Arylsulfatase K is the Lysosomal 2-Sulfoglucuronate Sulfatase.

Arylsulfatase K is the Lysosomal 2-Sulfoglucuronate Sulfatase.
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DOI:
10.1021/acschembio.6b01033
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发表时间:
2017-02-17
影响因子:
4
通讯作者:
Esko JD
Esko JD
中科院分区:
生物学2区
文献类型:
--
作者:
Dhamale OP;Lawrence R;Wiegmann EM;Shah BA;Al-Mafraji K;Lamanna WC;Lübke T;Dierks T;Boons GJ;Esko JD

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糖胺聚糖(GAG)的降解涉及一系列胞外糖苷酶和硫酸酯酶,它们依次作用于多糖链的非还原端。已经克隆了催化所有已知键的酶,除了从2-磺基葡糖醛酸酯中除去2-O-硫酸酯基团,这在硫酸乙酰肝素和硫酸皮肤素中发现。在这里,我们使用合成二糖底物,芳基硫酸酯酶K是葡萄糖醛酸-2-硫酸酯酶。芳基硫酸酯酶K选择性地作用于2-磺基葡糖醛酸,并且缺乏针对2-磺基艾杜糖醛酸的活性,而艾杜糖醛酸-2-硫酸酯酶(IDS)水解含有2-磺基艾杜糖醛酸但不含2-磺基葡糖醛酸的合成二糖。由于芳基硫酸酯酶K具有溶酶体酶的所有预期性质,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。
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.
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