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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

Teze, David ; Shuoker, Bashar ; Chaberski, Evan Kirk ; Kunstmann, Sonja ; Fredslund, Folmer LU ; Nielsen, Tine Sofie ; Stender, Emil G.P. ; Peters, Günther H.J. ; Karlsson, Eva Nordberg LU orcid and Welner, Ditte Hededam , et al. (2020) In ACS Catalysis 10(6). p.3809-3819
Abstract

Enzymes active on glycosidic bonds are defined according to the stereochemistry of both substrates and products of the reactions they catalyze. 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 (i.e., GH109: glycoside hydrolase family 109) 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... (More)

Enzymes active on glycosidic bonds are defined according to the stereochemistry of both substrates and products of the reactions they catalyze. 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 (i.e., GH109: glycoside hydrolase family 109) 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 rationalize this discovery through bioinformatics, structural, mutational, and computational studies, unveiling a histidine residing in a conserved GGHGG motif as the elusive catalytic acid-base of the GH109 family.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
GH4, glycoside hydrolase, human gut microbiota, inverting, MD simulations, mechanism, mucin, retaining
in
ACS Catalysis
volume
10
issue
6
pages
11 pages
publisher
The American Chemical Society (ACS)
external identifiers
  • scopus:85081646524
ISSN
2155-5435
DOI
10.1021/acscatal.9b04474
language
English
LU publication?
yes
id
bd29e90b-6378-4e06-86fc-09b423b3602b
date added to LUP
2020-04-14 15:33:56
date last changed
2023-04-24 14:19:35
@article{bd29e90b-6378-4e06-86fc-09b423b3602b,
  abstract     = {{<p>Enzymes active on glycosidic bonds are defined according to the stereochemistry of both substrates and products of the reactions they catalyze. 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 (i.e., GH109: glycoside hydrolase family 109) 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 rationalize this discovery through bioinformatics, structural, mutational, and computational studies, unveiling a histidine residing in a conserved GGHGG motif as the elusive catalytic acid-base of the GH109 family.</p>}},
  author       = {{Teze, David and Shuoker, Bashar and Chaberski, Evan Kirk and Kunstmann, Sonja and Fredslund, Folmer and Nielsen, Tine Sofie and Stender, Emil G.P. and Peters, Günther H.J. and Karlsson, Eva Nordberg and Welner, Ditte Hededam and Hachem, Maher Abou}},
  issn         = {{2155-5435}},
  keywords     = {{GH4; glycoside hydrolase; human gut microbiota; inverting; MD simulations; mechanism; mucin; retaining}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{6}},
  pages        = {{3809--3819}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{ACS Catalysis}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1021/acscatal.9b04474}},
  doi          = {{10.1021/acscatal.9b04474}},
  volume       = {{10}},
  year         = {{2020}},
}