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Mechanistic insights into a Ca2+-dependent family of α-mannosidases in a human gut symbiont

Lookup NU author(s): Dr Claire Dumon, Emeritus Professor Harry Gilbert


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Colonic bacteria, exemplified by Bacteroides thetaiotaomicron, play a key role in maintaining human health by harnessing large families of glycoside hydrolases (GHs) to exploit dietary polysaccharides and host glycans as nutrients. Such GH family expansion is exemplified by the 23 family GH92 glycosidases encoded by the B. thetaiotaomicron genome. Here we show that these are alpha-mannosidases that act via a single displacement mechanism to utilize host N-glycans. The three-dimensional structure of two GH92 mannosidases defines a family of two-domain proteins in which the catalytic center is located at the domain interface, providing acid (glutamate) and base (aspartate) assistance to hydrolysis in a Ca2+-dependent manner. The three-dimensional structures of the GH92s in complex with inhibitors provide insight into the specificity, mechanism and conformational itinerary of catalysis. Ca2+ plays a key catalytic role in helping distort the mannoside away from its ground-state C-4(1) chair conformation toward the transition state.

Publication metadata

Author(s): Zhu YP, Suits MDL, Thompson AJ, Chavan S, Dinev Z, Dumon C, Smith N, Moremen KW, Xiang Y, Siriwardena A, Williams SJ, Gilbert HJ, Davies GJ

Publication type: Article

Publication status: Published

Journal: Nature Chemical Biology

Year: 2010

Volume: 6

Issue: 2

Pages: 125-132

Print publication date: 01/02/2010

ISSN (print): 1552-4450

ISSN (electronic): 1552-4469

Publisher: Nature Publishing Group


DOI: 10.1038/NCHEMBIO.278


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Funder referenceFunder name
Centre National de la Recherche Scientifique
Chinese Scholarship Council
Agence Nationale de Recherche sur le Sida et les Hepatities Virales (ANRS)
Department for Innovation, Universities and Skills (DIUS), UK, Newcastle University
European Molecular Biology Laboratory
Marie Curie European Reintegration, European Community
The Biotechnology and Biological Sciences Research Council of the UK
DK075322US National Institutes of Health
GM047533US National Institutes of Health
RR005351US National Institutes of Health