Sulfatases belong to a highly conserved family of enzymes that catalyze the hydrolysis of O- and N-sulfate esters from a variety of substrates. About one third are found in lysosomes and serve to remove sulfate from glycosaminoglycans (GAGs), glycopeptides and glycolipids (GLs). The remaining are found in microsomes, endoplasmic reticulum (ER), Golgi, cell surface or secreted and active against hydroxysteroids, heparin or unidentified substrates. Genetic deficiencies of individual sulfatases reveal the critical importance of these enzymes in the metabolism of specific forms of sulfate. Deficiencies of lysosomal sulfatases that act on
GAGs and GLs account for the mucopolysaccharidoses (MPS) and metachromatic leukodystrophy, respectively. Deficiencies in non-lysosomal sulfatases, arylsulfases C and E, cause X-linked ichthyosis (XLI) and chondrodysplasia punctata (CDPX), respectively.
Mammalian sulfatases have a common CXPXR motif, in which the Cys residue is post-translationally modified to a Ca-formylglycine (FGly) residue. This modification is essential for catalytic activity of all sulfatases and is catalyzed by FGly generating enzyme (FGE) encoded by sulfatase modifying factor (SUMF). FGE deficiency is the reason for multiple sulfatase deficiency (MSD), a rare autosomal recessive disorder.
Sulfatase Modifying Factors
Sulfotransferase Assays and Substrates