Heparan Sulfate D-Glucosaminyl 3-O-Sulfotransferase-1, -2, -3, and -4

  • Jian Liu
  • Robert D. Rosenberg


Heparan sulfate D-glucosaminyl 3-O-sulfotransferase (HS3ST) is a class of sulfotransferase that transfers the sulfate from 3′-phosphoadenosine 5′-phosphosulfate (PAPS) to the 3-OH of the glucosamine residue. HS3ST was originally exclusively designated the key sulfotransferase to synthesize the antithrombin-binding site in heparan sulfate (HS) to confer its anticoagulant activity (Kusche et al. 1990; Shworak et al. 1996). However, recent studies suggest that HS3ST is present in at least five iso- forms (Shworak et al. 1999). Among these isoforms HS3ST-1, HS3ST-2, HS3ST-3A, and HS3ST-3B have been characterized, and the results allow us to distinguish these enzymes by their DNA/amino acid sequence, biochemical, and biological aspects. Although HS3ST isoforms have similar amino acid sequences at the C-terminus, they differ mainly in the following characteristics: (1) gene locations in the human genome; (2) mRNA expression levels in various human tissues; (3) substrate specificity; and (4) biological functions of enzyme-modified HS (Rosenberg et al. 1997).


Heparan Sulfate Sulfated Glucosamine Pulmonary Artery Smooth Muscle Cell Glucosamine Residue Iduronic Acid 
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  1. Atha DH, Lormeau JC, Petitou M, Rosenberg RD, Choay J (1985) Contribution of monosaccharide residues in heparin binding to antithrombin III. Biochemistry 24:6723–6729PubMedCrossRefGoogle Scholar
  2. Berninsone P, Hirschberg CB (1998) Heparan sulfate/heparin N-deacetylase/N-sulfotransferase: the N-sulfotransferase activity domain is at the carboxyl half of the holoenzyme. J Biol Chem 273:25556–25559PubMedCrossRefGoogle Scholar
  3. Colliec-Jouault S, Shworak NW, Liu J, De Agostini AI, Rosenberg RD (1994) Characterization of a cell mutant specifically defective in the synthesis of anticoagulantly active heparan sulfate. J Biol Chem 271:24953–24958Google Scholar
  4. Danishefsky I, Steiner H, Bella AJ, Friedlander A (1969) Investigation on the chemistry of heparin. J Biol Chem 244:1741–1745PubMedGoogle Scholar
  5. Edge ASB, Spiro RG (1990) Characterization of novel sequences containing 3-O-sulfated glucosamine in glomerular basement membrane heparan sulfate and localization of sulfated disaccharides to a peripheral domain. J Biol Chem 265:15874–15881PubMedGoogle Scholar
  6. Garg HG, Joseph PAM, Yoshida K, Thompson BT, Hales CA (1996) Antiproliferative role of 3-O-sulfate glucosamine in heparin on cultured pulmonary artery smooth muscle cells. Biochem Biophys Res Commun 224:468–473PubMedCrossRefGoogle Scholar
  7. Hernaiz M, Liu J, Rosenberg RD, Linhardt RJ (2000) Enzymatic modification of heparan sulfate on a biochip promotes its interaction with antithrombin III. Biochem Biophys Res Commun 276:292–297PubMedCrossRefGoogle Scholar
  8. Kusche M, Torri G, Casu B, Lindahl U (1990) Biosynthesis of heparin availability of glucosaminyl 3-O-sulfation sites. J Biol Chem 265:7292–7300PubMedGoogle Scholar
  9. Lindahl U, Backstrom G, Thunberg L, Leder IG (1980) Evidence for a 3-O-sulfated D-glucosamine residue in the antithrombin-binding sequence of heparin. Proc Natl Acad Sci USA 77:6551–6555PubMedCrossRefGoogle Scholar
  10. Liu J, Shriver Z, Blaiklock P, Yoshida K, Sasisekharan R, Rosenberg RD (1999b) Heparan sulfate D-glucosaminyl 3-O-sulfotransferase-3A sulfates N-unsubstituted glucosamine residues. J Biol Chem 274:38155–38162PubMedCrossRefGoogle Scholar
  11. Liu J, Shworak NW, Fritze LMS, Edelberg JM, Rosenberg RD (1996) Purification of heparan sulfate D-glucosaminyl 3-O-sulfotransferase. J Biol Chem 271:27072–27082PubMedCrossRefGoogle Scholar
  12. Liu J, Shworak NW, Sinay P, Schwartz JJ, Zhang L, Fritze LMS, Rosenberg RD (1999b) Expression of heparan sulfate D-glucosaminyl 3-O-sulfotransferase isoforms reveals novel substrate specificities. J Biol Chem 274:5185–5192PubMedCrossRefGoogle Scholar
  13. McKeehan WL, Wu X, Kan M (1999) Requirement for anticoagulant heparan sulfate in the fibroblast growth factor receptor complex. J Biol Chem 274:21511–21514PubMedCrossRefGoogle Scholar
  14. Rosenberg RD, Showrak NW, Liu J, Schwartz JJ, Zhang L (1997) Heparan sulfate proteoglycans of the cardiovascular system: specific structures emerge but how is synthesis regulated? J Clin Invest 99:2062–2070PubMedCrossRefGoogle Scholar
  15. Shukla D, Liu J, Blaiklock P, Shworak NW, Bai X, Esko JD, Cohen GH, Eisenberg RJ, Rosenberg RD, Spear PG (1999) A novel role for 3-O-sulfated heparan sulfate in herpes simplex virus 1 entry. Cell 99:13–22PubMedCrossRefGoogle Scholar
  16. Shworak NW, Fritze LMS, Liu J, Butler LD, Rosenberg RD (1996) Cell-free synthesis of anticoagulant heparan sulfate reveals a limiting converting activity that modifies an excess precursor pool. J Biol Chem 271:27063–27071PubMedCrossRefGoogle Scholar
  17. Shworak NW, Liu J, Fritze LMS, Schwartz JJ, Zhang L, Logear D, Rosenberg RD (1997) Molecular cloning and expression of mouse and human cDNAs encoding heparan sulfate D-glucosaminyl 3-O-sulfotransferase. J Biol Chem 272:28008–28019PubMedCrossRefGoogle Scholar
  18. Shworak NW, Liu J, Petros LM, Zhang L, Kobayashi M, Copeland NG, Jenkins NA, Rosenberg RD (1999) Diversity of the extensive heparan sulfate D-glucosaminyl 3-O-sulfotransferase (HS3ST) multigene family. J Biol Chem 274:5170–5184PubMedCrossRefGoogle Scholar
  19. Shworak NW, Shirakawa M, Colliec-Jouault S, Liu J, Mulligan RC, Birinyi LK, Rosenberg RD (1994) Pathway-specific regulation of the biosynthesis of anticoagulantly active heparan sulfate. J Biol Chem 269:24941–24952PubMedGoogle Scholar
  20. Toida T, Yoshida H, Toyoda H, Koshiishi T, Imanari T, Hileman RE, Fromm JR, Linhardt RJ (1997) Structural differences and the presence of unsubstituted amino groups in heparan sulphates from different tissues and species. Biochem J 322:499–506PubMedGoogle Scholar
  21. Zhang L, Schwartz JJ, Miller J, Liu J, Fritze LMS, Shworak NW, Rosenberg RD (1998) The retinoic acid and cAMP-dependent up-regulation of 3-O-sulfotransferase-1 leads to a dramatic augmentation of anticoagulantly active heparan sulfate biosynthesis in F9 embryonal carcinoma cells. J Biol Chem 273:27998–28003PubMedCrossRefGoogle Scholar
  22. Zhang L, Yoshida K, Liu J, Rosenberg RD (1999) Anticoagulant heparan sulfate precursor structures in F9 embryonic carcinoma cells. J Biol Chem 274:5681–5691PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2002

Authors and Affiliations

  • Jian Liu
    • 1
  • Robert D. Rosenberg
    • 2
  1. 1.Division of Medicinal Chemistry and Natural Products, School of PharmacyUniversity of North CarolinaChapel HillUSA
  2. 2.Biology DepartmentMassachusetts Institute of TechnologyCambridgeUSA

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