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Literature summary for 2.3.2.2 extracted from
- Probing the interactions of sulfur-containing histidine compounds with human gamma-glutamyl transpeptidase (2019), Mar. Drugs, 17, 650 .
Application
| Application | Comment | Organism |
|---|---|---|
| drug development | development of 5-thiohistidine derivatives as therapeutics for GGT-positive tumors | Homo sapiens |
| medicine | development of 5-thiohistidine derivatives as therapeutics for GGT-positive tumors | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| (2S)-2-amino-2-[(5S)-3-chloro-4,5-dihydro-1,2-oxazol-5-yl]acetic acid | i.e. acivicin | Equus caballus |  |
| (2S)-2-amino-2-[(5S)-3-chloro-4,5-dihydro-1,2-oxazol-5-yl]acetic acid | i.e. acivicin | Homo sapiens | |
| 5-thiohistidine | 50% inhibition at 0.015 mM, mechanism of 5-thio driven inhibition of GGT, overview. Reversible inhibition mechanism | Equus caballus | |
| 5-thiohistidine | mechanism of 5-thio driven inhibition of GGT, overview | Homo sapiens | |
| 6-diazo-5-oxo-L-norleucine | i.e. DON, irreversible inhibition 50% inhibition at 0.282 mM | Equus caballus | |
| 6-diazo-5-oxo-L-norleucine | i.e. DON, irreversible inhibition | Homo sapiens | |
| ergothioneine | a natural trimethyl-2-thiohistidine, 50% inhibition at 0.297 mM. Reversible inhibition mechanism | Equus caballus | |
| ergothioneine | a natural trimethyl-2-thiohistidine, reversible inhibition mechanism | Homo sapiens | |
| additional information | identification of ovothiols, 5(NPi)-methyl-thiohistidines of marine origin, as non-competitive-like inhibitors of GGT that are more potent than the GGT inhibitor, 6-diazo-5-oxo-L-norleucine (DON). Interactions of 5-thiohistidines with enzyme GGT by molecular docking analysis and comparison with ergothioneine (a natural trimethyl-2-thiohistidine), physiological substrate glutathione, and DON inhibitor, overview. No inhibition by DTT | Equus caballus | |
| additional information | identification of ovothiols, 5(NPi)-methyl-thiohistidines of marine origin, as non-competitive-like inhibitors of GGT that are more potent than the GGT inhibitor, 6-diazo-5-oxo-L-norleucine (DON), and are not toxic for human embryonic cells. Interactions of 5-thiohistidines with enzyme GGT by molecular docking analysis and comparison with ergothioneine (a natural trimethyl-2-thiohistidine), physiological substrate glutathione, and DON inhibitor, overview. No inhibition by DTT | Homo sapiens | |
| O-diazoacetyl-L-serine | i.e. azaserine | Equus caballus | |
| O-diazoacetyl-L-serine | i.e. azaserine | Homo sapiens | |
| ovothiol A | noncompetitive inhibition, 50% inhibition at 0.016 mM | Equus caballus | |
| ovothiol A | noncompetitive inhibition, reversible inhibition mechanism | Homo sapiens | |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | Michaelis-Menten kinetics | Equus caballus | |
| 0.007 | - |
glycylglycine | pH 7.4, 37°C | Equus caballus | |
| 0.021 | - |
L-gamma-glutamyl-4-nitroanilide | pH 7.4, 37°C | Equus caballus | |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cell surface | - |
Homo sapiens | 9986 | - |
| cell surface | - |
Equus caballus | 9986 | - |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| a (5-L-glutamyl)-peptide + an amino acid | Homo sapiens | - |
a peptide + a 5-L-glutamyl amino acid | - |
? | |
| a (5-L-glutamyl)-peptide + an amino acid | Equus caballus | - |
a peptide + a 5-L-glutamyl amino acid | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Equus caballus | E5G727 | GGT1 | - |
| Homo sapiens | P19440 | GGT1 | - |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| commercial preparation | kidney enzyme | Equus caballus | - |
| HEK-293 cell | - |
Homo sapiens | - |
| kidney | - |
Equus caballus | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| a (5-L-glutamyl)-peptide + an amino acid | - |
Homo sapiens | a peptide + a 5-L-glutamyl amino acid | - |
? | |
| a (5-L-glutamyl)-peptide + an amino acid | - |
Equus caballus | a peptide + a 5-L-glutamyl amino acid | - |
? | |
| L-gamma-glutamyl-4-nitroanilide + glycylglycine | - |
Homo sapiens | 4-nitroaniline + 5-L-glutamyl-glycylglycine | - |
? | |
| L-gamma-glutamyl-4-nitroanilide + glycylglycine | - |
Equus caballus | 4-nitroaniline + 5-L-glutamyl-glycylglycine | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| eqGGT | - |
Equus caballus |
| gamma-glutamyl transpeptidase | - |
Homo sapiens |
| gamma-glutamyl transpeptidase | - |
Equus caballus |
| GGT | - |
Homo sapiens |
| GGT | - |
Equus caballus |
| HGGT | - |
Homo sapiens |
| More | cf. EC 3.4.19.13 | Homo sapiens |
| More | cf. EC 3.4.19.13 | Equus caballus |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 37 | - |
assay at | Homo sapiens |
| 37 | - |
assay at | Equus caballus |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7.4 | - |
assay at | Homo sapiens |
| 7.4 | - |
assay at | Equus caballus |
Ki Value [mM]
| Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | inhibition kinetics | Equus caballus | |
| 0.007 | - |
ovothiol A | versus L-gamma-glutamyl-4-nitroanilide, pH 7.4, 37°C | Equus caballus | |
| 0.021 | - |
ovothiol A | versus glycylglycine, pH 7.4, 37°C | Equus caballus | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| additional information | catalytic mechanism of human GGT, catalytic Thr381 within the active site, acts as a nucleophile and attacks the delta-carbon of the glutamate moiety, leading to the formation of a tetrahedral intermediate (gamma-glutamyl enzyme complex), stabilized by two conserved glycines (Gly473 and Gly474 in hGGT), overview | Homo sapiens |
| physiological function | gamma-glutamyl transpeptidase (GGT) is a cell surface enzyme involved in glutathione metabolism and maintenance of redox homeostasis. High expression of GGT on tumor cells is associated with an increase of cell proliferation and resistance against chemotherapy. GGT catalyzes the cleavage of gamma-glutamyl compounds and the transfer of the gamma-glutamyl group to an acceptor substrate by a ping-pong mechanism. GSH, the most common physiological substrate of GGT, acts as the gamma-glutamyl donor in the initial reaction of hydrolysis (EC 3.4.19.13) | Homo sapiens |
| physiological function | gamma-glutamyl transpeptidase (GGT) is a cell surface enzyme involved in glutathione metabolism and maintenance of redox homeostasis. High expression of GGT on tumor cells is associated with an increase of cell proliferation and resistance against chemotherapy. GGT catalyzes the cleavage of gamma-glutamyl compounds and the transfer of the gamma-glutamyl group to an acceptor substrate by a ping-pong mechanism. GSH, the most common physiological substrate of GGT, acts as the gamma-glutamyl donor in the initial reaction of hydrolysis (EC 3.4.19.13) | Equus caballus |
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