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Information on EC 2.8.2.23 - [heparan sulfate]-glucosamine 3-sulfotransferase 1
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2.8.2.23 [heparan sulfate]-glucosamine 3-sulfotransferase 1IUBMB Comments
This enzyme differs from the other [heparan sulfate]-glucosamine 3-sulfotransferases [EC 2.8.2.29 ([heparan sulfate]-glucosamine 3-sulfotransferase 2) and EC 2.8.2.30 ([heparan sulfate]-glucosamine 3-sulfotransferase 3)] by being the most selective for a precursor of the antithrombin-binding site. It has a minimal acceptor sequence of: -> GlcNAc6S-> GlcA-> GlcN2S*+/-6S-> IdoA2S-> GlcN2S-> , the asterisk marking the target (symbols as in {iupac/2carb/38::2-Carb-38}) using +/- to mean the presence or absence of a substituent, and > to separate a predominant structure from a minor one. Thus Glc(N2S > NAc) means a residue of glucosamine where the N carries a sulfo group mainly but occasionally an acetyl group. [1-4]. It can also modify other precursor sequences within heparan sulfate but this action does not create functional antithrombin-binding sites. These precursors are variants of the consensus sequence: -> Glc(N2S > NAc)+/-6S-> GlcA-> GlcN2S*+/-6S-> GlcA > IdoA+/-2S-> Glc(N2S/NAc)+/-6S-> . If the heparan sulfate substrate lacks 2-O-sulfation of GlcA residues, then enzyme specificity is expanded to modify selected glucosamine residues preceded by IdoA as well as GlcA .
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Word Map
- 2.8.2.23
-
3-o-sulfation
- antithrombin
-
3-osts
-
hsact
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n-sulfated
- 3'-phosphoadenosine
-
antithrombin-binding
- medicine
- pharmacology
- analysis
- synthesis
The enzyme appears in viruses and cellular organisms
Synonyms
3-o-sulfotransferase, 3-ost-1, hs3st1, 3-ost-4, 3-o-sulfotransferase-1, heparan sulfate d-glucosaminyl 3-o-sulfotransferase, hs3st5, heparan sulfate 3-o-sulfotransferase-1, 3-o-sulfotransferase isoform 1, 3-ost1, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
3'-phosphoadenylyl-sulfate:heparin-glucosamine 3-O-sulfotransferase
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3-OST-1
glucosaminyl 3-O-sulfotransferase
heparan sulfate 3-O-sulfotransferase
heparan sulfate 3-O-sulfotransferase 1
heparan sulfate D-glucosaminyl 3-O-sulfotransferase
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heparin-glucosamine 3-O-sulfotransferase
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HS3ST1
sulfotransferase, glucosaminyl 3-O-
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additional information
3-OST-1
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glucosaminyl 3-O-sulfotransferase
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HS3ST1
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additional information
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the enzyme belongs to the 3-OST gene family with two distinct 3-OST family subgroups
additional information
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the enzyme belongs to the family of 3-O-sulfotransferases
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine = adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
This enzyme differs from the other [heparan sulfate]-glucosamine 3-sulfotransferases, EC 2.8.2.29: [heparan sulfate]-glucosamine 3-sulfotransferase 2 and EC 2.8.2.30: [heparan sulfate]-glucosamine 3-sulfotransferase 3 by being the most selective for a precursor of the antithrombin-binding site
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
sulfate group transfer
sulfate group transfer
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PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
3'-phosphoadenylyl-sulfate:[heparan sulfate]-glucosamine 3-sulfotransferase
This enzyme differs from the other [heparan sulfate]-glucosamine 3-sulfotransferases [EC 2.8.2.29 ([heparan sulfate]-glucosamine 3-sulfotransferase 2) and EC 2.8.2.30 ([heparan sulfate]-glucosamine 3-sulfotransferase 3)] by being the most selective for a precursor of the antithrombin-binding site. It has a minimal acceptor sequence of: -> GlcNAc6S-> GlcA-> GlcN2S*+/-6S-> IdoA2S-> GlcN2S-> , the asterisk marking the target (symbols as in {iupac/2carb/38::2-Carb-38}) using +/- to mean the presence or absence of a substituent, and > to separate a predominant structure from a minor one. Thus Glc(N2S > NAc) means a residue of glucosamine where the N carries a sulfo group mainly but occasionally an acetyl group. [1-4]. It can also modify other precursor sequences within heparan sulfate but this action does not create functional antithrombin-binding sites. These precursors are variants of the consensus sequence: -> Glc(N2S > NAc)+/-6S-> GlcA-> GlcN2S*+/-6S-> GlcA > IdoA+/-2S-> Glc(N2S/NAc)+/-6S-> [5]. If the heparan sulfate substrate lacks 2-O-sulfation of GlcA residues, then enzyme specificity is expanded to modify selected glucosamine residues preceded by IdoA as well as GlcA [6].
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CAS REGISTRY NUMBER
COMMENTARY
118113-79-4
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3'-phosphoadenosine 5'-phosphosulfate + heparan sulfate-glucosamine
heparan sulfate 3-O-sulfo glucosamine + adenosine 3',5'-bisphosphate
3'-phosphoadenylyl sulfate + GlcA-beta-(1->4)-GlcNS6S-beta-(1->4)-GlcA-beta-(1->4)-GlcNS6S-alpha-(CH2)5NH2
adenosine 3',5'-bisphosphate + GlcA-beta-(1->4)-GlcNS3S6S-beta-(1->4)-GlcA-beta-(1->4)-GlcNS6S-alpha-(CH2)5NH2
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?
3'-phosphoadenylyl sulfate + GlcA-beta-(1->4)-GlcNS6S-beta-(1->4)-IdoA-beta-(1->4)-GlcNS6S-alpha-(CH2)5NH2
adenosine 3',5'-bisphosphate + GlcA-beta-(1->4)-GlcNS3S6S-beta-(1->4)-IdoA-beta-(1->4)-GlcNS6S-alpha-(CH2)5NH2
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?
3'-phosphoadenylyl sulfate + GlcA-beta-(1->4)-GlcNS6S-beta-(1->4)-IdoA-beta-(1->4)-GlcNS6S-beta-(1->4)-GlcA-beta-(1->4)-GlcNS6S-alpha-(CH2)5NH2
adenosine 3',5'-bisphosphate + GlcA-beta-(1->4)-GlcNS3S6S-beta-(1->4)-IdoA-beta-(1->4)-GlcNS3S6S-beta-(1->4)-GlcA-beta-(1->4)-GlcNS6S-alpha-(CH2)5NH2
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?
3'-phosphoadenylyl sulfate + GlcA-beta-(1->4)-GlcNS6S-beta-(1->4)-IdoA2S-beta-(1->4)-GlcNS6S-alpha-(CH2)5NH2
adenosine 3',5'-bisphosphate + GlcA-beta-(1->4)-GlcNS3S6S-beta-(1->4)-IdoA2S-beta-(1->4)-GlcNS6S-alpha-(CH2)5NH2
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?
3'-phosphoadenylyl sulfate + IdoA-beta-(1->4)-GlcNS6S-beta-(1->4)-IdoA-beta-(1->4)-GlcNS6S-alpha-(CH2)5NH2
adenosine 3',5'-bisphosphate + IdoA-beta-(1->4)-GlcNS3S6S-beta-(1->4)-IdoA-beta-(1->4)-GlcNS6S-alpha-(CH2)5NH2
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?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
3-phosphoadenylylsulfate + GlcNSO3(6-OSO3)-GlcA-GlcNSO3(6-OSO3)-IdoA(2-OSO3)-GlcNSO3(6-OSO3)
adenosine 3',5'-bisphosphate + GlcNSO3(6-OSO3)-GlcA-GlcNSO3(3,6-bisOSO3)-IdoA(2-OSO3)-GlcNSO3(6-OSO3)
3-phosphoadenylylsulfate + heparin-glucosamine
adenosine 3',5'-bisphosphate + heparin-glucosamine 3-O-sulfate
3'-phosphoadenosine 5'-phosphosulfate + heparan sulfate-glucosamine
heparan sulfate 3-O-sulfo glucosamine + adenosine 3',5'-bisphosphate
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?
3'-phosphoadenosine 5'-phosphosulfate + heparan sulfate-glucosamine
heparan sulfate 3-O-sulfo glucosamine + adenosine 3',5'-bisphosphate
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?
3'-phosphoadenosine 5'-phosphosulfate + heparan sulfate-glucosamine
heparan sulfate 3-O-sulfo glucosamine + adenosine 3',5'-bisphosphate
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regulation of blood coagulation
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?
3'-phosphoadenosine 5'-phosphosulfate + heparan sulfate-glucosamine
heparan sulfate 3-O-sulfo glucosamine + adenosine 3',5'-bisphosphate
regulation of blood coagulation
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?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
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?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
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i.e. HSgD+, 3-O-sulfated motifs that bind the gD envelope protein of Herpes simplex virus 1 mediating the viral cellular entry, overview, i.e. HSgD+, 3-O-sulfated motifs that bind the gD envelope protein of Herpes simplex virus 1
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?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
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?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
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?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
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?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
3-OST catalyzes a key substitution in heparan sulfate sequences of biological importance, in particular heparan sulfate anticoagulant activity
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?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
residues R72, R67, K68, K123, and R276 are basic arginine/lysine residues located in a large open cleft of 3-OST-1 that is responsible for heparan sulfate binding
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?
3-phosphoadenylylsulfate + GlcNSO3(6-OSO3)-GlcA-GlcNSO3(6-OSO3)-IdoA(2-OSO3)-GlcNSO3(6-OSO3)
adenosine 3',5'-bisphosphate + GlcNSO3(6-OSO3)-GlcA-GlcNSO3(3,6-bisOSO3)-IdoA(2-OSO3)-GlcNSO3(6-OSO3)
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?
3-phosphoadenylylsulfate + GlcNSO3(6-OSO3)-GlcA-GlcNSO3(6-OSO3)-IdoA(2-OSO3)-GlcNSO3(6-OSO3)
adenosine 3',5'-bisphosphate + GlcNSO3(6-OSO3)-GlcA-GlcNSO3(3,6-bisOSO3)-IdoA(2-OSO3)-GlcNSO3(6-OSO3)
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synthetic polysaccharide, O-sulfation almost exclusively in the 6-O-position of glucosamiyl residues
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?
3-phosphoadenylylsulfate + heparan sulfate
adenosine 3',5'-bisphosphate + ?
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?
3-phosphoadenylylsulfate + heparan sulfate
adenosine 3',5'-bisphosphate + ?
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converts inactive heparan sulfate in the precursor pool into active heparan sulfate
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?
3-phosphoadenylylsulfate + heparan sulfate
adenosine 3',5'-bisphosphate + ?
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enzyme generates sequences containing 6-sulfo-GlcUA-GlcN and 6-sulfo-GlcUA-GlcN
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?
3-phosphoadenylylsulfate + heparin-glucosamine
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enzyme brings about the final stage in biosynthesis of heparin
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3-phosphoadenylylsulfate + heparin-glucosamine
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biosynthesis of heparin/heparan sulfate
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?
3-phosphoadenylylsulfate + heparin-glucosamine
adenosine 3',5'-bisphosphate + heparin-glucosamine 3-O-sulfate
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heparin-related saccharides
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?
3-phosphoadenylylsulfate + heparin-glucosamine
adenosine 3',5'-bisphosphate + heparin-glucosamine 3-O-sulfate
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3-O-sulfation occurs only after the introduction of all other structural components required for the high affinity interaction with antithrombin, including the 6-O-sulfate groups on glucosamine unit 6
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?
3-phosphoadenylylsulfate + heparin-glucosamine
adenosine 3',5'-bisphosphate + heparin-glucosamine 3-O-sulfate
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only heparin with high affinity for antithrombin, i.e. HA heparin, acts as substrate
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?
additional information
?
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heparan sulfate chains contain sulfated domains termed the HS fine structure, which gives HS specific binding affinities for extracellular ligands, heparan sulfate 3-O-sulfotransferases catalyze the transfer of sulfate groups to the 3-O position of glucosamine residues of heparan sulfate, a rare, but essential heparan sulfate chain modification required for HS fine structure
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?
additional information
?
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gD-type-3-OST is essential for a conserved neurogenic signaling pathway regulated by Notch
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?
additional information
?
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use of a chemoenzymatic synthetic approach to synthesize six 3-O-sulfated oligosaccharides, including three hexasaccharides and three octasaccharides. The synthesis is achieved by rearranging the enzymatic modification sequence to accommodate the substrate specificity of 3-O-sulfotransferase 3, analysis of the impact of 3-O-sulfation on the conformation of the pyranose ring of 2-O-sulfated iduronic acid using NMR spectroscopy, and on the correlation between ring conformation and anticoagulant activity. An octasaccharide interacts with antithrombin and displays antifactor Xa activity. The two 3-O-sulfotransferase (3-OST) isoforms, 3-OST-1 and 3-OST-3 (EC 2.8.2.30), are employed to install the GlcNS3S±6S residue into different saccharide sequences. The 3-OST-1 enzyme introduces a sulfation to form a GlcNS3S6S residue that is linked to a GlcA residue at the nonreducing end, forming the disaccharide unit of -GlcAGlcNS3S6S-, whereas the 3-OST-3 enzyme introduces a sulfation to form a GlcNS3S residue that is linked to an IdoA2S residue at the nonreducing end, forming the disaccharide unit of -IdoA2S-GlcNS3S-. Structural and conformational analysis of oligosaccharides, overview
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additional information
?
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use of a chemoenzymatic synthetic approach to synthesize six 3-O-sulfated oligosaccharides, including three hexasaccharides and three octasaccharides. The synthesis is achieved by rearranging the enzymatic modification sequence to accommodate the substrate specificity of 3-O-sulfotransferase 3, analysis of the impact of 3-O-sulfation on the conformation of the pyranose ring of 2-O-sulfated iduronic acid using NMR spectroscopy, and on the correlation between ring conformation and anticoagulant activity. An octasaccharide interacts with antithrombin and displays antifactor Xa activity. The two 3-O-sulfotransferase (3-OST) isoforms, 3-OST-1 and 3-OST-3 (EC 2.8.2.30), are employed to install the GlcNS3S±6S residue into different saccharide sequences. The 3-OST-1 enzyme introduces a sulfation to form a GlcNS3S6S residue that is linked to a GlcA residue at the nonreducing end, forming the disaccharide unit of -GlcAGlcNS3S6S-, whereas the 3-OST-3 enzyme introduces a sulfation to form a GlcNS3S residue that is linked to an IdoA2S residue at the nonreducing end, forming the disaccharide unit of -IdoA2S-GlcNS3S-. Structural and conformational analysis of oligosaccharides, overview
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additional information
?
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HS3ST-2 is a marker for specific subsets of TrkC-expressing cutaneous low-threshold mechanosensory and proprioceptive mechanosensory neurons, overview. HS3ST-2 is involved in formation of sensory endings of nerves in skeletal muscle
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?
additional information
?
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isoform 3OST-1 preferentially sulfates a GlcNS(+/-)6S with a D-glucuronic acid residue on its nonreducing end
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?
additional information
?
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combinatorial virtual library screening analysis of antithrombin binding oligosaccharide motif generation by heparan sulfate 3-O-sulfotransferase 1 (3OST-1). The enzyme prefers very well defined pentasaccharide sequences carrying distinct groups in each of the five residues to generate the antithrombin binding motif. Key residues include His271, Arg72, Arg197 and Lys173, which interact with 6-sulfate, 5-COO-, 2-/6-sulfates and 2-sulfate at the -2, -1, +2, and +1 positions of the precursor pentasaccharide, respectively. Additionally, uncharged residues, especially Gln163 and Asn167, are also identified as playing important roles in recognition, mechanism, overview
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additional information
?
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substrate specificity analysis, overview. For the heparin polysaccharides, derived from porcine intestinal mucosa heparin, sulfate groups are incorporated into glucosamine residues containing both N-sulfated and N-acetylated substitution within the regions of the predominant repeating disaccharide, either I-ANS or I-ANAc. But the resulting polysaccharides do not stabilize antithrombin, which is correlated with anticoagulant activity. The enzyme is able to sulfate disaccharides, I2S-ANS and G-ANAc. 3-O-sulfation can be induced outside of the classical heparin-binding pentasaccharide sequence. Product analysis by NMR spectroscopy, and antithrombin stabilization analysis by differential scanning fluorimetry (DSF). Only chemically modified heparins served as substrates for sHs whereas chondroitin 4-sulfate, chondroitin 6-sulfate, dermatan sulfate and hyaluronic acid do not. Also N-desulfated-N-reacetylated heparin is not modified by sHS. Acceptor substrates are HS, heparin (Hep), modified heparin: O,N-desuIfated-N-reacetylated (HepNAc), and O,N-desuIfated-N-resuIfated (HepNSuIfo). Enzyme sHS does not require either 2-O-, 6-O- or N-sulfate in heparin/HS to modify the polymer and, N-acetylation does not block 3-O-sulfation as anticipated by the hierarchical biosynthetic process where 3-O-sulfation would happen as the final modification step. The data shows that 3-O-sulfation can occur in distinct biosynthetic steps either being the last HS sulfotransferase in the biosynthesis process or the first one in a non-hierarchical way, according to the oligosaccharides tested
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3'-phosphoadenosine 5'-phosphosulfate + heparan sulfate-glucosamine
heparan sulfate 3-O-sulfo glucosamine + adenosine 3',5'-bisphosphate
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
3'-phosphoadenosine 5'-phosphosulfate + heparan sulfate-glucosamine
heparan sulfate 3-O-sulfo glucosamine + adenosine 3',5'-bisphosphate
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regulation of blood coagulation
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-
?
3'-phosphoadenosine 5'-phosphosulfate + heparan sulfate-glucosamine
heparan sulfate 3-O-sulfo glucosamine + adenosine 3',5'-bisphosphate
regulation of blood coagulation
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-
?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
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-
-
-
?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
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-
i.e. HSgD+, 3-O-sulfated motifs that bind the gD envelope protein of Herpes simplex virus 1 mediating the viral cellular entry, overview
-
?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
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-
-
?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
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-
-
?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
-
-
-
?
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
3-OST catalyzes a key substitution in heparan sulfate sequences of biological importance, in particular heparan sulfate anticoagulant activity
-
-
?
3-phosphoadenylylsulfate + heparin-glucosamine
?
-
enzyme brings about the final stage in biosynthesis of heparin
-
-
?
3-phosphoadenylylsulfate + heparin-glucosamine
?
-
biosynthesis of heparin/heparan sulfate
-
-
?
additional information
?
-
-
heparan sulfate chains contain sulfated domains termed the HS fine structure, which gives HS specific binding affinities for extracellular ligands, heparan sulfate 3-O-sulfotransferases catalyze the transfer of sulfate groups to the 3-O position of glucosamine residues of heparan sulfate, a rare, but essential heparan sulfate chain modification required for HS fine structure
-
-
?
additional information
?
-
-
gD-type-3-OST is essential for a conserved neurogenic signaling pathway regulated by Notch
-
-
?
additional information
?
-
-
HS3ST-2 is a marker for specific subsets of TrkC-expressing cutaneous low-threshold mechanosensory and proprioceptive mechanosensory neurons, overview. HS3ST-2 is involved in formation of sensory endings of nerves in skeletal muscle
-
-
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mn2+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
low affinity heparin
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partial inhibition at 0.006 mM, complete inhibition at 0.05 mM
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additional information
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3-O-sulfation may be restricted by other, as yet unidentified, inhibitory structural elements that are preferentially expressed in polysaccharide sequences selected for the generation of heparin with low affinity for antithrombin
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additional information
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2-O-sulfation blocks the action of the enzyme at glucosamine residues located to the reducing side of IdoUA units
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additional information
no inhibition by chondroitin sulfate C, dermatan sulfate, and hyaluronic acid
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5-aza-2'-deoxycytidine
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exposure of chondrosarcoma cells to the DNA-methyltransferase inhibitor 5-Aza-dc up-regulates expression of 3-OST1 mRNA
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Adenocarcinoma
Down-regulation of Gal 3-O-sulfotransferase-2 (Gal3ST-2) expression in human colonic non-mucinous adenocarcinoma.
Atherosclerosis
HS3ST1 genotype regulates antithrombin's inflammomodulatory tone and associates with atherosclerosis.
Breast Neoplasms
The heparan sulfate sulfotransferase 3-OST3A (HS3ST3A) is a novel tumor regulator and a prognostic marker in breast cancer.
Carcinoma, Embryonal
The retinoic acid and cAMP-dependent up-regulation of 3-O-sulfotransferase-1 leads to a dramatic augmentation of anticoagulantly active heparan sulfate biosynthesis in F9 embryonal carcinoma cells.
Chondrosarcoma
Epigenetics: methylation-associated repression of heparan sulfate 3-O-sulfotransferase gene expression contributes to the invasive phenotype of H-EMC-SS chondrosarcoma cells.
Dry Eye Syndromes
Glycogene Expression in Conjunctiva of Patients with Dry Eye: Downregulation of Notch Signaling.
Exostoses
[Primary study on glycan structure in pathopoiesis mechanism of recurrent respiratory papillomatosis]
Herpes Simplex
A role for 3-O-sulfotransferase isoform-4 in assisting HSV-1 entry and spread.
Herpes Simplex
A role for heparan sulfate 3-O-sulfotransferase isoform 2 in herpes simplex virus type 1 entry and spread.
Herpes Simplex
A synthetic heparan sulfate oligosaccharide library reveals the novel enzymatic action of D-glucosaminyl 3-O-sulfotransferase-3a.
Herpes Simplex
Biophysical investigation of human heparan sulfate D-glucosaminyl 3-O-sulfotransferase-3A: a mutual effect of enzyme oligomerisation and glycosaminoglycan ligand binding.
Herpes Simplex
Comprehensive analysis of herpes simplex virus 1 (HSV-1) entry mediated by zebrafish 3-O-Sulfotransferase isoforms: implications for the development of a zebrafish model of HSV-1 infection.
Herpes Simplex
Portable sulphotransferase domain determines sequence specificity of heparan sulphate 3-O-sulphotransferases.
Infections
Comprehensive analysis of herpes simplex virus 1 (HSV-1) entry mediated by zebrafish 3-O-Sulfotransferase isoforms: implications for the development of a zebrafish model of HSV-1 infection.
Infections
Heparin sulphate D-glucosaminyl 3-O-sulfotransferase 3B1 plays a role in HBV replication.
Infections
HSV-1 interaction to 3-O-sulfated heparan sulfate in mouse-derived DRG explant and profiles of inflammatory markers during virus infection.
Infections
Zebrafish 3-O-Sulfotransferase-4 Generated Heparan Sulfate Mediates HSV-1 Entry and Spread.
Neoplasms
Characterization of distinct Gal:3-O-sulfotransferase activities in human tumor epithelial cell lines and of calf lymph node GlcNAc : 6-O-sulfotransferase activity.
Neoplasms
Heparan sulfate proteoglycans undergo differential expression alterations in right sided colorectal cancer, depending on their metastatic character.
Neoplasms
Transdifferentiation of tumor infiltrating innate lymphoid cells during progression of colorectal cancer.
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Cortical gene expression correlates of temporal lobe epileptogenicity.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.006
GlcNSO3(6-OSO3)-GlcA-GlcNSO3(6-OSO3)-IdoA(2-OSO3)-GlcNSO3(6-OSO3)
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pH 7.4, 37°C
additional information
additional information
affinity and kinetic analysis of the interaction of wild-type 3-OST-1 and 3-OST-1 mutants E90Q and R276A with heparan sulfate, overview
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
high expression level of HS3ST1 and low expression level of ZNF263
brenda
additional information
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of trigeminal ganglia, gD-type-3-OST-2 is one of the major enzymes, highly located in neuronal cell bodies not in axons, overview
brenda
additional information
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developmental expression analysis of the 3-OST gene family, mRNA expression patterns in several tissues/organs throughout early zebrafish development, including early cleavage stages, somites, brain, internal body organ primordial, and pectoral fin development, overview
brenda
additional information
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neuronal tissue distribution of 3-O-sulfotransferases, overview
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
transmembrane enzyme with a short cytoplasmic tail at the N-terminus
brenda
additional information
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subcellular localization of HS3ST-2 in neurons, overview
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brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
HS3STs represent the largest family of HS-modifying enzymes, and yet the reaction of 3-O-sulfation is the rarest maturation step, when compared to other sulfations. Seven HS3STs have been characterized in human, for which the expression is dependent on cell type and tissue environment
evolution
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significant structural similarity between sHs and the human heparan sulfate 3-O-suIfotransferase isoform 5, phylogenetic analysis. The enzyme from Litopenaeus vannamei belongs to the O-sulfotransferase family
malfunction
enhanced 3-O-sulfation increases binding to antithrombin, which enhances Factor Xa inhibition, and binding of neuropilin-1
malfunction
expression of the genes encoding HS-modifying enzymes is frequently dysregulated in cancer and other diseases. The enzymes show either anti-oncogenic or tumor-promoting effects
malfunction
expression of the genes encoding HS-modifying enzymes is frequently dysregulated in cancer and other diseases. The enzymes show either anti-oncogenic or tumor-promoting effects. Hypermethylation in proximal regions of the HS3ST1 gene in chondrosarcoma. Exposure to a demethylating agent restores its expression, confirming that aberrant methylation has affected its transcription
malfunction
expression of the genes encoding HS-modifying enzymes is frequently dysregulated in cancer and other diseases. The enzymes show either anti-oncogenic or tumor-promoting effects. Re-expression of HS3ST4 in MDA-MB-231 cells leads to an increase in cell viability and invasion, MDA-MB-231 cells carrying HS3ST4 expression display a significant increase in proliferation and survival
metabolism
HS3ST-mediated 3-O-sulfation leads to at least two distinct forms of 3-O-sulfated motifs. HS3ST1 and HS3ST5 participate in the generation of anticoagulant-active HS/heparin sequences for antithrombin-III, while HS3ST2, HS3ST3A, HS3ST3B, HS3ST4, and HS3ST6 are described to provide the HS-binding motifs for the glycoprotein gD of herpes simplex virus-1 (HSV-1). HS3ST regulations in cancer cells, cell proliferation, and tumor progression, overview
metabolism
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role of 3-O-sulfotransferase in heparan sulfate biosynthesis. 3-O-sulfation can occur in distinct biosynthetic steps either being the last HS sulfotransferase in the biosynthesis process or the first one in a non-hierarchical way, according to the oligosaccharides tested
metabolism
the sulfation at the 3-OH position of glucosamine is an important modification in forming structural domains for heparan sulfate to enable its biological functions. Seven 3-O-sulfotransferase isoforms in the human genome are involved in the biosynthesis of 3-O-sulfated heparan sulfate
metabolism
ZNF263, a C2H2 zinc finger protein, is a negative transcriptional regulator of heparin and heparan sulfate biosynthesis, which shows distinctively low expression in mast cells compared with other (non-heparin-producing) immune cells. ZNF263 is a transcriptional repressor, and its inactivation or silencing enhances mRNA expression of HS3ST1 and HS3ST3A1 (EC 2.8.2.30), enzymes involved in the formation of binding sites for antithrombin and neuropilin-1 (NRP1) and glycoprotein D of herpes simplex virus, respectively. Heparan sulfate (HS) biosynthetic genes exhibit the ZNF263 consensus motif
physiological function
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enzyme expression in resistant Chinese hamster ovary cells promotes susceptibility to herpes simplex virus type-1 infection
physiological function
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isoform 3-OST-1 does not mediate herpes simplex virus-1 entry and spread
physiological function
the enzyme is involved in heparan sulfate biosynthesis
physiological function
HS3ST1 encodes a sulfotransferase that catalyzes the addition of a 3-O-sulfate group on a specific glucosamine unit in heparin and heparan sulfate (HS) that generates the antithrombin-binding site, and thus controls its anticoagulant activity. HS3ST1 is a key enzyme involved in imparting anticoagulant activity to heparin
physiological function
isozymes HS3ST2, HS3ST3B, and HS3ST4 may exhibit a broader selectivity. The HS3ST4 gene is identified as a transcriptional target of TRF2, and increasing TRF2 level leads to an upregulation of HS3ST4 gene expression. Exogenous expression of either TRF2 or HS3ST4 in various tumor cell lines similarly results in increased tumor growth in xenografted mice, which suggests that the expression of this enzyme may be part of a pro-oncogenic pathway. The tumor-promoting effects of HS3ST2, HS3ST3B, and HS3ST4 are related to sustained activation of Src, Akt, and NF-kappaB, and upregulation of the anti-apoptotic proteins survivin and XIAP. Importantly, all these signalling molecules have been well described to play a critical role in promoting tumor growth and resistance to apoptosis
physiological function
pharmaceutical heparin's activity arises from a key high affinity and high selectivity antithrombin binding motif, which forms the basis for its use as an anticoagulant. Generation of the antithrombin-binding motif by the key enzyme involved in heparin biosynthesis, 3-O-sulfotransferase-1 (3OST-1). 3OST-1 recognize glycosaminoglycans with very high selectivity, analysis of the recognition of oligosaccharide sequences by 3OST-1 using combinatorial virtual library screening (CVLS) algorithm on hundreds of tetrasaccharide and hexasaccharide sequences, two libraries of tetrasaccharide and one library of hexasaccharide topologies are constructed using naturally occurring saccharide residues including GlcNS, GlcNS6S, GlcNAc, GlcNAc6S, IdoA, IdoA2S and GlcA. For tetrasaccharide sequences, the nonreducing end (NRE) residue is either a GlcN or a UA, identification of high affinity/high specificity sequences binding to 3OST-1 utilizing the CVLS algorithm, detailed overview. The antithrombin-binding motif (ABM) in heparin/heparan sulfate (Hp/HS) is introduced by 3OST-1 when it acts on the precursor sequence to convert the 3-OH group of central GlcN residue to the 3-O-sulfate group
physiological function
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role of 3-O-sulfotransferase in heparan sulfate biosynthesis. 3-O-sulfation can be induced outside of the classical heparin-binding pentasaccharide sequence, and 3-O-sulfation of glucosamine is not a sufficient condition for antithrombin stabilization and suggest that the use of this enzyme during haparan sulfate (HS) biosynthesis may not occur as the final enzymatic step. Thermostabilizing effects of sHS-treated heparins on antithrombin
additional information
enzyme structure modeling using the crystal structure of the 3OST-1-HS heptasaccharide complex (PDB ID 3UAN), overview. Heparan sulfate (HS) and heparin are sulfated glycosamino-glycans (GAG) composed of repeating disaccharide units of (1->4)-linked alpha-D-glucosamine and uronic acid. Whereas HS disaccharides are predominantly formed by beta-D-glucuronate and alpha-D-glucosamine that can be either N-acetylated or N-sulfated, heparin is more sulfated, composed mainly of alpha-L-iduronate 2-O-sulfate and alpha-D-glucosamine N,6-sulfate
additional information
to date, only a few ligands are known to selectively interact with 3-O-sulfated motifs, whereas hundreds of HS-binding proteins have been identified
additional information
to date, only a few ligands are known to selectively interact with 3-O-sulfated motifs, whereas hundreds of HS-binding proteins have been identified
additional information
to date, only a few ligands are known to selectively interact with 3-O-sulfated motifs, whereas hundreds of HS-binding proteins have been identified
additional information
to date, only a few ligands are known to selectively interact with 3-O-sulfated motifs, whereas hundreds of HS-binding proteins have been identified
additional information
-
to date, only a few ligands are known to selectively interact with 3-O-sulfated motifs, whereas hundreds of HS-binding proteins have been identified
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UNIPROT
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