Heparan Sulfate d-Glucosaminyl 3-O-Sulfotransferase-3A SulfatesN-Unsubstituted Glucosamine Residues

Liu, Jian; Shriver, Zach; Blaiklock, Peter; Yoshida, Koichiro; Sasisekharan, Ram; Rosenberg, Robert D.

doi:10.1074/jbc.274.53.38155

Cited by 99 publications

(150 citation statements)

References 45 publications

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“…The enzymes were purified by using heparin-Toyopearl and 3Ј,5Ј-ADP-agarose chromatographies as described previously (11,22). [ 35 S]PAPS was prepared by incubating 0.4 mCi/ml [ 35 S]Na 2 SO 4 (carrier-free, ICN) and 16 mM ATP with 5 mg/ml dialyzed yeast extract (Sigma) (12).…”

Section: Methodsmentioning

confidence: 99%

“…The 3-O-sulfated HS is generated by 3-OST-3, but not by 3-OST-1. It should be noted that 3-OST-3-modified HS is rarely found in HS from natural sources, suggesting that HSV-1 recognizes a unique saccharide structure (11). In addition, a biochemical study revealed that 3-O-sulfated HS provides binding sites for HSV-1 envelope glycoprotein gD, which is a key viral protein involved in entry of HSV-1.…”

Section: -O-sulfotransferase Isoform 3 (3-ost-3) and It Provides Bimentioning

confidence: 99%

“…For instance, HS D-glucosaminyl-3-O-sulfotransferase (3-OST) isoforms generate 3-O-sulfated glucosamine that is linked to different sulfated uronic acid residues. 3-OST-1 transfers sulfate to the 3-OH position of the N-sulfated glucosamine residue that is linked to a glucuronic acid residue at the nonreducing end (GlcUA-GlcNS Ϯ 6S), whereas, 3-OST-3 transfers sulfate to the 3-OH position of the N-unsubstituted glucosamine residue that is linked to a 2-O-sulfated iduronic acid at the nonreducing end (IdoUA2S-GlcNH 2 Ϯ 6S) (11). The differ-ence in substrate specificity of 3-OSTs results in distinct biological functions of the HS modified by 3-OSTs.…”

Section: -O-sulfotransferase Isoform 3 (3-ost-3) and It Provides Bimentioning

confidence: 99%

“…tion D was degraded with nitrous acid at pH 1.5 followed by sodium borohydride reduction. The resultant disaccharides were analyzed by reverse-phase ion pairing HPLC (11). We found that nearly 90% of the [ 35 S]disaccharide was IdoUA2S-[3-35 S]AnMan3S6S (Fig.…”

Section: Structural Characterization Of Fraction D Analysis Of Fractimentioning

confidence: 99%

“…The column was eluted with a linear gradient of KH 2 PO 4 from 350 mM to 1 M for 60 min followed by an additional wash with 1 M KH 2 PO 4 for 20 min at a flow rate of 1 ml/min (11). The fractions containing 35 S-radioactivity were pooled separately and resolved on Bio-Gel P-6.…”

Section: Purification Of the 3-o-sulfatedmentioning

confidence: 99%

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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

116

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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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Section: Methodsmentioning

confidence: 99%

Section: -O-sulfotransferase Isoform 3 (3-ost-3) and It Provides Bimentioning

confidence: 99%

Section: -O-sulfotransferase Isoform 3 (3-ost-3) and It Provides Bimentioning

confidence: 99%

Section: Structural Characterization Of Fraction D Analysis Of Fractimentioning

confidence: 99%

Section: Purification Of the 3-o-sulfatedmentioning

confidence: 99%

See 3 more Smart Citations

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

Self Cite

153

116

View full text Add to dashboard Cite

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Herpes simplex virus: discovering the link between heparan sulphate and hereditary bone tumours

McCormick¹,

Duncan²,

Tufaro³

2000

Rev. Med. Virol.

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Participation of 3‐O‐sulfated heparan sulfates in the protection of macrophages by herpes simplex virus‐1 glycoprotein D and cyclophilin B against apoptosis

et al. 2016

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Heparan sulfates (HS) are involved in numerous biological processes, which rely on their ability to interact with a large panel of proteins. Although the reaction of 3‐O‐sulfation can be catalysed by the largest family of HS sulfotransferases, very few mechanisms have been associated with this modification and to date, only glycoprotein D (gD) of herpes simplex virus‐1 (HSV‐1 gD) and cyclophilin B (CyPB) have been well‐described as ligands for 3‐ O ‐sulfated HS. Here, we hypothesized that both ligands could induce the same responses via a mechanism dependent on 3‐ O ‐sulfated HS. First, we checked that HSV‐1 gD was as efficient as CyPB to induce the activation of the same signalling events in primary macrophages. We then demonstrated that both ligands efficiently reduced staurosporin‐induced apoptosis and modulated the expression of apoptotic genes. In addition to 3‐ O ‐sulfated HS, HSV‐1 gD was reported to interact with other receptors, including herpes virus entry mediator (HVEM), nectin‐1 and ‐2. Thus, we decided to identify the contribution of each binding site in the responses triggered by HSV‐1 gD and CyPB. We found that knock‐down of 3‐ O ‐sulfotransferase 2, which is the main 3‐ O ‐sulfated HS‐generating enzyme in macrophages, strongly reduced the responses induced by both ligands. Moreover, silencing the expression of HVEM rendered macrophages unresponsive to either HSV‐1 gD and CyPB, thus indicating that both proteins induced the same responses by interacting with a complex formed by 3‐ O ‐sulfated HS and HVEM. Collectively, our results suggest that HSV‐1 might hijack the binding sites for CyPB in order to protect macrophages against apoptosis for efficient infection.

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Heparan Sulfate d-Glucosaminyl 3-O-Sulfotransferase-3A SulfatesN-Unsubstituted Glucosamine Residues

Cited by 99 publications

References 45 publications

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

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

Herpes simplex virus: discovering the link between heparan sulphate and hereditary bone tumours

Participation of 3‐O‐sulfated heparan sulfates in the protection of macrophages by herpes simplex virus‐1 glycoprotein D and cyclophilin B against apoptosis

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