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.
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