Uronyl-2-Sulfotransferase (UST)

  • Jian Liu
  • Tim O’Leary
Reference work entry


Uronyl 2-O-sulfotransferase is a class of enzyme that transfers a sulfo group to the 2-OH position of glucuronic acid (GlcA) or iduronic acid (IdoA) present in chondroitin sulfate polysaccharides. Two closely related 2-O-sulfotransferases have been reported: heparan sulfate 2-O-sulfotransferase (HS2ST) (Kobayashi et al. 1997) and chondroitin uronyl 2-O-sulfotransferase (CS2ST) (Kobayashi et al. 1999). CS2ST specifically sulfates CS substrates that consist of the disaccharide repeating unit of GlcA (or) IdoA linked to a galactosamine residue (Fig. 93.1a), whereas HS2ST sulfates only HS substrates that consist of the disaccharide unit of GlcA (or) IdoA linked to a glucosamine residue (Fig. 93.1b). CS2ST and HS2ST share about 56 % homology in the sulfotransferase domain. The products resulting from HS2ST and CS2ST contain 2-O-sulfated glucuronic acid (GlcA2S) and 2-O-sulfated iduronic acid (IdoA2S) residues. The biological functions of IdoA2S residues present in HS have been implicated in binding to fibroblast growth factors to promote cell growth (Bai 1996; Wang et al. 2010; Xu et al. 2012). However, the biological functions of IdoA2S residues present in CS are less defined. This chapter is primarily focused on the discovery of CS2ST (Kobayashi et al. 1999) and a recent mutagenesis study in CS2ST (Xu et al. 2007).


Glucuronic Acid Dermatan Sulfate Sulfo Group Iduronic Acid Sulfotransferase Activity 
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  1. Bai X, Esko JD (1996) An animal cell mutant defective in heparan sulfate hexuronic acid 2-O-sulfation. J Biol Chem 271:17711–17717PubMedCrossRefGoogle Scholar
  2. Bao X, Pavão MSG et al (2005) A functional dermatan sulfate epitope containing the Iduronate(2-O-sulfate)alpha1-3GalNAc(6-O-sulfate) disaccharide in the mouse brain: Demonstration using a novel monoclonal antibody raised against dermatan sulfate of Ascidian ascidia nigra. J Biol Chem 280:23184–23193PubMedCrossRefGoogle Scholar
  3. Bethea HN, Xu D et al (2008) Redirecting the substrate specificity of heparan sulfate 2-O-sulfotransferase by structurally guided mutagenesis. Proc Natl Acad Sci USA 105:18724–18729PubMedCrossRefGoogle Scholar
  4. Hikino M, Mikami T et al (2003) Oversulfated dermatan sulfate exhibits neurite outgrowth-promoting activity toward embryonic mouse hippocampal neurons. J Biol Chem 278:43744–43754PubMedCrossRefGoogle Scholar
  5. Kobayashi M, Habuchi H et al (1997) Molecular cloning and expression of Chinese hamster ovary cell heparan-sulfate 2-sulfotransferase. J Biol Chem 272:13980–13985PubMedCrossRefGoogle Scholar
  6. Kobayashi M, Sugumaran G et al (1999) Molecular cloning and characterization of a human uronyl 2-sulfotransferase that sulfates iduronyl and glucuronyl residues in dermatan/chondroitin sulfate. J Biol Chem 274:10474–10480PubMedCrossRefGoogle Scholar
  7. Maimone MM, Tollefsen DM (1990) Structure of a dermatan sulfate hexasaccharide that binds to heparin cofactor II with high affinity. J Biol Chem 265:18263–18271PubMedGoogle Scholar
  8. Ohtake S, Kimata K et al (2005) Recognition of sulfation pattern of chondroitin sulfate by Uronosyl 2-O-sulfotransferase. J Biol Chem 280:39115–39123PubMedCrossRefGoogle Scholar
  9. Sen J, Goltz JS et al (2000) Windbeutel is required for function and correct subcellular localization of the Drosophila patterning protein pipe. Development 127:5541–5550PubMedGoogle Scholar
  10. Sen J, Goltz JS et al (1998) Spatially restricted expression of pipe in the Drosophila egg chamber defines embryonic dorsal-ventral polarity. Cell 95:471–481PubMedCrossRefGoogle Scholar
  11. Sergeev P, Streit A et al (2001) The Drosophila dorsoventral determinant PIPE contains ten copies of a variable domain homologous to mammalian heparan sulfate 2-sulfotransferase. Dev Dynam 220:122–132CrossRefGoogle Scholar
  12. Sugiura N, Shioiri T et al (2012) Construction of a chondroitin sulfate library with defined structures and analysis of molecular interactions. J Biol Chem 287(52):43390–400, M112.412676PubMedCrossRefGoogle Scholar
  13. Wang Z, Xu Y et al (2010) Preactivation-based one-pot combinatorial synthesis of heparin-like hexasaccharides for the analysis of heparin-protein interactions. Chem Eur J 16:8365–8375PubMedCentralPubMedCrossRefGoogle Scholar
  14. Xu D, Song D et al (2007) Mutational study of heparan sulfate and chondroitin sulfate 2-O-sulfotransferases J. Biol Chem 282:8356–8367CrossRefGoogle Scholar
  15. Xu Y, Wang Z et al (2012) Redirecting the biological activities of heparan sulfate oligosaccharides using a chemoenzymatic approach. Glycobiology 22:96–106PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Division of Chemical Biology and Medicinal ChemistryEshelman School of Pharmacy, University of North CarolinaChapel HillUSA

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