Glycoside hydrolases (GHs, EC 3.2.1.-) form a widespread group of enzymes that hydrolyze the glycoside bond between monosaccharide units or between a carbohydrate and an aglycone moiety. GHs can act specifically as exo-cleaving enzymes to remove the sugar units from the ends of chains and release small sugar products, or endo-cleaving enzymes to act within the polysaccharide chain and produce oligosaccharides. Family 84 glycoside hydrolases (GH84) cleave the glycosidic linkage of N-acetylglucosaminides by a two-step catalytic mechanism that involves a pair of aspartate residues as catalytic residues, D1 as the polarizing residue and Asp175 as the general acid/base catalyst [E1,E2]. The GH84 catalytic domain is found both in eukaryotic and prokaryotic proteins:

• Mammalian O-GlcNAcase (OGA).
• Bacterial O-GlcNAcase (OGA).
• Clostridium perfringens NagH, NagI, NagJ and NagK proteins, act as β-N- acetyl-D-glucosaminidases able to hydrolyze N- and O-glycan motifs. In addition to the GH84 catalytic modules, all four enzymes contain a combination of ancillary modules, such as family 32 carbohydrate-binding (CBM32s), found-in-various-architectures (FIVAR), fibronectin-like type III (FN3) (see <PDOC50853>), cohesin (X82) and/or Dockerin (Doc) (see <PDOC51766>) modules, as well as uncharacterized modules.

The GH84 catalytic domain consists of a classic (β/α)8-barrel (eight-stranded parallel β-sheet core mainly surrounded by eight α-helices), which forms a deep pocket for GlcNAc binding and hydrolysis (see <PDB:5TKE>) [1,2,3,4,5,6,7].

The profile we developed covers the whole GH84 catalytic domain.