2. Academic Validation
  3. Arylsulfatase K is the Lysosomal 2-Sulfoglucuronate Sulfatase

Arylsulfatase K is the Lysosomal 2-Sulfoglucuronate Sulfatase

  • ACS Chem Biol. 2017 Feb 17;12(2):367-373. doi: 10.1021/acschembio.6b01033.
Omkar P Dhamale 1,  Roger Lawrence 2,  Elena M Wiegmann 3,  Bhahwal A Shah 1,  Kanar Al-Mafraji 1,  William C Lamanna 2,  Torben Lübke 3,  Thomas Dierks 3,  Geert-Jan Boons 1 4,  Jeffrey D Esko 2
Affiliations

Affiliations

  • 1 Complex Carbohydrate Research Center, University of Georgia , Athens, Georgia, United States.
  • 2 Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego , La Jolla, California, United States.
  • 3 Department of Chemistry, Biochemistry I, Bielefeld University , Bielefeld, Germany.
  • 4 Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, and Bijvoet Center for Biomolecular Research, Utrecht University , Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
PMID: 28055182 DOI: 10.1021/acschembio.6b01033
Abstract

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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