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Literature summary for 2.5.1.18 extracted from

  • Pezzola, S.; Antonini, G.; Geroni, C.; Beria, I.; Colombo, M.; Broggini, M.; Mongelli, N.; Leboffe, L.; MacArthur, R.; Mozzi, A.F.; Federici, G.; Caccuri, A.M.
    Role of glutathione transferases in the mechanism of brostallicin activation (2010), Biochemistry, 49, 226-235.
    View publication on PubMed
Search for more literature for 2.5.1.18

Cloned(Commentary)

Cloned (Comment) Organism
isozymes GSTP1-1 and GSTM2-2, expression in Escherichia coli Homo sapiens

Inhibitors

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 [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/ Products (Substrates)

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

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant isozymes GSTP1-1 and GSTM2-2 from Escherichia coli Homo sapiens

Source Tissue

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 and Products (Substrate)

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

Synonyms Comment Organism
GST
-
 Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
 assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
6.5
-
 assay at Homo sapiens

Ki Value [mM]

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 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 [mM/s]

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