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.
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.
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
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
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
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
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
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
Biosynthesis of heparin/heparan sulfate: kinetic studies of the glucuronyl C5-epimerase with N-sulfated derivatives of the Escherichia coli K5 capsular polysaccharide as substrates.
decreased GLCE expression is observed in 10% of benign prostate hyperplasia tissues and 53% of prostate tumors, and increased GLCE mRNA levels are detected in 49% of benign prostate hyperplasia tissues and 21% of tumors, intratumoral heterogeneity of GLCE protein levels both in benign prostate hyperplasia and prostate cancer cells, resulting in a mixed population of GLCE-expressing and nonexpressing epithelial cells in vivo
decreased GLCE expression is observed in 10% of benign prostate hyperplasia tissues and 53% of prostate tumors, and increased GLCE mRNA levels are detected in 49% of benign prostate hyperplasia tissues and 21% of tumors, intratumoral heterogeneity of GLCE protein levels both in benign prostate hyperplasia and prostate cancer cells, resulting in a mixed population of GLCE-expressing and nonexpressing epithelial cells in vivo
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
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
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
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
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
the human epimerase is a 617-amino acid protein that consists of three domains, cytoplasmic comprising residues Met1-Lys11, transmembrane with Thr12-Trp28, and catalytic domain formed by Asn29-Asn617
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
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
enzyme GLCE is ectopically re-expressed in morphologically different LNCaP and PC3 prostate cancer cells, quantitative real-time PCR enzyme expression analysis
the overall transcriptional activity of the main heparan sulfate biosynthesis-involved genes (EXT1, EXT2, NDST1, NDST2, GLCE, HS2ST1, HS3ST1, HS3ST2, HS6ST1, HS6ST2, SULF1, SULF2, HPSE) is decreased by 1.5-2fold in Grade II-III glioma (p < 0.01) and by 3fold in Grade IV glioma (glioblastoma multiforme, GBM) (p < 0.05), as compared with the para-tumourous tissue
GLCE upregulation plus expression pattern of a panel of six genes, discriminating morphologically different prostate cancer cell subtypes, is a potential marker of aggressive prostate cancer
the anti-tumour effects associated with ectopic GLCE re-expression suggest that it may be a potential tumour-suppressor gene and a possible target for lung cancer diagnosis and treatment
the enzyme, coexpressed with 2-O-sulfotransferase in bacteria, can be used for production of bioengineered heparin as a potential substitute for the animal-sourced anticoagulant drug
in 82-84% of human breast tumors there is either downregulation or loss of D-glucuronyl C5-epimerase mRNA expression and significant decrease of the protein content. In 77% of cases, GLCE expression is decreased also in the normal-appearing tissue surrounding the tumor node but the protein amount is comparable to normal breast tissue
Zhang, J.; Suflita, M.; Li, G.; Zhong, W.; Li, L.; Dordick, J.S.; Linhardt, R.J.; Zhang, F.
High cell density cultivation of recombinant Escherichia coli strains expressing 2-O-sulfotransferase and C5-epimerase for the production of bioengineered heparin