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

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.

Shuoker, BasharLund University,Technical University of Denmark (författare)
Chaberski, Evan KirkTechnical University of Denmark (författare)
Kunstmann, SonjaTechnical University of Denmark (författare)
Fredslund, FolmerTechnical University of Denmark(Swepub:lu)maxl-ffl (författare)
Nielsen, Tine SofieTechnical University of Denmark (författare)
Stender, Emil G.P.Technical University of Denmark (författare)
Peters, Günther H.J.Technical University of Denmark (författare)
Karlsson, Eva NordbergLund University,Lunds universitet,Bioteknik,Centrum för tillämpade biovetenskaper,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biotechnology,Center for Applied Life Sciences,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH(Swepub:lu)biot-eno (författare)
Welner, Ditte HededamTechnical University of Denmark (författare)
Hachem, Maher AbouTechnical University of Denmark(Swepub:lu)biot-mah (författare)
Technical University of DenmarkLund University (creator_code:org_t)

Ingår i:ACS Catalysis: American Chemical Society (ACS)10:6, s. 3809-38192155-5435

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