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Article Dans Une Revue ACS Catalysis Année : 2023

Substrate-Assisted Mechanism for the Degradation of N-glycans by a Gut Bacterial Mannoside Phosphorylase

Résumé

The unknown human gut bacterium mannoside phosphorylase (UhgbMP) is involved in the metabolization of eukaryotic N-glycans lining the intestinal epithelium, a factor associated with the onset and symptoms of inflammatory bowel diseases. In contrast with most glycoside phosphorylases, the putative catalytic acid of UhgbMP, Asp104, is far from the scissile glycosidic bond, challenging the classical Koshland mechanism. Using quantum mechanics/molecular mechanics metadynamics, we demonstrate that the enzyme operates by substrate-assisted catalysis via the 3-hydroxyl group of the mannosyl unit, following a 1S5/B2,5 → [B2,5]‡ → 0S2 conformational itinerary. Given the conservation of the active site hydrogen bond network across the family, this mechanism is expected to apply to other GH130 enzymes, as well as recently characterized mannoside phosphorylases with similar folds. Gaining insight into the catalytic reaction of these enzymes can aid the design of specific inhibitors to control interactions between gut microbes and the host.
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Dates et versions

hal-04213058 , version 1 (18-10-2023)

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Mercedes Alfonso-Prieto, Irene Cuxart, Gabrielle Potocki-Veronese, Isabelle André, Carme Rovira. Substrate-Assisted Mechanism for the Degradation of N-glycans by a Gut Bacterial Mannoside Phosphorylase. ACS Catalysis, 2023, 13 (7), pp.4283. ⟨10.1021/acscatal.3c00451⟩. ⟨hal-04213058⟩
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