Expression, localization, structural, and functional characterization of pFGE, the paralog of the Cα-formylglycine-generating enzyme

Abstract

pFGE is the paralog of the formylglycine-generating enzyme (FGE), which, catalyzes the oxidation of a specific cysteine to Cα-formylglycine, the catalytic residue in the active site of sulfafases. 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 reticuhnn 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. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.