Files
Document type
ArticleVersion
Accepted versionPublication date
All rights reserved
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/211468
Substrate-assisted mechanism for the degradation of n-glycans by a gut bacterial mannoside phosphorylase
Journal Title
Director/Tutor
Journal ISSN
Volume Title
Related resource
Abstract
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.
Subject (English)
Citation
Citation
ALFONSO PRIETO, Mercedes, et al. Substrate-assisted mechanism for the degradation of n-glycans by a gut bacterial mannoside phosphorylase. ACS Catalysis. 2023. Vol. 13, num. 7, pags. 4283-4289. ISSN 2155-5435. [consulted: 13 of August of 2026]. Available at: https://hdl.handle.net/2445/211468