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

The study describes the first glycoside hydrolase that exhibits comparable levels of activity on α- and β-linked saccharide substrates. This enzyme, assigned into GH109, is encoded by the genome of the human gut symbiont Akkermansia muciniphila that is a model primary degrader of the heavily O-glycosylated mucin glycoprotein that coats the epithelial enterocytes.The elusive catalytic acid/base catalyst in GH109 enzymes is identified as a histidine that is presented by a flexible loop that positions it for catalysis on both α- and β-substrates. This dual activity may be an evolutionary adaptation to extend the range of substrates targeted by a single non-canonical NAD+-dependant GH.