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

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*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Enzymes active on glycosidic bonds are defined according to the stereochemistry of both substrates and products of the reactions they catalyse. The CAZy classification further assigns these enzymes into sequence-based families sharing a common stereochemistry for substrates (either α- or β-) and products, i.e. inverting or retaining mechanism. Here we describe the N-acetylgalactosaminidases AmGH109A and AmGH109B from the human gut symbiont Akkermansia muciniphila. Notably, AmGH109A displays α-retaining and β-inverting N-acetylgalactosaminidase activities with comparable efficiencies on natural disaccharides. This dual specificity could provide an advantage in targeting a broader range of host-derived glycans. We rationalise this discovery through bioinformatics, structural, mutational, and computational studies, unveiling a histidine residing in a conserved GGHGG motif as the elusive catalytic acidbase of the GH109 family. 
Original languageEnglish
JournalA C S Catalysis
Pages (from-to)3809-3819
Number of pages11
Publication statusPublished - 2020


  • Glycoside hydrolase
  • Human gut microbiota
  • Inverting mechanism
  • MD simulations
  • Mucin
  • Retaining

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