Reaction: Epimerization of D-glucuronate in heparosan-N-sulfate to L-iduronate.
Other name(s): heparosan epimerase; heparosan-N-sulfate-D-glucuronosyl 5-epimerase; C-5 uronosyl epimerase; polyglucuronate epimerase; D-glucuronyl C-5 epimerase; poly[(1,4)-β-D-glucuronosyl-(1,4)-N-sulfo-α-D-glucosaminyl] glucurono-5-epimerase
Systematic name: poly[(1→4)-β-D-glucuronosyl-(1→4)-N-sulfo-α-D-glucosaminyl] glucurono-5-epimerase
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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 112567-86-9
References:
1. Jacobsson, I., Bäckström, G., Höök, M., Lindahl, U., Feingold, D.S., Malmström, A. and Rodén, L. Biosynthesis of heparin. Assay and properties of the microsomal uronosyl C-5 epimerase. J. Biol. Chem. 254 (1979) 2975-2982. [PMID: 107165]
2. Jacobsson, I., Lindahl, U., Jensen, J.W., Roden, L., Prihar, H. and Feingold, D.S. Biosynthesis of heparin. Substrate specificity of heparosan N-sulfate D-glucuronosyl 5-epimerase. J. Biol. Chem. 259 (1984) 1056-1063. [PMID: 6420398]
3. Hagner-McWhirter, A., Hannesson, H.H., Campbell, P., Westley, J., Roden, L., Lindahl, U. and Li, J.P. 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. Glycobiology 10 (2000) 159-171. [PMID: 10642607]