Cloned (Comment) | Organism |
---|---|
recombinant expression of enzyme in Escherichia coli strain BL21(DE3) | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
C159S | site-directed mutagenesis, the mutant shows altered susceptibillity to 2-aminothiazole inhibitors compared to the wild-type enzyme | Homo sapiens |
C300S | site-directed mutagenesis, the mutant shows altered susceptibillity to 2-aminothiazole inhibitors compared to the wild-type enzyme | Homo sapiens |
C416S | site-directed mutagenesis, the mutant shows altered susceptibillity to 2-aminothiazole inhibitors compared to the wild-type enzyme | Homo sapiens |
C418S | site-directed mutagenesis, the mutant shows altered susceptibillity to 2-aminothiazole inhibitors compared to the wild-type enzyme | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
4-(4-(4-chlorophenyl)thiazol-2-ylimino)cyclohexa-2,5-dienone | ST-1905 | Homo sapiens | |
4-[(4-cyclohexyl-5-methyl-1,3-thiazol-2-yl)amino]-2,6-dimethylphenol | lead compound, in vitro pharmacokinetic profile, shows no cytotoxicity, overview | Homo sapiens | |
4-[[4-(2,4-dichlorophenyl)-5-methyl-1,3-thiazol-2-yl]amino]-2,6-dimethylphenol | lead compound, in vitro pharmacokinetic profile, shows no cytotoxicity, overview | Homo sapiens | |
4-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino]phenol | - |
Homo sapiens | |
4-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]imino]cyclohexa-2,5-dien-1-one | - |
Homo sapiens | |
BWA-4C | - |
Homo sapiens | |
additional information | molecular mechanism of 5-lipoxygenase inhibition by 2-aminothiazoles, overview. ST-1083 and ST-1905, but not the lead compounds, show covalent binding to 5-LO and the potency of ST-1083 and ST-1905, but not of the lead compounds is impaired for 5-LO cysteine mutants. Especially the cysteines 159, 300, 416, and 418, located in the substrate entry channel of 5-LO, are prone to be potential targets for inhibition. The lead compounds show no dependency on thiol level | Homo sapiens | |
U73122 | - |
Homo sapiens |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Fe2+ | required, iron reduction from Fe3+ to Fe2+ during catalyis | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
arachidonate + O2 | Homo sapiens | - |
(5S,6S,7E,9E,11Z,14Z)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P09917 | - |
- |
Purification (Comment) | Organism |
---|---|
recombinant enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, and anion exchange chromatography | Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
Hep-G2 cell | - |
Homo sapiens | - |
leukocyte | polymorphonuclear | Homo sapiens | - |
U-937 cell | leukemic monocyte cells | Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
arachidonate + O2 | - |
Homo sapiens | (5S,6S,7E,9E,11Z,14Z)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O | - |
? |
Synonyms | Comment | Organism |
---|---|---|
5-lipoxygenase | - |
Homo sapiens |
5-LO | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.4 | - |
assay at | Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.00003 | - |
pH 7.4, 37°C, recombinant enzyme | Homo sapiens | 4-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino]phenol | |
0.00004 | - |
pH 7.4, 37°C, recombinant enzyme | Homo sapiens | 4-(4-(4-chlorophenyl)thiazol-2-ylimino)cyclohexa-2,5-dienone |
General Information | Comment | Organism |
---|---|---|
physiological function | 5-lipoxygenase is implicated in the pathogenesis of inflammatory and immune diseases | Homo sapiens |