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@ARTICLE{AlfonsoPrieto:1005471,
author = {Alfonso-Prieto, Mercedes and Cuxart, Irene and
Potocki-Véronèse, Gabrielle and André, Isabelle and
Rovira, Carme},
title = {{S}ubstrate-{A}ssisted {M}echanism for the {D}egradation of
{N} -{G}lycans by a {G}ut {B}acterial {M}annoside
{P}hosphorylase},
journal = {ACS catalysis},
volume = {13},
issn = {2155-5435},
address = {Washington, DC},
publisher = {ACS},
reportid = {FZJ-2023-01491},
pages = {4283 - 4289},
year = {2023},
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.},
cin = {IAS-5 / INM-9},
ddc = {540},
cid = {I:(DE-Juel1)IAS-5-20120330 / I:(DE-Juel1)INM-9-20140121},
pnm = {5241 - Molecular Information Processing in Cellular Systems
(POF4-524)},
pid = {G:(DE-HGF)POF4-5241},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000953970600001},
doi = {10.1021/acscatal.3c00451},
url = {https://juser.fz-juelich.de/record/1005471},
}