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Joined 2026-09-21 Message
Incoming links: Claire Debarnot
Claire Debarnot 2026-11-05
Claire Debarnot is the first author of a 2019 structural study of human heparosan-N-sulfate-glucuronate 5-epimerase, an enzyme that modifies heparan sulfate. The reaction changes glucuronic acid residues into iduronic acid residues by epimerization at carbon five.[ref]
The team combined crystal structures with real-time nuclear magnetic resonance measurements. An inactive mutant could bind defined carbohydrate substrates and products, allowing their positions to be examined without rapid conversion obscuring the comparison. The structures showed a bent chain and constrained sugar-ring conformations at the active site.[ref]
Substrate binding mode and catalytic mechanism of human heparan sulfate d-glucuronyl C5 epimerase by Claire Debarnot and others. Abstract; Results, substrate/product complexes; Figures 1A and 2
This approach connects shape and chemical activity. Binding a carbohydrate does not establish that an enzyme catalyses its conversion; the independent activity measurement tested that distinction. Conversely, the bound structures helped explain which local arrangements accompany the reaction.
Heparosan-N-sulfate-glucuronate 5-epimerase 2026-11-05
Heparosan-N-sulfate-glucuronate 5-epimerase is an enzyme that converts selected D-glucuronate residues into L-iduronate within N-sulfated heparosan. This carbon-5 epimerization changes a stereocenter while preserving the number of sugar residues. The official classification is EC 5.1.3.17.[ref]
Heparosan-N-sulfate-glucuronate 5-epimerase in IUBMB Enzyme Nomenclature. Reaction and Comments
The surrounding chain is part of the substrate. Neighboring N-sulfated groups are required for recognition, and additional sulfate substitution can restrict the reaction. The enzyme should not therefore be described as simply acting on free glucuronate in any chemical setting.[ref]
Heparosan-N-sulfate-glucuronate 5-epimerase in IUBMB Enzyme Nomenclature. Comments, substrate context and exclusions
A 2019 study by Claire Debarnot and colleagues followed conversion with nuclear magnetic resonance using a carbon-13-labelled polymer. Under the reported conditions, the human enzyme approached approximately iduronate content. The researchers also compared site-directed mutagenesis variants: no activity was detected for two proposed catalytic-residue substitutions even at the stated higher enzyme concentration.[ref]
Substrate binding mode and catalytic mechanism of human heparan sulfate d-glucuronyl C5 epimerase by Claire Debarnot and others. Overall Structures of hGlce; Figure 1A and legend
For an illustrative 100 eligible sugar positions, a conversion gives 38 iduronate and 62 glucuronate positions, still 100 in total. The experiment changes chemical identity within a chain rather than extending it. The reported fraction belongs to specified conditions; it is not a universal composition of heparan sulfate.