Journal Article

FZJ-2023-01491

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Substrate-Assisted Mechanism for the Degradation of N -Glycans by a Gut Bacterial Mannoside Phosphorylase

Alfonso-Prieto, M.FZJ* ; Cuxart, I. ; Potocki-Véronèse, G. ; André, I. (Corresponding author) ; Rovira, C. (Corresponding author)

2023
ACS Washington, DC

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Please use a persistent id in citations: http://hdl.handle.net/2128/34140  doi:10.1021/acscatal.3c00451

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.

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Contributing Institute(s):

1. Computational Biomedicine (IAS-5)
2. Computational Biomedicine (INM-9)

Research Program(s):

1. 5241 - Molecular Information Processing in Cellular Systems (POF4-524) (POF4-524)

Appears in the scientific report 2023

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Database coverage:
; ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; IF >= 10 ; JCR ; SCOPUS ; Web of Science Core Collection

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