{PDOC52009}
{PS52009; GH84}
{BEGIN}
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* Glycosyl hydrolases family 84 (GH84) domain profile *
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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 beta-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 (beta/alpha)8-barrel (eight-
stranded parallel  beta-sheet  core mainly surrounded by eight alpha-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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: November 2022 / First entry.

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

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