{PDOC51275}
{PS51275; PEPTIDASE_C26_GGH}
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* Gamma-glutamyl hydrolase domain profile *
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Gamma-glutamyl  hydrolase  (GGH)  (EC 3.4.19.9)  is  an  enzyme  that  cleaves
gamma-linked    glutamyl    bonds.    With   a   substrate   such   as   folyl
penta-gamma-glutamate,  the  enzyme acts as an endopeptidase. GGH is a central
enzyme  in  the  metabolism of folic acid and antifolyl poly-gamma-glutamates.
Folate  is  an  essential  co-factor  of  enzymes  for the biosynthesis of DNA
precursors  and  several  amino acids. In mammals, the activity of GGH against
antifolate  drugs  is  involved in resistance to anticancer therapy. Mammalian
GGH  is  located  in  the lysosomes and in plants the enzyme is located in the
vacuoles.

The  3-dimensional structure of GGH shows a central eight-stranded beta-sheet,
which  is  sandwiched  by  three  and  five  alpha-helices  on  each side (see
<PDB:1L9X>).  The  fold resembles that of glutamine amidotransferases (GATase)
of  class  I,  which  are characterized by a conserved Cys-His-Glu active site
(see  <PDOC00405>).  The major differences consist of extensions in four loops
and  at the C-terminus of GGH [1]. The active site residues are well conserved
and  the  catalytically essential cysteine, positioned at a nucleophile elbow,
suggests  that  GGH  is  a  cysteine  peptidase. The gamma-glutamyl hydrolases
belong to the peptidase C26 family, which is classified with the peptidase C56
PfpI endopeptidases (see <PDOC51276>) in the clan PC(C) [E1, E2].

The profile we developed covers the entire gamma-glutamyl hydrolase domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Note: These proteins belong to family C26 in the classification of peptidases
 [E1,E2].
-Note:  The  gamma-glutamyl  hydrolase domain profile is in competition with a
 profile of a related domain, i.e. GATase type 1 (see <PDOC00405>).

-Last update: December 2006 / First entry.

[ 1] Li H., Ryan T.J., Chave K.J., Van Roey P.
     "Three-dimensional structure of human gamma -glutamyl hydrolase. A
     class I glutamine amidotransferase adapted for a complex substate."
     J. Biol. Chem. 277:24522-24529(2002).
     PubMed=11953431; DOI=10.1074/jbc.M202020200
[E1] https://www.uniprot.org/docs/peptidas
[E2] https://www.ebi.ac.uk/merops/cgi-bin/merops.cgi?id=C26

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