Mammalian Sulfatases: Biochemistry, Disease Manifestation, and Therapy

Abstract

Sulfatases are enzymes that catalyze the removal of sulfate from biological substances, an essential process for the homeostasis of the body. They are commonly activated by the unusual amino acid formylglycine, which is formed from cysteine at the catalytic center, mediated by a formylglycine-generating enzyme as a post-translational modification. Sulfatases are expressed in various cellular compartments such as the lysosome, the endoplasmic reticulum, and the Golgi apparatus. The substrates of mammalian sulfatases are sulfolipids, glycosaminoglycans, and steroid hormones. These enzymes maintain neuronal function in both the central and the peripheral nervous system, chondrogenesis and cartilage in the connective tissue, detoxification from xenobiotics and pharmacological compounds in the liver, steroid hormone inactivation in the placenta, and the proper regulation of skin humidification. Human sulfatases comprise 17 genes, 10 of which are involved in congenital disorders, including lysosomal storage disorders, while the function of the remaining seven is still unclear. As for the genes responsible for pathogenesis, therapeutic strategies have been developed. Enzyme replacement therapy with recombinant enzyme agents and gene therapy with therapeutic transgenes delivered by viral vectors are administered to patients. In this review, the biochemical substrates, disease manifestation, and therapy for sulfatases are summarized.

Keywords: biochemistry; formylglycine; gene therapy; post-translational modification; sulfatase.

Figure 1

Sulfatase and sulfotransferase. Sulfotransferase transfers a sulfate at the expense of PAPS at the specific position of lipids, cholesterol, and sugars. Sulfatase removes a sulfate from the substrate. Sulfatase needs to be activated by a formylglycine-generating enzyme, as described in the text. PAPS, 3′-phosphoadenosine 5′-phosphosulfate.