CATH Classification

Domain Context

CATH Clusters

Superfamily 1.10.246.130
Functional Family Gamma-glutamyltranspeptidase (Ggt)

Enzyme Information

3.4.19.13
Glutathione gamma-glutamate hydrolase.
based on mapping to UniProt P18956
(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.
2.3.2.2
Gamma-glutamyltransferase.
based on mapping to UniProt P18956
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.

UniProtKB Entries (1)

P18956
GGT_ECOLI
Escherichia coli K-12
Glutathione hydrolase proenzyme

PDB Structure

PDB 5B5T
External Links
Method X-RAY DIFFRACTION
Organism
Primary Citation
Phosphonate-based irreversible inhibitors of human gamma-glutamyl transpeptidase (GGT). GGsTop is a non-toxic and highly selective inhibitor with critical electrostatic interaction with an active-site residue Lys562 for enhanced inhibitory activity
Kamiyama, A., Nakajima, M., Han, L., Wada, K., Mizutani, M., Tabuchi, Y., Kojima-Yuasa, A., Matsui-Yuasa, I., Suzuki, H., Fukuyama, K., Watanabe, B., Hiratake, J.
Bioorg.Med.Chem.