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PROSITE documentation PDOC51275 [for PROSITE entry PS51275]

Gamma-glutamyl hydrolase domain profile





Description

γ-glutamyl hydrolase (GGH) (EC 3.4.19.9) is an enzyme that cleaves γ-linked glutamyl bonds. With a substrate such as folyl penta-γ-glutamate, the enzyme acts as an endopeptidase. GGH is a central enzyme in the metabolism of folic acid and antifolyl poly-γ-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 β-sheet, which is sandwiched by three and five α-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 γ-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 γ-glutamyl hydrolase domain.

Note:

These proteins belong to family C26 in the classification of peptidases [E1,E2].

Note:

The γ-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.

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Technical section

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

PEPTIDASE_C26_GGH, PS51275; Gamma-glutamyl hydrolase domain profile  (MATRIX)


References

1AuthorsLi H. Ryan T.J. Chave K.J. Van Roey P.
TitleThree-dimensional structure of human gamma -glutamyl hydrolase. A class I glutamine amidotransferase adapted for a complex substate.
SourceJ. Biol. Chem. 277:24522-24529(2002).
PubMed ID11953431
DOI10.1074/jbc.M202020200

E1Titlehttps://www.uniprot.org/docs/peptidas

E2Titlehttps://www.ebi.ac.uk/merops/cgi-bin/merops.cgi?id=C26



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