Biosynthesis of heparin

Lindahl, Ulf; Feingold, David S.; Rodén, Lennart

doi:10.1016/0968-0004(86)90011-3

Cited by 184 publications

(101 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Whereas some authors envisage a limited access of polysaccharide to membrane-bound enzymes (i.e. 3-O-sulfotransferase) in the Golgi apparatus, others suggest that the distribution of recognition sites for the 3-O-sulfotransferase may control the synthesis of the AT-binding site (28,31). Differences in structure and specificity of different 3-O-sulfotransferases, each of them exhibiting unique substrate recognition properties and distinct functional roles, may also influence the distribution of the AT-binding site in both physiological and pathophysiological conditions (9,32).…”

Section: Discussionmentioning

confidence: 99%

Heparin Dodecasaccharide Containing Two Antithrombin-binding Pentasaccharides

Viskov

Elli

Urso

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Heparin is a linear sulfated polysaccharide used clinically as an anticoagulant. Results: A heparin dodecasaccharide, containing two contiguous antithrombin-binding sequences, has been described and characterized for the first time. Conclusion:The dodecasaccharide binds antithrombin in two different molecular assemblies enhancing the probability of the binding and the affinity. Significance: The discovery of this dodecasaccharide improves the knowledge of heparin structure.

show abstract

Section: Discussionmentioning

confidence: 99%

Heparin Dodecasaccharide Containing Two Antithrombin-binding Pentasaccharides

Viskov

Elli

Urso

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Indeed, the available data support this hypothesis (16 -18). As documented by several researchers including ourselves, 3-O-sulfation of glucosamine is a rare modification that constitutes the last step in the biosynthesis of HS (14,15,19,20). We have shown that 3-OST-1 requires an appropriate HS precursor with defined monosaccharide sequence for sulfation to occur and make HS act .…”

mentioning

confidence: 99%

Expression of Heparan Sulfate d-Glucosaminyl 3-O-Sulfotransferase Isoforms Reveals Novel Substrate Specificities

Liu

Shworak

Sînaÿ

et al. 1999

Journal of Biological Chemistry

171

163

View full text Add to dashboard Cite

The 3-O-sulfation of glucosamine residues is an important modification during the biosynthesis of heparan sulfate (HS). Our previous studies have led us to purify and molecularly clone the heparan sulfate D-glucosaminyl 3-O-sulfotransferase (3-OST-1), which is the key enzyme converting nonanticoagulant heparan sulfate (HS inact ) to anticoagulant heparan sulfate (HS act ). In this study, we expressed and characterized the fulllength cDNAs of 3-OST-1 homologous genes, designated as 3-OST-2, 3-OST-3 A , and 3-OST-3 B as described in the accompanying paper ( 35 S]HS suggested that 3-OST-2 transfers sulfate to GlcA2S-GlcNS and IdoA2S-GlcNS; 3-OST-3 A transfers sulfate to IdoA2S-GlcNS. Our results demonstrate that the 3-O-sulfation of glucosamine is generated by different isoforms depending on the saccharide structures around the modified glucosamine residue. This discovery has provided evidence for a new cellular mechanism for generating a defined saccharide sequence in structurally complex HS polysaccharide.

show abstract

“…We suggest that these consensus sequence elements form potential nucleation sites for the recognition of potyanions In proteins and may provide a useful guide In identifying heparln-blnding regions In other proteins. 1112 However, the structural heterogeneity of the acidic mucopolysaccharides with respect to size, carbohydrate composition and charge, 13 and the variety of proteins that are known to bind to these molecules have complicated a detailed molecular analysis of protein-GAG interactions. The most studied system, binding of heparin to a specific domain or site on human antithrombin-lll (AT-III), involves a unique carbohydrate structure representing only a fraction of the total heparin.…”

mentioning

confidence: 99%

Molecular modeling of protein-glycosaminoglycan interactions.

Cardin¹,

Weintraub²

1989

Arteriosclerosis

1,232

993

View full text Add to dashboard Cite

. Predictions were then made as to the heparln-blnding domains In endothellal cell growth factor, purpurln, and antithrombln-lll. Many of the natural sequences conforming to these consensus motifs show prominent amphlpathlc periodicities having both a-hellcal and 0-strand conformations as determined by predictive algorithms and circular dlchroism studies. The heparln-blnding domain of vttronectln was modeled and formed a hydrophlllc pocket that wrapped around and folded over a heparln octasaccharide, yielding a complementary structure. We suggest that these consensus sequence elements form potential nucleation sites for the recognition of potyanions In proteins and may provide a useful guide In identifying heparln-blnding regions In other proteins. 1112 However, the structural heterogeneity of the acidic mucopolysaccharides with respect to size, carbohydrate composition and charge, 13 and the variety of proteins that are known to bind to these molecules have complicated a detailed molecular analysis of protein-GAG interactions. The most studied system, binding of heparin to a specific domain or site on human antithrombin-lll (AT-III), involves a unique carbohydrate structure representing only a fraction of the total heparin. 14 The exact amino acid residues on AT-III or other proteins which comprise their heparin-binding domains have not been fully elucidated.To understand the molecular recognition of heparin by proteins, we recently determined the structure of the heparin-binding regions of apolipoprotein (apo) B-100, the major protein constituent of human plasma low density Received June 10, 1988; revision accepted September 14, 1988. lipoproteins (LDL). The structure of these regions was of particular interest as we hypothesized that they could mediate the interaction of LDL with acidic mucopolysaccharides of arterial tissue. We showed that LDL contains five to seven heparin-binding sites on the lipoprotein surface. 15 The heparin-binding cyanogen bromide peptides of apo B-100 were isolated, and their amino acid sequences were determined. 16 These peptides account for five domains of high positive charge density that we suggest mediate the lipoprotein's interaction with glycosaminoglycans. These same regions were also identified by Weisgraber and Rail. 17 We noticed 16 that these domains in apo B-100 have a sequence similarity to the heparinbinding regions of apo E 1819 and human vitronectin (Vn) 20 with respect to the organization of basic and hydropathic residues. The present study extends our initial observations to other proteins whose functions are modified by heparin. We show that all these proteins contain unique consensus sequences of amino acid residues that are potentially involved in heparin binding. MethodsSecondary structure predictions of Vn peptide conformations were performed by the MSEQ program 21 based on Chou-Fasman algorithms 22 and by the method of Gamier et al. 23 Both methods gave comparable predictions of predominant /3-strand and 0-tum structures, and circular dichroism studies on...

show abstract

Biosynthesis of heparin

Cited by 184 publications

References 19 publications

Heparin Dodecasaccharide Containing Two Antithrombin-binding Pentasaccharides

Heparin Dodecasaccharide Containing Two Antithrombin-binding Pentasaccharides

Expression of Heparan Sulfate d-Glucosaminyl 3-O-Sulfotransferase Isoforms Reveals Novel Substrate Specificities

Molecular modeling of protein-glycosaminoglycan interactions.

Contact Info

Product

Resources

About