). These proteins are associated with the rare disorder multiple sulfatase deficiency (MSD) [2]. The protein product of the SUMF1 gene is FG ...
This domain is found in eukaryotic proteins [1] required for post-translational sulfatase modification (SUMF1). These proteins are associated with the rare disorder multiple sulfatase deficiency (MSD) [2]. The protein product of the SUMF1 gene is FGE, formylglycine (FGly),-generating enzyme, which is a sulfatase. Sulfatases are enzymes essential for degradation and remodelling of sulfate esters, and formylglycine (FGly), the key catalytic in the active site, is unique to sulfatases [3]. FGE is localised to the endoplasmic reticulum (ER) and interacts with and modifies the unfolded form of newly synthesised sulfatases. FGE is a single-domain monomer with a surprising paucity of secondary structure that adopts a unique fold which is stabilised by two Ca2+ ions. The effect of all mutations found in MSD patients is explained by the FGE structure, providing a molecular basis for MSD. A redox-active disulfide bond is present in the active site of FGE. An oxidised cysteine residue, possibly cysteine sulfenic acid, has been detected that may allow formulation of a structure-based mechanism for FGly formation from cysteine residues in all sulfatases [4]. In Mycobacteria and Treponema denticola this enzyme functions as an iron(II)-dependent oxidoreductase [5,6].
