Abstract
pFGE is the paralog of the formylglycine-generating enzyme (FGE), which catalyzes the oxidation of a specific cysteine to Calpha-formylglycine, the catalytic residue in the active site of sulfatases. The enzymatic activity of sulfatases depends on this posttranslational modification, and the genetic defect of FGE causes multiple sulfatase deficiency. The structural and functional properties of pFGE were analyzed. The comparison with FGE demonstrates that both share a tissue-specific expression pattern and the localization in the lumen of the endoplasmic reticulum. Both are retained in the endoplasmic reticulum by a saturable mechanism. Limited proteolytic cleavage at similar sites indicates that both also share a similar three-dimensional structure. pFGE, however, is lacking the formylglycine-generating activity of FGE. Although overexpression of FGE stimulates the generation of catalytically active sulfatases, overexpression of pFGE has an inhibitory effect. In vitro pFGE interacts with sulfatase-derived peptides but not with FGE. The inhibitory effect of pFGE on the generation of active sulfatases may therefore be caused by a competition of pFGE and FGE for newly synthesized sulfatase polypeptides.
Highlights
The catalytic site of pro- and eukaryotic sulfatases contains a unique amino acid, C␣-formylglycine (FGly)1 [1,2,3,4,5,6,7,8,9]
Characterization of Recombinant paralog of FGE (pFGE)—pFGE with a Cterminal HA tag was transiently expressed in the human HT1080 sarcoma cell line. pFGE colocalized with protein disulfide isomerase, a lumenal protein of the endoplasmic reticulum (Fig. 2, A–C)
Immunoelectronmicroscopy confirmed the localization of pFGE in the endoplasmic reticulum, where it colocalizes with protein disulfide isomerase (Fig. 3A) and in the Golgi stack (Fig. 3B)
Summary
The catalytic site of pro- and eukaryotic sulfatases contains a unique amino acid, C␣-formylglycine (FGly)1 [1,2,3,4,5,6,7,8,9]. PFGE is the paralog of the formylglycine-generating enzyme (FGE), which catalyzes the oxidation of a specific cysteine to C␣-formylglycine, the catalytic residue in the active site of sulfatases. Overexpression of FGE stimulates the generation of catalytically active sulfatases, overexpression of pFGE has an inhibitory effect.
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