CATH Classification

Domain Context

CATH Clusters

Superfamily 1.10.246.130
Functional Family glutathione hydrolase 1 proenzyme

Enzyme Information

2.3.2.2
Gamma-glutamyltransferase.
based on mapping to UniProt P19440
A (5-L-glutamyl)-peptide + an amino acid = a peptide + a 5-L-glutamyl amino acid.
-!- The mammlian enzyme is part of the cell antioxidant defense mechanism. -!- It initiates extracellular glutathione (GSH) breakdown, provides cells with a local cysteine supply and contributes to maintain intracelular GSH levels. -!- The protein also has EC 3.4.19.13 activity. -!- The enzyme consists of two chains that are created by the proteolytic cleavage of a single precursor polypeptide. -!- The N-terminal L-threonine of the C-terminal subunit functions as the active site for both the cleavage and the hydrolysis reactions.
3.4.19.14
Leukotriene-C(4) hydrolase.
based on mapping to UniProt P19440
Leukotriene C(4) + H(2)O = leukotriene D(4) + L-glutamate.
-!- The mouse enzyme is specific for leukotriene C(4), while the human enzyme also has considerable activity toward glutathione and oxidized glutathione (cf. EC 3.4.19.13).
3.4.19.13
Glutathione gamma-glutamate hydrolase.
based on mapping to UniProt P19440
(1) Glutathione + H(2)O = L-cysteinylglycine + L-glutamate. (2) A glutathione-S-conjugate + H(2)O = an (L-cysteinylglycine)-S- conjugate + L-glutamate.
-!- This is a bifunctional protein that also has the activity of EC 2.3.2.2. -!- The enzyme binds its substrate by forming an initial gamma-glutamyl- enzyme intermediate, releasing the L-cysteinylglycine part of the molecule. -!- The enzyme then reacts with either a water molecule or a different acceptor substrate (usually an L-amino acid or a dipeptide) to form L-glutamate or a product containing a new gamma-glutamyl isopeptide bond, respectively. -!- The enzyme acts on glutathione, glutathione-S-conjugates, and, at a lower level, on other substrates with an N-terminal L-gamma-glutamyl residue. -!- It plays a crucial part in the glutathione-mediated xenobiotic detoxification pathway. -!- The enzyme consists of two chains that are created by the proteolytic cleavage of a single precursor polypeptide.

UniProtKB Entries (1)

P19440
GGT1_HUMAN
Homo sapiens
Glutathione hydrolase 1 proenzyme

PDB Structure

PDB 5V4Q
External Links
Method X-RAY DIFFRACTION
Organism
Primary Citation
Structure of 6-diazo-5-oxo-norleucine-bound human gamma-glutamyl transpeptidase 1, a novel mechanism of inactivation.
Terzyan, S.S., Cook, P.F., Heroux, A., Hanigan, M.H.
Protein Sci.