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

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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. Enzymes fromglycoside hydrolase family GH109 are thus described as α retaining N-acetylgalactosaminidases.
Here we describe AmGH109A from the human gut symbiont Akkermansia muciniphila, which displays both α-retaining and β-inverting activities with comparable efficiencies on natural disaccharides, a dual specificity that 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 acid-base of the GH109 family.
Original languageEnglish
JournalChemRxiv
Number of pages24
DOIs
Publication statusSubmitted - 2019

Keywords

  • Glycoside hydrolase
  • Human gut microbiota
  • Inverting
  • Mechanism
  • MD simulations
  • Mucin
  • Retaining
  • Structure

Cite this

@article{2e1d692d29a2445bb45dc201cf19f764,
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",
abstract = "Enzymes active on glycosidic bonds are defined according to the stereochemistryof 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. Enzymes fromglycoside hydrolase family GH109 are thus described as α retaining N-acetylgalactosaminidases.Here we describe AmGH109A from the human gut symbiont Akkermansia muciniphila, which displays both α-retaining and β-inverting activities with comparable efficiencies on natural disaccharides, a dual specificity that 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 acid-base of the GH109 family.",
keywords = "Glycoside hydrolase, Human gut microbiota, Inverting, Mechanism, MD simulations, Mucin, Retaining, Structure",
author = "David Teze and Bashar Shuoker and Chaberski, {Evan Kirk} and Kunstmann, {Ruth Sonja} and Folmer Fredslund and Peters, {G{\"u}nther H.J.} and {Nordberg Karlsson}, Eva and Welner, {Ditte Hededam} and {Abou Hachem}, Maher",
year = "2019",
doi = "10.26434/chemrxiv.9989102.v1",
language = "English",
journal = "ChemRxiv",

}

TY - JOUR

T1 - 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

AU - Teze, David

AU - Shuoker, Bashar

AU - Chaberski, Evan Kirk

AU - Kunstmann, Ruth Sonja

AU - Fredslund, Folmer

AU - Peters, Günther H.J.

AU - Nordberg Karlsson, Eva

AU - Welner, Ditte Hededam

AU - Abou Hachem, Maher

PY - 2019

Y1 - 2019

N2 - Enzymes active on glycosidic bonds are defined according to the stereochemistryof 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. Enzymes fromglycoside hydrolase family GH109 are thus described as α retaining N-acetylgalactosaminidases.Here we describe AmGH109A from the human gut symbiont Akkermansia muciniphila, which displays both α-retaining and β-inverting activities with comparable efficiencies on natural disaccharides, a dual specificity that 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 acid-base of the GH109 family.

AB - Enzymes active on glycosidic bonds are defined according to the stereochemistryof 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. Enzymes fromglycoside hydrolase family GH109 are thus described as α retaining N-acetylgalactosaminidases.Here we describe AmGH109A from the human gut symbiont Akkermansia muciniphila, which displays both α-retaining and β-inverting activities with comparable efficiencies on natural disaccharides, a dual specificity that 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 acid-base of the GH109 family.

KW - Glycoside hydrolase

KW - Human gut microbiota

KW - Inverting

KW - Mechanism

KW - MD simulations

KW - Mucin

KW - Retaining

KW - Structure

U2 - 10.26434/chemrxiv.9989102.v1

DO - 10.26434/chemrxiv.9989102.v1

M3 - Journal article

JO - ChemRxiv

JF - ChemRxiv

ER -