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Information on EC 2.8.2.23 - [heparan sulfate]-glucosamine 3-sulfotransferase 1 and Organism(s) Mus musculus

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EC Tree
IUBMB 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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The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
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, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
3'-phosphoadenylyl-sulfate:heparin-glucosamine 3-O-sulfotransferase
-
-
-
-
3-O-sulfotransferase isoform 1
-
3-O-sulfotransferase-1
-
3-O-sulfotransferases-1
-
3-OST-1
3OST1
isoform
glucosaminyl 3-O-sulfotransferase
-
-
-
-
heparan sulfate 3-O-sulfotransferase
-
isoform 1
heparan sulfate 3-O-sulfotransferase 1
-
heparan sulfate 3-O-sulfotransferase isoform-1
-
heparan sulfate 3-O-sulfotransferase-1
-
heparan sulfate D-glucosaminyl 3-O-sulfotransferase
-
-
-
-
heparan sulfate D-glucosaminyl 3-O-sulfotransferase 2
-
-
heparan sulfate glucosamine 3-O-sulfotransferase
-
heparan sulfate sulfotransferase
-
heparin-glucosamine 3-O-sulfotransferase
-
-
-
-
HS3ST-2
-
-
HS3ST1
sulfotransferase, glucosaminyl 3-O-
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
sulfate group transfer
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].
CAS REGISTRY NUMBER
COMMENTARY hide
118113-79-4
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3'-phosphoadenosine 5'-phosphosulfate + heparan sulfate-glucosamine
heparan sulfate 3-O-sulfo glucosamine + adenosine 3',5'-bisphosphate
show the reaction diagram
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
show the reaction diagram
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)
show the reaction diagram
3-phosphoadenylylsulfate + heparan sulfate
adenosine 3',5'-bisphosphate + ?
show the reaction diagram
3-phosphoadenylylsulfate + heparin-glucosamine
?
show the reaction diagram
3-phosphoadenylylsulfate + heparin-glucosamine
adenosine 3',5'-bisphosphate + heparin-glucosamine 3-O-sulfate
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
3'-phosphoadenosine 5'-phosphosulfate + heparan sulfate-glucosamine
heparan sulfate 3-O-sulfo glucosamine + adenosine 3',5'-bisphosphate
show the reaction diagram
3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine
adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate
show the reaction diagram
3-phosphoadenylylsulfate + heparin-glucosamine
?
show the reaction diagram
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
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Na+
the enzyme contains sodium
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
chondriotin sulfate A
15% inhibition at 0.5 mg/ml
low affinity heparin
-
partial inhibition at 0.006 mM, complete inhibition at 0.05 mM
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.01
3'-phosphoadenosine 5'-phosphosulfate
-
wild type
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
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0013
low affinity heparin
-
pH 7.4, 37°C
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
mouse embryonal carcinoma cells
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
-
subcellular localization of HS3ST-2 in neurons, overview
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
HS3S1_MOUSE
311
0
35899
Swiss-Prot
Secretory Pathway (Reliability: 2)
HS3S5_MOUSE
346
1
40471
Swiss-Prot
Secretory Pathway (Reliability: 1)
HS3S6_MOUSE
342
0
37415
Swiss-Prot
other Location (Reliability: 2)
HS3SA_MOUSE
393
0
43483
Swiss-Prot
Secretory Pathway (Reliability: 5)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30000
-
SDS-PAGE
37000
acetylated protein
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
acetylation
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
ternary complex of 3-OST-1/3’-phosphoadenosine 5’-phosphate with an acceptor heptasaccharide substrate, microbatch technique, using 23.6 mM Tris (pH 7.5), 142 mM NaCl, 0.1 M sodium citrate (pH 5.5) and 20% (w/v) PEG 3000
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D95A
-
0.0% of the wild type activity
D95N
-
8.1% of the wild type activity
E76A
-
30.7% of the wild type activity
E76Q
-
15.6% of the wild type activity
E88A
-
63.7% of the wild type activity
E90A
-
0.0% of the wild type activity
E98A
-
65.6% of the wild type activity
H168A
the mutant shows 51.1% activity compared to the wild type enzyme
H168E
the mutant shows 19.1% activity compared to the wild type enzyme
H271A
-
109.0% of the wild type activity
H271F
-
42.0% of the wild type activity
H92A
-
0.0% of the wild type activity
H92F
-
0.0% of the wild type activity
K123A
-
0.2% of the wild type activity
K132A
-
49.1% of the wild type activity
K171A
the mutant shows 83.9% activity compared to the wild type enzyme
K274A
-
17.4% of the wild type activity
K284STP
truncated b3-OST-1 mutant, lacks C-terminal region from residue 284 to 307, exhibits a 200fold reduction in sulfotransferase activity
K68A
-
0.1% of the wild type activity
N167A
the mutant shows 40.4% activity compared to the wild type enzyme
N89A
-
69.5% of the wild type activity
N89D
-
74.4% of the wild type activity
Q163A
-
34.0% of the wild type activity
R197A
-
95.0% of the wild type activity
R268A
the mutant shows 7.2% activity compared to the wild type enzyme
R276A
R67A
-
1.2% of the wild type activity
R67E
-
1.1% of the wild type activity
R72A
-
7.0% of the wild type activity
R72E
-
0.0% of the wild type activity
S273A
-
99.6% of the wild type activity
V164E
the mutant shows 20.3% activity compared to the wild type enzyme
W96A
-
91.6% of the wild type activity
W96F
-
69.1% of the wild type activity
additional information
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
glutathione Sepharose 4B resin column chromatography and Superdex 200 gel filtration
recombinant protein
recombinant protein from Escherichia coli
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in CHO cells
-
expressed in CHO-S, Dual-29, Dual-10, and CHO-gt31 cells
expressed in Escherichia coli BL21 (DE3)-CodonPlusRIL cells
expressed in Sf-9 cells
expression in Escherichia coli strain BL21(DE3)RIL
-
expression in Sf9 cells and Escherichia coli strain BL21-DE3
expression of wild-type and mutant 3-OST-1 in Escherichia coli
HS3ST-2 gene, expression in neurons, expression analysis in vivo, overview
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
-
usefulness of HS3ST-2 as a genetic marker for TrkC-positive mechanosensory neurons
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kusche, M.; Bckstrm, G.; Riesenfeld, J.; Petitou, M.; Choay, J.; Lindahl, U.
Biosynthesis of heparin. O-sulfation of the antithrombin-binding region
J. Biol. Chem.
263
15474-15484
1988
Mus musculus
Manually annotated by BRENDA team
Kusche, M.; Torri, G.; Casu, B.; Lindahl, U.
Biosynthesis of heparin. Availability of glucosaminyl 3-O-sulfation sites
J. Biol. Chem.
265
7292-7300
1990
Mus musculus
Manually annotated by BRENDA team
Razi, N.; Lindahl, U.
Biosynthesis of heparin/heparan sulfate. The D-glucosaminyl 3-O-sulfotransferase reaction: target and inhibitor saccharides
J. Biol. Chem.
270
11267-11275
1995
Mus musculus
Manually annotated by BRENDA team
Zhang, L.; Lawrence, R.; Schwartz, J.J.; Bai, X.; Wei, G.; Esko, J.D.; Rosenberg, R.D.
The effect of precursor structures on the action of glucosaminyl 3-O-sulfotransferase-1 and the biosynthesis of anticoagulant heparan sulfate
J. Biol. Chem.
276
28806-28813
2001
Mus musculus
Manually annotated by BRENDA team
Zhang, L.; Schwartz, J.J.; Miller, J.; Liu, J.; Fritze, L.M.; Shworak, N.W.; Rosenberg, R.D.
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
J. Biol. Chem.
273
27998-28003
1998
Mus musculus
Manually annotated by BRENDA team
Edavettal, S.C.; Carrick, K.; Shah, R.R.; Pedersen, L.C.; Tropsha, A.; Pope, R.M.; Liu, J.
A conformational change in heparan sulfate 3-O-sulfotransferase-1 is induced by binding to heparan sulfate
Biochemistry
43
4680-4688
2004
Mus musculus (O35310)
Manually annotated by BRENDA team
Edavettal, S.C.; Lee, K.A.; Negishi, M.; Linhardt, R.J.; Liu, J.; Pedersen, L.C.
Crystal structure and mutational analysis of heparan sulfate 3-O-sulfotransferase isoform 1
J. Biol. Chem.
279
25789-25797
2004
Mus musculus
Manually annotated by BRENDA team
Munoz, E.; Xu, D.; Kemp, M.; Zhang, F.; Liu, J.; Linhardt, R.J.
Affinity, kinetic, and structural study of the interaction of 3-O-sulfotransferase isoform 1 with heparan sulfate
Biochemistry
45
5122-5128
2006
Mus musculus (O35310)
Manually annotated by BRENDA team
Hasegawa, H.; Wang, F.
Visualizing mechanosensory endings of TrkC-expressing neurons in HS3ST-2-hPLAP mice
J. Comp. Neurol.
511
543-556
2008
Mus musculus
Manually annotated by BRENDA team
Liu, J.; Moon, A.; Sheng, J.; Pedersen, L.
Understanding the substrate specificity of the heparan sulfate sulfotransferases by an integrated biosynthetic and crystallographic approach
Curr. Opin. Struct. Biol.
22
550-557
2012
Mus musculus (O35310)
Manually annotated by BRENDA team
Moon, A.F.; Xu, Y.; Woody, S.M.; Krahn, J.M.; Linhardt, R.J.; Liu, J.; Pedersen, L.C.
Dissecting the substrate recognition of 3-O-sulfotransferase for the biosynthesis of anticoagulant heparin
Proc. Natl. Acad. Sci. USA
109
5265-5270
2012
Mus musculus (O35310)
Manually annotated by BRENDA team
Datta, P.; Li, G.; Yang, B.; Zhao, X.; Baik, J.Y.; Gemmill, T.R.; Sharfstein, S.T.; Linhardt, R.J.
Bioengineered Chinese hamster ovary cells with Golgi-targeted 3-O-sulfotransferase-1 biosynthesize heparan sulfate with an antithrombin-binding site
J. Biol. Chem.
288
37308-37318
2013
Mus musculus (O35310)
Manually annotated by BRENDA team
Thacker, B.E.; Xu, D.; Lawrence, R.; Esko, J.D.
Heparan sulfate 3-O-sulfation: a rare modification in search of a function
Matrix Biol.
35
60-72
2014
Mus musculus (O35310)
Manually annotated by BRENDA team
Sankaranarayanan, N.V.; Bi, Y.; Kuberan, B.; Desai, U.R.
Combinatorial virtual library screening analysis of antithrombin binding oligosaccharide motif generation by heparan sulfate 3-O-Sulfotransferase 1
Comput. Struct. Biotechnol. J.
18
933-941
2020
Mus musculus (O35310)
Manually annotated by BRENDA team