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C5 uronosyl epimerase
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D-Glucuronyl C-5 epimerase
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D-glucuronyl C5-epimerase
Epimerase, polyglucuronate
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glucuronosyl C-5 epimerase
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heparan sulfate C-5 epimerase
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Heparan sulfate C5-epimerase
Heparosan N-sulfate D-glucuronosyl 5-epimerase
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heparosan-glucuronate 5-epimerase
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Heparosan-N-sulfate-D-glucuronosyl-5-epimerase
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HS glucuronyl C5-epimerase
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C5-epi
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C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
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D-glucuronyl C5-epimerase
Vibrio cholerae serotype O1 CO845
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D-glucuronyl C5-epimerase
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Glce
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glucuronyl C5-epimerase
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glucuronyl C5-epimerase
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glucuronyl C5-epimerase
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Heparan sulfate C5-epimerase
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Heparan sulfate C5-epimerase
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HS C5-epimerase
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Hsepi
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GlcA-beta-(1->4)-GlcNAc-beta-(1->4)-GlcA-beta-(1->4)-GlcNS-beta-(1->4)-GlcA-beta-(1->4)-GlcNAc-beta-(1->4)-GlcA-beta-(1->4)-2,5-andydro-D-mannitol
GlcA-beta-(1->4)-GlcNAc-beta-(1->4)-GlcA-beta-(1->4)-GlcNS-beta-(1->4)-IdoA-beta-(1->4)-GlcNAc-beta-(1->4)-GlcA-beta-(1->4)-2,5-andydro-D-mannitol
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i.e. Octa-4
i.e. epi-Octa-4
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ir
GlcA-beta-(1->4)-GlcNAc-beta-(1->4)-GlcA-beta-(1->4)-GlcNS-beta-(1->4)-GlcA-beta-(1->4)-GlcNS-beta-(1->4)-GlcA-beta-(1->4)-2,5-andydro-D-mannitol
GlcA-beta-(1->4)-GlcNAc-beta-(1->4)-GlcA-beta-(1->4)-GlcNS-beta-(1->4)-GlcA-beta-(1->4)-GlcNS-beta-(1->4)-GlcA-beta-(1->4)-2,5-andydro-D-mannitol
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i.e. Octa-3, two GlcA units in Octa-1 are susceptible to C5-epi modification, and both epimerization sites are reversible
i.e. epi-Octa-3
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ir
GlcA-beta-(1->4)-GlcNAc-beta-(1->4)-GlcA-beta-(1->4)-GlcNS-beta-(1->4)-GlcA-beta-(1->4)-GlcNS-beta-(1->4)-GlcA-beta-(1->4)-GlcNS-beta-(1->4)-GlcA-beta-(1->4)-2,5-andydro-D-mannitol
GlcA-beta-(1->4)-GlcNAc-beta-(1->4)-GlcA-beta-(1->4)-GlcNS-beta-(1->4)-IdoA-beta-(1->4)-GlcNS-beta-(1->4)-IdoA-beta-(1->4)-GlcNS-beta-(1->4)-GlcA-beta-(1->4)-2,5-andydro-D-mannitol
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i.e. Deca-8 with GlcA-beta-(1->4)-GlcNAc-beta-(1->4)-GlcA-beta-(1->4)-GlcNS-beta-(1->4)-GlcA(irreversible site)-beta-(1->4)-GlcNS-beta-(1->4)-GlcA (reversible site)-beta-(1->4)-GlcNS-beta-(1->4)-GlcA-beta-(1->4)-2,5-andydro-D-mannitol
i.e. epi-Deca-8
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?
GlcA-beta-(1->4)-GlcNH2-beta-(1->4)-GlcA-beta-(1->4)-GlcNS-beta-(1->4)-GlcA-beta-(1->4)-GlcNS-beta-(1->4)-GlcA-beta-(1->4)-2,5-andydro-D-mannitol
GlcA-beta-(1->4)-GlcNH2-beta-(1->4)-GlcA-beta-(1->4)-GlcNS-beta-(1->4)-IdoA-beta-(1->4)-GlcNS-beta-(1->4)-GlcA-beta-(1->4)-2,5-andydro-D-mannitol
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i.e. Octa-6
i.e. epi-Octa-6
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r
GlcA-beta-(1->4)-GlcNS-beta-(1->4)-GlcA-beta-(1->4)-GlcNS-beta-(1->4)-GlcA-beta-(1->4)-2,5-andydro-D-mannitol
GlcA-beta-(1->4)-GlcNS-beta-(1->4)-IdoA-beta-(1->4)-GlcNS-beta-(1->4)-GlcA-beta-(1->4)-2,5-andydro-D-mannitol
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i.e. Hexa-7
i.e. epi-Hexa-7
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r
GlcA-beta-(1->4)-GlcNS-beta-(1->4)-GlcA-beta-(1->4)-GlcNS-beta-(1->4)-GlcA-beta-(1->4)-GlcNAc-beta-(1->4)-GlcA-beta-(1->4)-2,5-andydro-D-mannitol
GlcA-beta-(1->4)-beta-(1->4)-GlcNS-beta-(1->4)-L-IdoA-alpha-(1->4)-GlcNS-beta-(1->4)-L-IdoA-alpha-(1->4)-GlcNAc-beta-(1->4)-GlcA-beta-(1->4)-2,5-andydro-D-mannitol
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i.e. Octa-1, two GlcA units in Octa-1 are susceptible to C5-epi modification, and both epimerization sites are reversible
i.e. epi-Octa-1
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r
GlcA-beta-(1->4)-GlcNS-beta-(1->4)-GlcA-beta-(1->4)-GlcNS-beta-(1->4)-GlcA-beta-(1->4)-GlcNS-beta-(1->4)-GlcA-beta-(1->4)-2,5-andydro-D-mannitol
GlcA-beta-(1->4)-GlcNS-beta-(1->4)-IdoA-beta-(1->4)-GlcNS-beta-(1->4)-IdoA-beta-(1->4)-GlcNS-beta-(1->4)-GlcA-beta-(1->4)-2,5-andydro-D-mannitol
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i.e. Octa-2
i.e. epi-Octa-2
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r
heparan sulfate-derived polysaccharide
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heparin-derived polysaccharide
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heparosan N-sulfate D-glucuronate
heparosan N-sulfate L-iduronate
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Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
uronic acid residues
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additional information
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Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
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?
Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
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Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
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Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
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Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
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heparosan N-sulfate prepared by metabolic labeling of a capsular polysaccharide from E. coli K5 and subsequent chemical partial N-deacetylation and N-sulfation. Approximately 30% of the D-glucuronyl residues located between two N-sulfated glucosamine units are converted to L-iduronyl units
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?
Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
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Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
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?
Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
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Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
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C5-epimerization is irreversible in vivo
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ir
Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
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development of a coupled assay method using the enzyme and a 2-O-sulfotransferase mutant 2OST Y94I, overview
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Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
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?
Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
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Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
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a D-glucuronosyl residue is recognized as a substrate if it is linked at C-1 to an N-acetyl glucosamine residue and at C-4 to a N-sulfated unit. Large substrates are preferred
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Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
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the enzyme controle heparan sulfate chain flexibility, its activity, modifiying the substrate, is required for proper lymphoid organ development, overview
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Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
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Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
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the enzyme controle heparan sulfate chain flexibility, its activity, modifiying the substrate, is required for proper lymphoid organ development, overview
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additional information
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enzyme catalyzes formation of L-iduronic acid residues in the course of heparin biosynthesis
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additional information
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enzyme is involved in the biosynthesis of heparan sulfate in liver
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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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additional information
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limiting factor in dermatan sulfate biosynthesis
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?
additional information
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the D-glucuronyl C5-epimerase gene is transcriptionally activated through the beta-catenin-TCF4 pathway
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additional information
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the D-glucuronyl C5-epimerase gene is transcriptionally activated through the beta-catenin-TCF4 pathway
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additional information
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the enzyme is known for being a two-way catalytic enzyme, displaying a reversible catalytic mode by converting a glucuronic acid to an iduronic acid residue, and vice versa. The enzyme can also serve as a one-way catalyst to convert a glucuronic acid to an iduronic acid residue, displaying an irreversible catalytic mode. The reversible or irreversible catalytic mode strictly depends on the saccharide substrate structures
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?
additional information
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oligosaccharides containing a nonreducing end GlcNS residue immediately adjacent to the EPS residue are reactive to the enzyme. In contrast, when the GlcNS is replaced with GlcNAc, the oligosaccharide is no longer a substrate of the enzyme, substrate specificity, overview. No activity with GlcA-beta-(1->4)-GlcNAc-beta-(1->4)-GlcA-beta-(1->4)-GlcNAc-beta-(1->4)-GlcA-beta-(1->4)-GlcNAc-beta-(1->4)-GlcA-beta-(1->4)-2,5-andydro-D-mannitol. Determination of epimerization sites in different substrates and reaction reversibility using D2O and tandem mass spectrometry, critical role of N-sulfated glucosamine at the nonreducing end of the epimerization site
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additional information
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development and evaluation of a rapid, nonradioactive assay for measuring heparan sulfate C-5 epimerase activity using hydrogen/deuterium exchange-mass spectrometry, overview. The method involves the following steps: H/D exchange upon epimerization of the substrate with HS C5-epimerase, low-pH nitrous acid treatment of the substrate, the separation of low-pH nitrous acid-cleaved disaccharides using HPLC, and mass spectrometry analysis
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additional information
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development and evaluation of a rapid, nonradioactive assay for measuring heparan sulfate C-5 epimerase activity using hydrogen/deuterium exchange-mass spectrometry, overview. The method involves the following steps: H/D exchange upon epimerization of the substrate with HS C5-epimerase, low-pH nitrous acid treatment of the substrate, the separation of low-pH nitrous acid-cleaved disaccharides using HPLC, and mass spectrometry analysis
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additional information
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recombinant enzyme HG-5epi, expressed in insect cells, epimerizes GlcA residues in heparosan, but not in N-sulfated-heparosan. Conversion of IdoA to GlcA is also catalyzed by HG-5epi when completely desulfated N-acetylated heparin is used as the substrate, indicating a reversible reaction mechanism. At equilibrium of the epimerization, the proportion of IdoA in the reaction product reaches up to 30% of total hexuronic acid. The recombinant enzyme catalyzes the epimerization of non-sulfated heparosan, product identification by using a combination of anion-exchange HPLC and postcolumn fluorescent labeling system
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additional information
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recombinant enzyme HG-5epi, expressed in insect cells, epimerizes GlcA residues in heparosan, but not in N-sulfated-heparosan. Conversion of IdoA to GlcA is also catalyzed by HG-5epi when completely desulfated N-acetylated heparin is used as the substrate, indicating a reversible reaction mechanism. At equilibrium of the epimerization, the proportion of IdoA in the reaction product reaches up to 30% of total hexuronic acid. The recombinant enzyme catalyzes the epimerization of non-sulfated heparosan, product identification by using a combination of anion-exchange HPLC and postcolumn fluorescent labeling system
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additional information
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enzyme catalyzes formation of L-iduronic acid residues in the course of heparin biosynthesis
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additional information
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L-iduronosyl moieties are formed after N-sulfation but before O-sulfation
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?
additional information
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the enzyme is involved in the biosynthesis of heparin and heparan sulfate
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?
additional information
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the enzyme is involved in the biosynthesis of heparin and heparan sulfate
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?
additional information
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analysis of N-sulfation and glycosylation patterns, as well as chain lengths of heparan sulfate samples from wild-type and mutant cells, overview
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heparosan N-sulfate D-glucuronate
heparosan N-sulfate L-iduronate
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?
Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
additional information
?
-
Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
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?
Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
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?
Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
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?
Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
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?
Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
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C5-epimerization is irreversible in vivo
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ir
Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
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?
Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
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the enzyme controle heparan sulfate chain flexibility, its activity, modifiying the substrate, is required for proper lymphoid organ development, overview
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?
Heparosan-N-sulfate D-glucuronate
Heparosan-N-sulfate L-iduronate
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the enzyme controle heparan sulfate chain flexibility, its activity, modifiying the substrate, is required for proper lymphoid organ development, overview
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?
additional information
?
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enzyme catalyzes formation of L-iduronic acid residues in the course of heparin biosynthesis
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-
?
additional information
?
-
-
enzyme is involved in the biosynthesis of heparan sulfate in liver
-
-
?
additional information
?
-
-
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
-
-
?
additional information
?
-
-
limiting factor in dermatan sulfate biosynthesis
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?
additional information
?
-
the D-glucuronyl C5-epimerase gene is transcriptionally activated through the beta-catenin-TCF4 pathway
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?
additional information
?
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the D-glucuronyl C5-epimerase gene is transcriptionally activated through the beta-catenin-TCF4 pathway
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?
additional information
?
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the enzyme is known for being a two-way catalytic enzyme, displaying a reversible catalytic mode by converting a glucuronic acid to an iduronic acid residue, and vice versa. The enzyme can also serve as a one-way catalyst to convert a glucuronic acid to an iduronic acid residue, displaying an irreversible catalytic mode. The reversible or irreversible catalytic mode strictly depends on the saccharide substrate structures
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?
additional information
?
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enzyme catalyzes formation of L-iduronic acid residues in the course of heparin biosynthesis
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?
additional information
?
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L-iduronosyl moieties are formed after N-sulfation but before O-sulfation
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?
additional information
?
-
the enzyme is involved in the biosynthesis of heparin and heparan sulfate
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?
additional information
?
-
-
the enzyme is involved in the biosynthesis of heparin and heparan sulfate
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?
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evolution
D-glucuronyl C5-epimerase activity and presence of L-iduronic acid seem to be intrinsic properties of cells from prokaryotes to humans
malfunction
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complex deregulation of GLCE expression in prostatic diseases compared with healthy prostate tissue
malfunction
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homozygous enzyme mutant flies are viable and fertile with only minor morphological defects, including the formation of an ectopic crossvein in the wing, but they have a short lifespan. Loss of Hsepi results in a significant impairment of 2-O-sulfation and induces compensatory increases in N- and 6-O-sulfation. Simultaneous block of Hsepi glucuronyl C5-epimerase and heparan sulfate 6-O-sulfotransferase activity disrupted tracheoblast formation, a well established FGF-dependent process. The increase in 6-O-sulfation in Hsepi mutants is critical for the rescue of FGF signaling
metabolism
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the enzyme catalyzes a step in the heparan sulfate biosynthesis
metabolism
D-glucuronyl C5-epimerase is a key enzyme involved in the biosynthesis of heparan sulfate proteoglycans, which has an important role in cell-cell and cell-matrix interactions and signaling
metabolism
the enzyme is probably involved in bacterial capsular polysaccharide biosynthesis, it shows catalytic properties similar to murine heparan sulfate D-glucuronyl C5-epimerase. The biosynthesis of these complex polysaccharides involves complicated reactions that turn the simple glycosaminoglycan backbone into highly heterogeneous structures. One of the modification reactions is the epimerization of D-glucuronic acid to its C5-epimer L-iduronic acid, which is essential for the function of heparan sulfate
metabolism
D-glucuronyl C5-epimerase is a crucial modifying enzyme in the heparan sulfate biosynthesis pathway
physiological function
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heparan sulfate modification by the enzyme is essential for controlling activity of molecules that are instructive for early lymphoid tissue morphogenesis, but may be dispensable in later developmental stages or for lymphocyte maturation and differentiation, overview
physiological function
D-glucuronyl C5-epimerase inhibits U2020 tumor xenograft growth in vivo, the enzyme affects lung cancer cell proliferation and tumor growth by inhibiting tumor angiogenesis and invasion/metastasis pathways
physiological function
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during the biosynthesis of heparan sulfate, glucuronyl C5-epimerase catalyzes C5-epimerization of glucuronic acid, converting it to iduronic acid. C5-epimerization is required for normal heparan sulfate sulfation. Role of Hsepi in development, overview. Genetic interactions between the enzyme and HSPG core protein genes during wing margin formation
physiological function
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heparansulfate proteoglycans play an important role in cell-cell and cell-matrix interactions and signaling, and one of the key enzymes in heparansulfate biosynthesis is D-glucuronyl C5-epimerase. The enzyme has a tumor suppressor function in breast and lung carcinogenesis
physiological function
D-glucuronyl C5-epimerase (GLCE) is one of the key heparan sulfate biosynthetic enzymes, responsible for the epimerization of D-glucuronic acid (GlcA) to L-iduronic acid (IdoA) in the heparan sulfate proteoglycans (HSPGs). IdoA presence increases a flexibility of HS chains and facilitates interaction of HSPGs with numerous extracellular and cell surface ligands including growth factors. The dynamic cooperation of proteoglycans, growth factor receptors, and integrins determines cell behavior, polarity, migration, differentiation, proliferation, and survival both in physiological and pathological conditions. D-glucuronyl C5-epimerase (GLCE) is involved in breast and lung carcinogenesis as a potential tumor suppressor gene, acting through inhibition of tumor angiogenesis and invasion/metastasis pathways. In prostate tumors, increased GLCE expression is associated with advanced disease, suggesting versatile effects of GLCE in different cancers, potential cancer-promoting effect of GLCE in prostate cancer and involvement of GLCE in carcinogenesis. GLCE up-regulation plus expression pattern of a panel of six genes, discriminating morphologically different prostate cancer cell sub-types, is suggested as a potential marker of aggressive prostate cancer
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
physiological function
heparin and heparan sulfate (HS) glycosaminoglycans have important roles in anticoagulation, human development, and human diseases. HS C5-epimerase, which catalyzes the reversible epimerization of GlcA to IdoA, is a crucial enzyme involved in the biosynthesis of heparin-related biomolecules
physiological function
iduronic acid (IdoA) is a critical component of heparan sulfate in its interaction with functional proteins. Heparosan-N-sulfate-glucuronate 5-epimerase (HNSG-5epi) converts D-glucuronic acid (GlcA) residues in N-sulfated heparosan (NS-heparosan), as an intermediate in heparan sulfate biosynthesis, to IdoA. HG-5epi (heparosan-glucuronate 5-epimerase) is involved in acharan sulfate biosynthesis possesia distinct substrate specificity in Achatina fulica
physiological function
the enzyme is involved in heparan sulfate biosynthesis
physiological function
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heparan sulfate modification by the enzyme is essential for controlling activity of molecules that are instructive for early lymphoid tissue morphogenesis, but may be dispensable in later developmental stages or for lymphocyte maturation and differentiation, overview
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additional information
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disaccharide analyses of chondroitin sulfate from enzyme wild-type and mutant strains, with or without additional mutation of heparan sulfate 2-O-sulfotransferase, overview
additional information
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the biphasic mode of C5-epi offers a mechanism to regulate the biosynthesis of heparan sulfate with the desired biological functions
additional information
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the enzyme may be used as a potential model to study the functional role of intratumor cell heterogeneity in prostate cancer progression
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
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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
Y146A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
Y162A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
Y168A
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site-directed mutagenesis, inactive mutant
Y210A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
Y222A
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site-directed mutagenesis, inactive mutant
additional information
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construction of enzyme deficient strains ussing P-element transposase exscision mutagenesis, removal of the entire Hsepi coding sequence, generation of viable and fertile homozygous mutants for Hsepid12 and Hsepid13
additional information
high cell density fed-batch cultivation of recombinant Escherichia coli strains expressing 2-O-sulfotransferase and C5-epimerase at high level for the production of bioengineered heparin, method, overview. The first enzymatic step in this process uses heparan sulfate biosynthetic enzymes, 2-O-sulfotransferase (2-OST) and C5-epimerase (C5-epi), expressed as MBP-tagged proteins in Escherichia coli, to convert N-sulfo heparosan into an intermediate polysaccharide rich in -GlcNS(1->4)IdoA2S- sequences (where S is sulfo and IdoA is alpha-L-iduronic acid). This critical step in bioengineered heparin preparation relies on the use of recombinant arylsulfotransferase IV (AST-IV) to regenerate 3'-phospho adenosine-5'-phosphosulfate (PAPS) using p-nitrophenylsulfate as a sacrificial sulfur donor, one-pot reaction
additional information
generation of a soluble form of the enzyme HG-5epi by replacement of the transmembrane domain (N-terminal 33 amino acids) with the immunoglobulin Kappa signal sequence and a FLAG tag
additional information
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generation of a soluble form of the enzyme HG-5epi by replacement of the transmembrane domain (N-terminal 33 amino acids) with the immunoglobulin Kappa signal sequence and a FLAG tag
additional information
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generation of Glce null mutant mice, that show a strongly reduced size of the fetal spleen and a spectrum of defects in thymus and lymph node development ranging from dislocation to complete loss of the organ, overview. Transplantation of wild-type lymph nodes allows undisturbed lymphocyte maturation, phenotype, overview
additional information
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generation of Hsepi null mutant mice showing a lethal phenotype with selective organ defects but remarkably little effect on other organ systems, phenotype, overview. Heparan sulfate produced by enzyme-deficient MEF cells is devoid of L-iduronic acid residues, but shows up-regulated N- and 6-O-sulfation compared with wild-type, Hsepi-/- MEF cells proliferate and migrate similarly to wild-type cells. Restricted proliferation and migration of Hsepi mutant cells in response to FGF2 stimulation
additional information
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generation of Glce null mutant mice, that show a strongly reduced size of the fetal spleen and a spectrum of defects in thymus and lymph node development ranging from dislocation to complete loss of the organ, overview. Transplantation of wild-type lymph nodes allows undisturbed lymphocyte maturation, phenotype, overview
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EJ-ras oncogene transfection of endothelial cells upregulates the expression of syndecan-4 and downregulates heparan sulfate sulfotransferases and epimerase
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Heparan sulfate C5-epimerase is essential for heparin biosynthesis in mast cells
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Grigorieva, E.; Eshchenko, T.; Rykova, V.I.; Chernakov, A.; Zabarovsky, E.; Sidorov, S.V.
Decreased expression of human D-glucuronyl C5-epimerase in breast cancer
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2008
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Jia, J.; Maccarana, M.; Zhang, X.; Bespalov, M.; Lindahl, U.; Li, J.P.
Lack of L-iduronic acid in heparan sulfate affects interaction with growth factors and cell signaling
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Li, K.; Bethea, H.N.; Liu, J.
Using engineered 2-O-sulfotransferase to determine the activity of heparan sulfate C5-epimerase and its mutants
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Reijmers, R.M.; Vondenhoff, M.F.; Roozendaal, R.; Kuil, A.; Li, J.P.; Spaargaren, M.; Pals, S.T.; Mebius, R.E.
Impaired lymphoid organ development in mice lacking the heparan sulfate modifying enzyme glucuronyl C5-epimerase
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Grigorieva, E.; Prudnikova, T.; Domanitskaya, N.; Mostovich, L.; Pavlova, T.; Kashuba, V.; Zabarovsky, E.
D-Glucuronyl C5-epimerase suppresses small-cell lung cancer cell proliferation in vitro and tumour growth in vivo
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Occurrence of L-iduronic acid and putative D-glucuronyl C5-epimerases in prokaryotes
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Heterogeneity of D-glucuronyl C5-epimerase expression and epigenetic regulation in prostate cancer
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2013
Homo sapiens
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Sheng, J.; Xu, Y.; Dulaney, S.B.; Huang, X.; Liu, J.
Uncovering biphasic catalytic mode of C5-epimerase in heparan sulfate biosynthesis
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2012
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A novel bacterial enzyme with D-glucuronyl C5-epimerase activity
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Dejima, K.; Takemura, M.; Nakato, E.; Peterson, J.; Hayashi, Y.; Kinoshita-Toyoda, A.; Toyoda, H.; Nakato, H.
Analysis of Drosophila glucuronyl C5-epimerase: implications for developmental roles of heparan sulfate sulfation compensation and 2-O-sulfated glucuronic acid
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Drosophila melanogaster
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High cell density cultivation of recombinant Escherichia coli strains expressing 2-O-sulfotransferase and C5-epimerase for the production of bioengineered heparin
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Mochizuki, H.; Yamagishi, K.; Suzuki, K.; Kim, Y.S.; Kimata, K.
Heparosan-glucuronate 5-epimerase molecular cloning and characterization of a novel enzyme
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Structural and functional study of D-glucuronyl C5-epimerase
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Heparan sulfate biosynthetic system is inhibited in human glioma due to EXT1/2 and HS6ST1/2 down-regulation
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Homo sapiens (O94923)
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