Cloned (Comment) | Organism |
---|---|
isozymes GSTP1-1 and GSTM2-2, expression in Escherichia coli | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
1-chloro-2,4-dinitrobenzene | competitive inhibition by the substrate | Homo sapiens | |
4-(acryloylamino)-N-(5-[[5-([5-[(2-carbamimidamidoethyl)carbamoyl]-1-methyl-1H-pyrrol-3-yl]carbamoyl)-1-methyl-1H-pyrrol-3-yl]carbamoyl]-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide | a brostallicin derivative, the debrominated derivative of brostallicin is almost completely ineffective as an inhibitor of GSTP1-1 | Homo sapiens | |
4-[(2-bromoacryloyl)amino]-N-(5-[[5-([5-[(2-carbamimidamidoethyl)carbamoyl]-1-methyl-1H-pyrrol-3-yl]carbamoyl)-1-methyl-1H-pyrrol-3-yl]carbamoyl]-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide | i.e. brostallicin, mixed-type inhibition, inhibits GSTP1-1 and GSTM2-2, thereby being much more efficient in inhibiting GSTM2-2 than in inhibiting GSTP1-1. Brostallicin sensitivity for brostallicin is higher in cells overexpressing either the GST-pi or the GST-mu gene | Homo sapiens | |
glutathione | competitive inhibition by the substrate | Homo sapiens | |
L-g-glutamyl-S-[3-([5-[(5-[[5-([5-[(2-carbamimidamidoethyl)carbamoyl]-1-methyl-1H-pyrrol-3-yl]carbamoyl)-1-methyl-1H-pyrrol-3-yl]carbamoyl]-1-methyl-1H-pyrrol-3-yl)carbamoyl]-1-methyl-1H-pyrrol-3-yl]amino)-2-hydroxy-3-oxopropyl]-L-cysteinylglycine | a brostallicin derivative, inhibits GSTP1-1 and GSTM2-2 | Homo sapiens | |
L-g-glutamyl-S-[3-([5-[(5-[[5-([5-[(2-carbamimidamidoethyl)carbamoyl]-1-methyl-1H-pyrrol-3-yl]carbamoyl)-1-methyl-1H-pyrrol-3-yl]carbamoyl]-1-methyl-1H-pyrrol-3-yl)carbamoyl]-1-methyl-1H-pyrrol-3-yl]amino)-3-oxo-2-(phosphonooxy)propyl]-L-cysteinylglycine | a brostallicin derivative, inhibits GSTP1-1 and GSTM2-2 | Homo sapiens |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | kinetic analysis, overview. GSTM2-2 does not follow a rapid equilibrium Michaelis-Menten mechanism. However, the low catalytic activity of the GSTM2-2 isoenzyme and its high affinity for brostallicin prevent an accurate kinetic study | Homo sapiens | |
0.005 | - |
brostallicin | pH 6.5, 25°C, GSTM2-2 | Homo sapiens | |
4.5 | - |
glutathione | pH 6.5, 25°C, GSTM2-2 | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
brostallicin + glutathione | Homo sapiens | involved in activation of the prodrug, mechanism, overview. The reaction proceeds via the alpha-chloroamido derivative of the GSH-brostallicin adduct, is able to alkylate DNA in a sequence-specific manner and appears to be the active form of the drug, brostallicin cytotoxicity of brostallicin is higher in cells overexpressing either the GST-pi or the GST-mu gene | glutathionyl-brostallicin | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Purification (Comment) | Organism |
---|---|
recombinant isozymes GSTP1-1 and GSTM2-2 from Escherichia coli | Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
MCF-7 cell | a breast carcinoma cell line with GSTP1-1 and GSTM2-2 as the predominant GST isoenzymes | Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
brostallicin + glutathione | involved in activation of the prodrug, mechanism, overview. The reaction proceeds via the alpha-chloroamido derivative of the GSH-brostallicin adduct, is able to alkylate DNA in a sequence-specific manner and appears to be the active form of the drug, brostallicin cytotoxicity of brostallicin is higher in cells overexpressing either the GST-pi or the GST-mu gene | Homo sapiens | glutathionyl-brostallicin | - |
? | |
brostallicin + glutathione | isoenzymes GSTP1-1 and GSTM2-2 | Homo sapiens | glutathionyl-brostallicin | - |
? | |
glutathione + 1-chloro-2,4-dinitrobenzene | - |
Homo sapiens | S-(2,4-dinitrophenyl)glutathione + HCl | - |
? |
Synonyms | Comment | Organism |
---|---|---|
GST | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
25 | - |
assay at | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
6.5 | - |
assay at | Homo sapiens |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | inhibition kinetics and mechanism of brostallicin and derivatives, overview | Homo sapiens | |
0.028 | - |
glutathione | pH 6.5, 25°C, GSTM2-2 | Homo sapiens | |
0.037 | - |
1-chloro-2,4-dinitrobenzene | pH 6.5, 25°C, GSTM2-2 | Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.06 | - |
pH 6.5, 25°C, with isozyme GSTM2-2 | Homo sapiens | 4-(acryloylamino)-N-(5-[[5-([5-[(2-carbamimidamidoethyl)carbamoyl]-1-methyl-1H-pyrrol-3-yl]carbamoyl)-1-methyl-1H-pyrrol-3-yl]carbamoyl]-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide |
kcat/KM Value [1/mMs-1] | kcat/KM Value Maximum [1/mMs-1] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
4 | - |
brostallicin | pH 6.5, 25°C, isozyme GSTM2-2 | Homo sapiens | |
11 | - |
brostallicin | pH 6.5, 25°C, isozyme GSTP1-1 | Homo sapiens |