Insights into the role of 3-O-sulfotransferase in heparan sulfate biosynthesis

Insights into the role of 3-O-sulfotransferase in heparan sulfate biosynthesis

Author Zorel Meneghetti, Maria Cecilia Autor UNIFESP Google Scholar
Ferreira, Tarsis Gesteira Google Scholar
Tashima, Alexandre Keiji Autor UNIFESP Google Scholar
Chavante, Suely F. Google Scholar
Yates, Edwin Alexander Autor UNIFESP Google Scholar
Liu, Jian Google Scholar
Nader, Helena Bonciani Autor UNIFESP Google Scholar
Lima, Marcelo A. Autor UNIFESP Google Scholar
Abstract 3-O-Sulfotransferase enzyme (sHS) from Litopenaeus vannamei was cloned and its substrate specificity was investigated against a number of GAG structures, including modified heparin polysaccharides and model oligosaccharides. For the heparin polysaccharides, derived from porcine intestinal mucosa heparin, sulfate groups were incorporated into glucosamine residues containing both N-sulfated and N-acetylated substitution within the regions of the predominant repeating disaccharide, either I-A(NS) or I-A(NAc). However, the resulting polysaccharides did not stabilize antithrombin, which is correlated with anticoagulant activity. It was also shown that the enzyme was able to sulfate disaccharides, I-2S-A(NS) and G-A(NAc). The results further illustrate that 3-O-sulfation can be induced outside of the classical heparinbinding pentasaccharide sequence, show that 3-O-sulfation of glucosamine is not a sufficient condition for antithrombin stabilization and suggest that the use of this enzyme during HS biosynthesis may not occur as the final enzymatic step.
Language English
Sponsor CNPq
CAPES
FAPESP
Grant number CNPq: 442357/20141
FAPESP: 2015/0872-3
Date 2017
Published in Organic & Biomolecular Chemistry. Cambridge, v. 15, n. 32, p. 6792-6799, 2017.
ISSN 1477-0520 (Sherpa/Romeo, impact factor)
Publisher Royal Soc Chemistry
Extent 6792-6799
Origin http://dx.doi.org/10.1039/c7ob01533j
Access rights Closed access
Type Article
Web of Science ID WOS:000408361500015
URI http://repositorio.unifesp.br/handle/11600/51374

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