Arylsulfatase

Arylsulfatases are a family of enzymes that catalyze the hydrolysis of sulfate esters from aryl substrates, releasing an alcohol and free sulfate. They act on a variety of substrates, including aryl sulfates, sulfate esters of steroids, and sulfated glycosaminoglycans, and play a key role in the degradation and remodeling of sulfated biomolecules in different organisms. Members of the family are found in bacteria, plants, fungi, and animals, and their cellular localization varies with function, ranging from lysosomes to periplasmic spaces.

Biochemically, arylsulfatases share a conserved sulfatase domain and rely on a catalytic formylglycine residue in the active site. This residue is generated post-translationally from a cysteine or serine by the formylglycine-generating enzyme (FGE). The formylglycine acts as the nucleophile that cleaves the sulfate ester, producing the corresponding alcohol and inorganic sulfate.

In humans, lysosomal arylsulfatases such as ARSA and ARSB participate in the breakdown of sulfated biomolecules. ARSA degrades sulfatides, while ARSB targets dermatan and chondroitin sulfates. Deficiencies in ARSA cause metachromatic leukodystrophy, characterized by sulfatide accumulation, and ARSB deficiency leads to mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome) with dermatan sulfate buildup. Other arylsulfatases, including ARSE, have roles in development, and mutations can be associated with skeletal disorders. The broader arylsulfatase family is thus essential for proper turnover of sulfated substrates.

Structurally, arylsulfatases typically harbor a single sulfatase domain and rely on the formylglycine cofactor for activity. They are encoded by multiple genes with diverse tissue distribution and subcellular localization, reflecting their varied physiological roles.

Applications of arylsulfatases include biochemical assays, investigation of sulfatase function in health and disease, and potential use in biotechnological desulfation processes and enzyme replacement strategies.