Dhamale Omkar P, Lawrence Roger, Wiegmann Elena M, Shah Bhahwal A, Al-Mafraji Kanar, Lamanna William C, Lübke Torben, Dierks Thomas, Boons Geert-Jan, Esko Jeffrey D
Complex Carbohydrate Research Center, University of Georgia , Athens, Georgia, United States.
Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego , La Jolla, California, United States.
ACS Chem Biol. 2017 Feb 17;12(2):367-373. doi: 10.1021/acschembio.6b01033. Epub 2017 Jan 17.
The degradation of glycosaminoglycans (GAGs) involves a series of exolytic glycosidases and sulfatases that act sequentially on the nonreducing end of the polysaccharide chain. Enzymes have been cloned that catalyze all of the known linkages with the exception of the removal of the 2-O-sulfate group from 2-sulfoglucuronate, which is found in heparan sulfate and dermatan sulfate. Here, we show using synthetic disaccharide substrates that arylsulfatase K is the glucuronate-2-sulfatase. Arylsulfatase K acts selectively on 2-sulfoglucuronate and lacks activity against 2-sulfoiduronate, whereas iduronate-2-sulfatase (IDS) desulfates synthetic disaccharides containing 2-sulfoiduronate but not 2-sulfoglucuronate. As arylsulfatase K has all of the properties expected of a lysosomal enzyme, we conclude that arylsulfatase K is the long sought lysosomal glucuronate-2-sulfatase, which we designate GDS.
糖胺聚糖（GAGs）的降解涉及一系列外切糖苷酶和硫酸酯酶，它们依次作用于多糖链的非还原端。除了从硫酸乙酰肝素和硫酸皮肤素中存在的2-硫酸葡糖醛酸中去除2-O-硫酸基团外，催化所有已知连接的酶已被克隆。在这里，我们使用合成二糖底物表明芳基硫酸酯酶K是葡糖醛酸-2-硫酸酯酶。芳基硫酸酯酶K选择性地作用于2-硫酸葡糖醛酸，对2-硫酸艾杜糖醛酸没有活性，而艾杜糖醛酸-2-硫酸酯酶（IDS）使含有2-硫酸艾杜糖醛酸而非2-硫酸葡糖醛酸的合成二糖脱硫。由于芳基硫酸酯酶K具有溶酶体酶所期望的所有特性，我们得出结论，芳基硫酸酯酶K是长期寻找的溶酶体葡糖醛酸-2-硫酸酯酶，我们将其命名为GDS。
