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TezeD and ShuokerB__GH109_ChemRxive.pdf (2.89 MB)

The Catalytic Acid-Base in GH109 Resides in a Conserved GGHGG Loop and Allows for Comparable α-Retaining and β-Inverting Activity in an N-Acetylgalactosaminidase from Akkermansia Muciniphila

submitted on 16.10.2019, 14:18 and posted on 21.10.2019, 20:49 by David Teze, Bashar Shuoker, Evan Kirk Chaberski, Ruth Sonja Kunstmann, Folmer Fredslund, Günther H.J. Peters, Eva Nordberg Karlsson, Ditte Hededam Welner, Maher Abou Hachem
The study describes the first glycoside hydrolase that exhibits comparable levels of activity on α- and β-linked saccharide substrates. This enzyme, assigned into GH109, is encoded by the genome of the human gut symbiont Akkermansia muciniphila that is a model primary degrader of the heavily O-glycosylated mucin glycoprotein that coats the epithelial enterocytes.The elusive catalytic acid/base catalyst in GH109 enzymes is identified as a histidine that is presented by a flexible loop that positions it for catalysis on both α- and β-substrates. This dual activity may be an evolutionary adaptation to extend the range of substrates targeted by a single non-canonical NAD+-dependant GH.


Ministry of higher education and scientific research of Iraq for a PhD stipend for Bashar Shuoker

The Novo Nordisk Foundation for a postdoctoral fellowship for David Teze (NNF17OC0025660)

European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie postdoc fellowship agreement No 713683 for Sonja Kunstmann

The Novo Nordisk Foundation for the grants NNF10CC1016517 and NNF16OC0019088 for Ditte Hededam Welner

The NMR spectra were recorded at the NMR Center DTU, supported by the Villum Foundation.

X-Ray data collection was supported by Danscatt


Email Address of Submitting Author


Technical University of Denmark, Department of Biotechnology and Biomedicine



ORCID For Submitting Author


Declaration of Conflict of Interest

No conflict of interests