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

70 Downloads (Pure)

Abstract

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
Volume10
Pages (from-to)3809-3819
Number of pages11
ISSN2155-5435
DOIs
Publication statusPublished - 2020

Keywords

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

Cite this