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Information on EC 5.1.3.17 - heparosan-N-sulfate-glucuronate 5-epimerase and Organism(s) Danio rerio and UniProt Accession Q29RD8
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5.1.3.17 heparosan-N-sulfate-glucuronate 5-epimeraseIUBMB Comments
The enzyme acts on D-glucosyluronate residues in N-sulfated heparosan polymers, converting them to L-iduronate, thus modifying the polymer to heparan-N-sulfate. The enzyme requires that at least the N-acetylglucosamine residue linked to C-4 of the substrate has been deacetylated and N-sulfated, and activity is highest with fully N-sulfated substrate. It does not act on glucuronate residues that are O-sulfated or are adjacent to N-acetylglucosamine residues that are O-sulfated at the 6 position. Thus the epimerization from D-glucuronate to L-iduronate occurs after N-sulfation of glucosamine residues but before O-sulfation. Not identical with EC 5.1.3.19 chondroitin-glucuronate 5-epimerase or with EC 5.1.3.36, heparosan-glucuronate 5-epimerase.
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Word Map
- 5.1.3.17
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l-iduronic
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d-glucuronic
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epimerization
- proteoglycans
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idoa
- glycosaminoglycans
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glca
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n-sulfated
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2-o-sulfotransferase
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hexuronic
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hspgs
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2-o-sulfation
- mastocytoma
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mannuronan
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lindahl
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o-desulfated
- medicine
- diagnostics
- analysis
- synthesis
The taxonomic range for the selected organisms is: Danio rerio
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
c5-epimerase, hsepi, d-glucuronyl c5-epimerase, glucuronyl c5-epimerase, c5-epi, hg-5epi, hs c5-epimerase, d-glucuronyl c-5 epimerase, heparosan n-sulfate d-glucuronosyl 5-epimerase, hnsg-5epi, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
C5 uronosyl epimerase
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D-Glucuronyl C-5 epimerase
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-
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Epimerase, polyglucuronate
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Glce
Heparosan N-sulfate D-glucuronosyl 5-epimerase
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Heparosan-N-sulfate-D-glucuronosyl-5-epimerase
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
epimerization
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SYSTEMATIC NAME
IUBMB Comments
poly[(1->4)-beta-D-glucuronosyl-(1->4)-N-sulfo-alpha-D-glucosaminyl] glucurono-5-epimerase
The enzyme acts on D-glucosyluronate residues in N-sulfated heparosan polymers, converting them to L-iduronate, thus modifying the polymer to heparan-N-sulfate. The enzyme requires that at least the N-acetylglucosamine residue linked to C-4 of the substrate has been deacetylated and N-sulfated, and activity is highest with fully N-sulfated substrate. It does not act on glucuronate residues that are O-sulfated or are adjacent to N-acetylglucosamine residues that are O-sulfated at the 6 position. Thus the epimerization from D-glucuronate to L-iduronate occurs after N-sulfation of glucosamine residues but before O-sulfation. Not identical with EC 5.1.3.19 chondroitin-glucuronate 5-epimerase or with EC 5.1.3.36, heparosan-glucuronate 5-epimerase.
CAS REGISTRY NUMBER
COMMENTARY
112567-86-9
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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
additional information
?
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key heparan sulfate modifying enzyme, a biosynthetic step that enhances biological activity of heparan sulfate. The enzyme is an important determinant of dorso-ventral axis formation and patterning in zebrafish
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?
additional information
?
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heparin hexasaccharide is product of Glce following O-sulfation, structure of the Glce dimer in complex with heparin hexasaccharide, detailed overview
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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
additional information
?
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key heparan sulfate modifying enzyme, a biosynthetic step that enhances biological activity of heparan sulfate. The enzyme is an important determinant of dorso-ventral axis formation and patterning in zebrafish
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-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
heparin hexasaccharide
mechanism of product inhibition of the enzyme: 2-O- and 6-O-sulfation of heparan sulfate keeps the C5 carbon of L-iduronic acid away from the active-site tyrosine residues, binding structure, detailed overview
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
D-glucuronyl C5-epimerase is a crucial modifying enzyme in the heparan sulfate biosynthesis pathway
physiological function
heparan sulfate (HS) is a glycosaminoglycan present on the cell surface and in the extracellular matrix, which interacts with diverse signal molecules and is essential for many physiological processes including embryonic development, cell growth, inflammation, and blood coagulation. D-Glucuronyl C5-epimerase (Glce) is a crucial enzyme in HS synthesis, converting D-glucuronic acid to L-iduronic acid to increase HS flexibility. This modification of HS is important for protein ligand recognition
additional information
enzyme structure-function relationship, active site structure and function, overview. Three tyrosine residues, Tyr468, Tyr528, and Tyr546, in the active site are crucial for the enzymatic activity
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). Q29RD8_DANRE
585
1
65660
TrEMBL
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
the enzyme forms a dimer with two catalytic sites, each at a positively charged cleft in C-terminal alpha-helical domains binding one negatively charged hexasaccharide
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified enzyme in apo-form and in complex with heparin hexasaccharide, both in a stable dimer conformation, hanging drop vapour diffusion method, mixing of 0.001 ml of 15-20 mg/ml protein in in 20 mM Tris, pH 8.0, 200 mM ammonium acetate, 1 mM dithiothreitol, and 1 mM EDTA, with 0.001 ml of 16% w/v PEG 3350, 0.1 M sodium citrate tribasic dihydrate, pH 5.6, and 2% v/v Tacsimate, pH 5.0 for the unlabeled enzyme and 16% w/v PEG 3350, 0.06 M citric acid, and 0.04 M Bis-Tris propane, pH 4.1, for the SeMet-labeled enzyme, a concentration of 5.0 mg/ml is used for the enzyme complex with heparin oligosaccharide at a molar ratio of 1:5, 20°C, 3 days, X-ray diffraction structure determination and analysis at 1.9-2.2 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H584A
site-directed mutagenesis, the mutant shows 80% reduced activity compared to wild-type
N585A
site-directed mutagenesis, the mutant shows 90% reduced activity compared to wild-type
R154A
site-directed mutagenesis, the mutant shows 60% reduced activity compared to wild-type
R156A
site-directed mutagenesis, the mutant shows over 90% reduced activity compared to wild-type
R396A
site-directed mutagenesis, the mutant shows 90% reduced activity compared to wild-type
R531A
site-directed mutagenesis, the mutant shows about 90% reduced activity compared to wild-type
R543A
site-directed mutagenesis, the mutant shows over 90% reduced activity compared to wild-type
Y149F
site-directed mutagenesis, the mutant shows over 90% reduced activity compared to wild-type
Y177F
site-directed mutagenesis, the mutant shows 40% reduced activity compared to wild-type
Y179F
site-directed mutagenesis, the mutant shows slightly reduced activity compared to wild-type
Y468A
site-directed mutagenesis, the mutant shows over 90% reduced activity compared to wild-type
Y468F
site-directed mutagenesis, the mutant shows 75% reduced activity compared to wild-type
Y482F
site-directed mutagenesis, the mutant shows 20% reduced activity compared to wild-type
Y528A
site-directed mutagenesis, the mutant shows over 90% reduced activity compared to wild-type
Y528F
site-directed mutagenesis, the mutant shows over 90% reduced activity compared to wild-type
Y546A
site-directed mutagenesis, the mutant shows over 90% reduced activity compared to wild-type
Y546F
site-directed mutagenesis, the mutant shows over 90% reduced activity compared to wild-type
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His6-SUMO-tagged enzyme mutants from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, dialysis, tag cleavage, another step of nickel affinity chromatography, and gel filtration of the eluate
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene glce, recombinant expression of enzyme mutant comprising residues Arg50-Asn585 as N-terminally His6-SUMO-tagged enzyme in Escherichia coli strain BL21(DE3), expression of N-terminally His6-SUMO-tagged SeMet-substituted Glce protein in Escherichia coli strain B834, expression of diverse enzyme point mutants
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ghiselli, G.; Farber, S.A.
D-Glucuronyl C5-epimerase acts in dorso-ventral axis formation in zebrafish
BMC Dev. Biol.
5
19
2005
Danio rerio
Cadwallader, A.B.; Yost, H.J.
Combinatorial expression patterns of heparan sulfate sulfotransferases in zebrafish: III. 2-O-sulfotransferase and C5-epimerases
Dev. Dyn.
236
581-586
2007
Danio rerio (Q29RD8), Danio rerio (Q6TS32), Danio rerio
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