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 language | English |
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Journal | A C S Catalysis |
Volume | 10 |
Pages (from-to) | 3809-3819 |
Number of pages | 11 |
ISSN | 2155-5435 |
DOIs | |
Publication status | Published - 2020 |
Keywords
- Glycoside hydrolase
- Human gut microbiota
- Inverting mechanism
- MD simulations
- Mucin
- Retaining