PROSITE documentation PDOC52009Glycosyl 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.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Cetinbas N. Macauley M.S. Stubbs K.A. Drapala R. Vocadlo D.J. |
| Title | Identification of Asp174 and Asp175 as the key catalytic residues of human O-GlcNAcase by functional analysis of site-directed mutants. | |
| Source | Biochemistry 45:3835-3844(2006). | |
| PubMed ID | 16533067 | |
| DOI | 10.1021/bi052370b |
| 2 | Authors | Dennis 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. |
| Title | Structure and mechanism of a bacterial beta-glucosaminidase having O-GlcNAcase activity. | |
| Source | Nat. Struct. Mol. Biol. 13:365-371(2006). | |
| PubMed ID | 16565725 | |
| DOI | 10.1038/nsmb1079 |
| 3 | Authors | Rao F.V. Dorfmueller H.C. Villa F. Allwood M. Eggleston I.M. van Aalten D.M.F. |
| Title | Structural insights into the mechanism and inhibition of eukaryotic O-GlcNAc hydrolysis. | |
| Source | EMBO. J. 25:1569-1578(2006). | |
| PubMed ID | 16541109 | |
| DOI | 10.1038/sj.emboj.7601026 |
| 4 | Authors | Ostrowski A. Gundogdu M. Ferenbach A.T. Lebedev A.A. van Aalten D.M.F. |
| Title | Evidence for a Functional O-Linked N-Acetylglucosamine (O-GlcNAc) System in the Thermophilic Bacterium Thermobaculum terrenum. | |
| Source | J. Biol. Chem. 290:30291-30305(2015). | |
| PubMed ID | 26491011 | |
| DOI | 10.1074/jbc.M115.689596 |
| 5 | Authors | Li B. Li H. Lu L. Jiang J. |
| Title | Structures of human O-GlcNAcase and its complexes reveal a new substrate recognition mode. | |
| Source | Nat. Struct. Mol. Biol. 24:362-369(2017). | |
| PubMed ID | 28319083 | |
| DOI | 10.1038/nsmb.3390 |
| 6 | Authors | Roth 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. |
| Title | Structural and functional insight into human O-GlcNAcase. | |
| Source | Nat. Chem. Biol. 13:610-612(2017). | |
| PubMed ID | 28346405 | |
| DOI | 10.1038/nchembio.2358 |
| 7 | Authors | Pluvinage B. Massel P.M. Burak K. Boraston A.B. |
| Title | Structural and functional analysis of four family 84 glycoside hydrolases from the opportunistic pathogen Clostridium perfringens. | |
| Source | Glycobiology 30:49-57(2019). | |
| PubMed ID | 31701135 | |
| DOI | 10.1093/glycob/cwz069 |
| E1 | Source | http://www.cazy.org/GH84.html |
| E2 | Title | https://www.cazypedia.org/index.php/Glycoside_Hydrolase_Family_84 |
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