Journal article
Mechanistic insights into a Ca2 -dependent family of α-mannosidases in a human gut symbiont
Y Zhu, MDL Suits, AJ Thompson, S Chavan, Z Dinev, C Dumon, N Smith, KW Moremen, Y Xiang, A Siriwardena, SJ Williams, HJ Gilbert, GJ Davies
Nature Chemical Biology | NATURE PORTFOLIO | Published : 2010
DOI: 10.1038/nchembio.278
Abstract
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 α-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..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank S. Withers (University of British Columbia) for compound 9. The Biotechnology and Biological Sciences Research Council of the UK is thanked for funding. M. D. L. S. is a European Molecular Biology Laboratory long-term fellowship holder, and G. J. D. is a Royal Society/Wolfson Research Merit Award recipient. C. D. was supported by a Marie Curie European Reintegration grant within the 7th European Community Framework Programme. Y. Z. is supported by the Department for Innovation, Universities and Skills (DIUS), UK, Newcastle University and the Chinese Scholarship Council. S. J. W. thanks the Australian Research Council for funding support. K. W. M. acknowledges the support of US National Institutes of Health grants GM047533, RR005351 and DK075322. S. C. is supported by a postdoctoral fellowship from the Agence Nationale de Recherche sur le Sida et les Hepatities Virales (ANRS). A. S. is supported by Centre National de la Recherche Scientifique.