PROSITE documentation PDOC52009
Glycosyl hydrolases family 84 (GH84) domain profile


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.

Last update:

November 2022 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

GH84, PS52009; Glycosyl hydrolases family 84 (GH84) domain profile  (MATRIX)


1AuthorsCetinbas N. Macauley M.S. Stubbs K.A. Drapala R. Vocadlo D.J.
TitleIdentification of Asp174 and Asp175 as the key catalytic residues of human O-GlcNAcase by functional analysis of site-directed mutants.
SourceBiochemistry 45:3835-3844(2006).
PubMed ID16533067

2AuthorsDennis R.J. Taylor E.J. Macauley M.S. Stubbs K.A. Turkenburg J.P. Hart S.J. Black G.N. Vocadlo D.J. Davies G.J.
TitleStructure and mechanism of a bacterial beta-glucosaminidase having O-GlcNAcase activity.
SourceNat. Struct. Mol. Biol. 13:365-371(2006).
PubMed ID16565725

3AuthorsRao F.V. Dorfmueller H.C. Villa F. Allwood M. Eggleston I.M. van Aalten D.M.F.
TitleStructural insights into the mechanism and inhibition of eukaryotic O-GlcNAc hydrolysis.
SourceEMBO. J. 25:1569-1578(2006).
PubMed ID16541109

4AuthorsOstrowski A. Gundogdu M. Ferenbach A.T. Lebedev A.A. van Aalten D.M.F.
TitleEvidence for a Functional O-Linked N-Acetylglucosamine (O-GlcNAc) System in the Thermophilic Bacterium Thermobaculum terrenum.
SourceJ. Biol. Chem. 290:30291-30305(2015).
PubMed ID26491011

5AuthorsLi B. Li H. Lu L. Jiang J.
TitleStructures of human O-GlcNAcase and its complexes reveal a new substrate recognition mode.
SourceNat. Struct. Mol. Biol. 24:362-369(2017).
PubMed ID28319083

6AuthorsRoth C. Chan S. Offen W.A. Hemsworth G.R. Willems L.I. King D.T. Varghese V. Britton R. Vocadlo D.J. Davies G.J.
TitleStructural and functional insight into human O-GlcNAcase.
SourceNat. Chem. Biol. 13:610-612(2017).
PubMed ID28346405

7AuthorsPluvinage B. Massel P.M. Burak K. Boraston A.B.
TitleStructural and functional analysis of four family 84 glycoside hydrolases from the opportunistic pathogen Clostridium perfringens.
SourceGlycobiology 30:49-57(2019).
PubMed ID31701135



PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.


View entry in original PROSITE document format
View entry in raw text format (no links)