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Heparan Sulfate/Heparin N-Deacetylase/ N-Sulfotransferase-1

  • Yasuhiro Hashimoto
  • Carlos B. Hirschberg

Abstract

Heparan sulfate N-sulfotransferase-1 (NST-1) was first identified as a Golgi enzyme that catalyzes N-sulfation of the glucosamine moiety (GlcN) of the glycosaminogly- can chain of heparan sulfate (HS). This enzyme was later demonstrated to catalyze another reaction, the N-deacetylation of N-acetylghicosamine (GlcNAc), the step immediately preceding N-sulfation (Wei et al. 1993) (Fig. 1). This enzyme, known now as heparan sulfate N-deacetylase/N-surfotransferase-l (NDST-1), thus catalyzes two sequential reactions that are obligatory initiation steps in the modification of the HS glycosaminoglycan (Lindahl et al. 1998; Bernfield et al. 1999).
Fig. 1

Modification of alternating GlcA and GlcNAc units. The GlcNAc residue is deacetylated to GlcN and subsequently N-acetylated by N-deacetylase/N-sulfotransferase. The disaccharide units are further modified by C5-epimerization and O-sulfation of various positions

Keywords

Heparan Sulfate Pulmonary Hypoplasia Mastocytoma Cell Sulfotransferase Activity Cell Surface Heparan Sulfate Proteoglycan 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Aikawa J, Esko JD (1999a) Molecular cloning and expression of a third member of the heparan sulfate/heparin GlcNAc N-deacetylase/N-sulfotransferase family. J Biol Chem 274:2690–2695PubMedCrossRefGoogle Scholar
  2. Aikawa J, Esko JD (1999b) Molecular cloning and expression of the third and fourth members of the heparan sulfate/heparin N-deacetylase/N-sulfotransferase family. Glycoconj J 16:S40Google Scholar
  3. Bernfield M, Gotte M, Park PW, Reizes O, Fitzgerald ML, Lincecum J, Zako M (1999) Functions of cell surface heparan sulfate proteoglycans. Annu Rev Biochem 68:729–777PubMedCrossRefGoogle Scholar
  4. Berninsone P, Hirschberg CB (1998) Heparan sulfate/heparin N-deacetylase/N-sulfotransferase. J Biol Chem 273:25556–25559PubMedCrossRefGoogle Scholar
  5. Brandan E, Hirschberg CB (1988) Purification of rat liver N-heparan-sulfate sulfotransferase. J Biol Chem 263:2417–2422PubMedGoogle Scholar
  6. Eriksson I, Sandback D, Ek B, Lindahl U, Kjellen L (1994) cDNA cloning and sequencing of mouse mastocytoma glucosaminyl N-deacetylase/N-sulfotransferase, and enzyme involved in the biosynthesis of heparin. J Biol Chem 269:10438–10443PubMedGoogle Scholar
  7. Fan G, Xiao L, Cheng L, Wang X, Sun B, Hu G (2000) Targeted disruption of NDST-1 gene leads to pulmonary hypoplasia and neonatal respiratory distress in mice. FEBS Lett 467:7–11PubMedCrossRefGoogle Scholar
  8. Forsberg E, Pejler G, Ringvall M, Lunderius C, Tomasini-Johansson B, Kusche-Gullberg M, Eriksson I, Ledin J, Hellman L, Kjellen L (1999) Abnormal mast cells in mice deficient in a heparin-synthesizing enzyme. Nature 400:773–776PubMedCrossRefGoogle Scholar
  9. Hashimoto Y, Orellana A, Gil G, Hirschberg CB (1992) Molecular cloning and expression of rat liver N-heparan sulfate sulfotransferase. J Biol Chem 267:15744–15750PubMedGoogle Scholar
  10. Humphries DE, Wong GW, Friend DS, Gurish MF, Qiu W-T, Huang C, Sharpe AH, Stevens RL (1999) Heparin is essential for the storage of specific granule proteases in mast cells. Nature 400:769–772PubMedCrossRefGoogle Scholar
  11. Ishihara M, Guo Y, Wei Z, Yang Z, Swiedler SJ (1993) Regulation of biosynthesis of the basic fibroblast growth factor binding domains of heparan sulfate by heparan sulfate-N-deacetylase/N-sulfotransferase expression. J Biol Chem 268:20091–20095PubMedGoogle Scholar
  12. Kusche-Gullberg M, Eriksson I, Pikas DS, Kjellen L (1998) Identification and expression in mouse of two heparan sulfate glucosaminyl N-deacetylase/N-sulfotransferase genes. J Biol Chem 273:11902–11907PubMedCrossRefGoogle Scholar
  13. Lin X, Perrimon N (1999) Dally cooperates with Drosophila frizzled 2 to transduce wingless signaling. Nature 400:281–284PubMedCrossRefGoogle Scholar
  14. Lindahl U, Kusche-Gullberg M, Kjellen L (1998) Regulated diversity of heparan sulfate. J Biol Chem 273:24979–24982PubMedCrossRefGoogle Scholar
  15. Navia JL, Reisenfeld J, Vann WF, Lindahl U, Roden L (1983) Assay of N-acetylheparosan deacetylase with a capsular polysaccharide from Escherichia coli K5 as substrate. Ann Biochem 135:134–140CrossRefGoogle Scholar
  16. Orellana A, Hirschberg CB (1994) Molecular cloning and expression of a glycosaminoglycan N-acetylglucosaminyl N-deacetylase/N-sulfotransferase from a heparin-producing cell line. J Biol Chem 269:2270–2276PubMedGoogle Scholar
  17. Perrimon N, Bernfield M (2000) Specificities of heparan sulfate proteoglycans in developmental processes. Nature 404:725–728PubMedCrossRefGoogle Scholar
  18. Pettersson I, Kusche M, Unger E, Wlad H, Nylund L, Lindahl U, Kjellen L (1991) Biosynthesis of heparin. J Biol Chem 266:8044–8049PubMedGoogle Scholar
  19. Tsuda M, Kamimura K, Nakato H, Archer M, Staatz W, Fox B, Humphrey M, Olson S, Futch T, Kaluza V, Siegfried E, Stam L, Selleck SB (1999) The cell-surface proteoglycan Dally regulates Wingless signaling in Drosophila. Nature 400:276–280PubMedCrossRefGoogle Scholar
  20. Wei Z, Swiedler SJ (1999) Functional analysis of conserved cysteines in heparan sulfate N-deacetylase-N-sulfotransferases. J Biol Chem 274:1966–1970PubMedCrossRefGoogle Scholar
  21. Wei Z, Swiedler SJ, Ishihara M, Orellana A, Hirschberg CB (1993) A single protein catalyzes both N-deacetylation and N-sulfation during the biosynthesis of heparan sulfate. Proc Natl Acad Sci USA 90:3885–3888PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2002

Authors and Affiliations

  • Yasuhiro Hashimoto
    • 1
  • Carlos B. Hirschberg
    • 2
  1. 1.RIKEN Frontier Research System, Supra-biomolecular System GroupGlyco-chain Functions LaboratorySaitamaJapan
  2. 2.Department of Molecular and Cell BiologyBoston University Goldman School of Dental Medicine, Center for Advanced Biomedical ResearchBostonUSA

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