Journal article
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
Section for Protein Chemistry and Enzyme Technology, Department of Biotechnology and Biomedicine, Technical University of Denmark1
Enzyme and Protein Chemistry, Section for Protein Chemistry and Enzyme Technology, Department of Biotechnology and Biomedicine, Technical University of Denmark2
Department of Biotechnology and Biomedicine, Technical University of Denmark3
Enzyme Engineering & Structural Biology, Research Groups, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark4
Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark5
Department of Chemistry, Technical University of Denmark6
Protein Glycoscience and Biotechnology, Section for Protein Chemistry and Enzyme Technology, Department of Biotechnology and Biomedicine, Technical University of Denmark7
Enzyme Technology, Section for Protein Chemistry and Enzyme Technology, Department of Biotechnology and Biomedicine, Technical University of Denmark8
Lund University9
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.
| Language: | English |
|---|---|
| Year: | 2020 |
| Pages: | 3809-3819 |
| ISSN: | 21555435 |
| Types: | Journal article |
| DOI: | 10.26434/chemrxiv.9989102.v1 |
| ORCIDs: | Teze, David , Kunstmann, Sonja , Fredslund, Folmer , Stender, Emil G. P. , Peters, Günther H.J. , Welner, Ditte Hededam and Abou Hachem, Maher |
Glycoside hydrolase Human gut microbiota Inverting mechanism MD simulations Mucin Retaining
