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

Liu, Jian; Shworak, Nicholas W.; Sînaÿ, Pierre; Schwartz, John J.; Zhang, Lijuan; Fritze, Linda M.S.; Rosenberg, Robert D.

doi:10.1074/jbc.274.8.5185

Cited by 172 publications

(171 citation statements)

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“…Moreover, the control and regulation of the action of these enzymes within the Golgi, result in the biosynthesis of specific binding sites (i.e., the antithrombin III binding site) [17] and domains (i.e., S-domains) [18], remains unclear. Although recent advances in the cloning and recombinant expression of these various enzymes have begun to illuminate specific sequence requirements for these isoforms [19], the real products of HS biosynthesis found in vivo remain poorly understood. In a recent study, the structure of heparan sulfate in control and genetically modified mice was examined [13].…”

Section: Introductionmentioning

confidence: 99%

Isolation and characterization of heparan sulfate from various murine tissues

et al. 2006

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Heparan sulfate (HS), is a proteoglycan (PG) found both in the extracellular matrix and on cell surface. It may represent one of the most biologically important glycoconjugates, playing an essential role in a variety of different events at molecular level. The publication of the mouse genome, and the intensive investigations aimed at understanding the proteome it encodes, has motivated us to initiate studies in mouse glycomics focused on HS. The current study is aimed at determining the quantitative and qualitative organ distribution of HS in mice. HS from brain, eyes, heart, lung, liver, kidney, spleen, intestine and skin was purified from 6-8 week old male and female mice. The recovered yield of HS from these organs is compared with the recovered whole body yield of HS. Structural characterization of the resulting HS relied on disaccharide analysis and 1 H-NMR spectroscopy. Different organs revealed a characteristic HS structure. These data begin to provide a structural understanding of the role of HS in cell-cell interactions, cell signaling

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Section: Introductionmentioning

confidence: 99%

Isolation and characterization of heparan sulfate from various murine tissues

et al. 2006

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“…To address the identity of residue 4, a tetrasaccharide, representing residues 1-4, was prepared by deacetylation followed by nitrous acid degradation at pH 4.5. 8 The resultant tetrasaccharide, which carried a 2-O-sulfated uronic 6 We also attempted to prove the presence of an N-unsubstituted glucosamine residue at the reducing end by treating the octasaccharide with nitrous acid at pH 4.5 followed by sodium borohydride reduction. The molecular mass of the resultant octasaccharide was determined using nESI.…”

Section: Structural Characterization Of the Gd-binding Sitementioning

confidence: 99%

“…The conditions for the nitrous acid degradations under pH 1.5 and 4.5 were described in a prior publication (8). The degraded octasaccharide was analyzed by DEAE-NPR-HPLC.…”

Section: Determination Of the Structure Of A Gd-binding Octasaccharidementioning

confidence: 99%

“…The latter pentasaccharide was generated from GlcNS6S-GlcUA-[3-35 S]GlcNS3S6S-IdoUA2S-GlcNS6SOMe (29) by sequential digestions by glucosamine-6-sulfatase and sulfamidase. 8 The tetrasaccharide was prepared by incubating purified fraction D with hydrazine for deacetylation. The deacetylated octasaccharide was degraded by nitrous acid at pH 4.5 and sodium borohydride reduction.…”

Section: Structural Characterization Of the Gd-binding Sitementioning

confidence: 99%

“…A recent report suggests that the expression levels of various isoforms of each class of HS biosynthetic enzyme contribute to the synthesis of specific saccharide sequences in specific tissues (8). HS N-deacetylase/ N-sulfotransferase, 3-O-sulfotransferase, and 6-O-sulfotransferase are present in multiple isoforms, and each isoform is believed to recognize the saccharide sequence around the modification site to generate a specific sulfated saccharide sequence (8 -10).…”

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Characterization of a Heparan Sulfate Octasaccharide That Binds to Herpes Simplex Virus Type 1 Glycoprotein D

Liu

Shriver

Pope

et al. 2002

Journal of Biological Chemistry

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153

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Herpes simplex virus type 1 utilizes cell surface heparan sulfate as receptors to infect target cells. The unique heparan sulfate saccharide sequence offers the binding site for viral envelope proteins and plays critical roles in assisting viral infections. A specific 3-O-sulfated heparan sulfate is known to facilitate the entry of herpes simplex virus 1 into cells. The 3-O-sulfated heparan sulfate is generated by the heparan sulfate D-glucosaminyl-3-O-sulfotransferase isoform 3 (3-OST-3), and it provides binding sites for viral glycoprotein D (gD). Here, we report the purification and structural characterization of an oligosaccharide that binds to gD. The isolated gDbinding site is an octasaccharide, and has a binding affinity to gD around 18 M, as determined by affinity coelectrophoresis. The octasaccharide was prepared and purified from a heparan sulfate oligosaccharide library that was modified by purified 3-OST-3 enzyme. The molecular mass of the isolated octasaccharide was determined using both nanoelectrospray ionization mass spectrometry and matrix-assisted laser desorption/ionization mass spectrometry. The results from the sequence analysis suggest that the structure of the octasaccharide is a heptasulfated octasaccharide. The proposed structure of the octasaccharide is ⌬UA-GlcNSIdoUA2S-GlcNAc-UA2S-GlcNS-IdoUA2S-GlcNH 2 3S6S. Given that the binding of 3-O-sulfated heparan sulfate to gD can mediate viral entry, our results provide structural information about heparan sulfate-assisted viral entry.Heparan sulfates (HS), 1 highly sulfated polysaccharides, are present on the surface of mammalian cells and in the extracellular matrix in large quantities. HS play critical roles in a variety of biological interactions, including assisting viral infection, regulating blood coagulation and embryonic development, suppressing tumor growth, and controlling the eating behavior of mice by interacting with specific regulatory proteins (1-5). HS is initially synthesized as a copolymer of glucuronic acid and N-acetylated glucosamine by D-glucuronyl and N-acetyl-D-glucosaminyl transferase, followed by various modifications (6). These modifications include C 5 -epimerization of glucuronic acid to form iduronic acid residues, 2-O-sulfation of iduronic and glucuronic acid, N-deacetylation and N-sulfation of glucosamine, as well as 6-O-sulfation and 3-O-sulfation of glucosamine. Numerous HS biosynthetic enzymes have been cloned and characterized (for review, see Esko and Lindahl (7)).The specific sulfated saccharide sequences play critical roles in determining the functions of HS. A recent report suggests that the expression levels of various isoforms of each class of HS biosynthetic enzyme contribute to the synthesis of specific saccharide sequences in specific tissues (8). HS N-deacetylase/ N-sulfotransferase, 3-O-sulfotransferase, and 6-O-sulfotransferase are present in multiple isoforms, and each isoform is believed to recognize the saccharide sequence around the modification site to generate a specific sulfated saccharid...

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