Application | Comment | Organism |
---|---|---|
drug development | testosterone is converted to 5alpha-dihydrotestosterone, which is present at high concentrations in patients with castration resistant prostate cancer (CRPC). Inhibition of 17beta-HSD5 is therefore considered to be a promising therapy for treating CRPC. High-throughput inhibitor screening, overview | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
recombinant expression of C-terminally His6-tagged enzyme in Escherichia coli strain BL21(DE3) | Homo sapiens |
Crystallization (Comment) | Organism |
---|---|
purified recombinant enzyme in ternary complex with NADP+ and one inhibitor, from inhibitors 1-6, 15 mg/ml protein in 10 mM potassium phosphate pH 7.4, 500 mM NaCl, 1 mM ethylenediaminetetraacetic acid, 1 mM dithiothreitol is mixed with crystallization solution containing 0.1 M sodium citrate, pH 5.5, 0.4 M ammonium acetate, 2.5% v/v 2-methyl-2,4-pentanediol, 22-30% w/v PEG 4000 for inhibitors 1-4, and containing 0.1 M HEPES pH 6.5, 0.2 M ammonium dihydrogen phosphate, 20-25% w/v PEG 3350 for inhibitors 5 and 6, X-ray diffraction structure determination analysis at 1.55-2.81 A resolution, modelling | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(3,6-dihydropyridin-1(2H)-yl)(1H-indol-2-yl)methanone | crystal structure analysis of enzyme-inhibitor complex | Homo sapiens | |
(5-methyl-1H-indol-2-yl)(4-propylpiperidin-1-yl)methanone | crystal structure analysis of enzyme-inhibitor complex | Homo sapiens | |
3-pentyl-2-[[(pyridin-2-yl)methyl]sulfanyl]-7-(pyrrolidine-1-carbonyl)quinazolin-4(3H)-one | crystal structure analysis of enzyme-inhibitor complex | Homo sapiens | |
4-chloro-N-[(4-chlorophenyl)methyl]-5-nitro-1H-pyrazole-3-carboxamide | crystal structure analysis of enzyme-inhibitor complex | Homo sapiens | |
4-nitro-2-([4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]methyl)phenol | crystal structure analysis of enzyme-inhibitor complex | Homo sapiens | |
5-(benzenesulfonyl)-2-nitrophenol | crystal structure analysis of enzyme-inhibitor complex | Homo sapiens | |
additional information | crystal structures of complexes of 17beta-HSD5 with structurally diverse inhibitors derived from high-throughput inhibitor screening, overview. Analysis of interactions between 17beta-HSD5 and inhibitors at the atomic level which enable structure-based drug design for anti-CRPC therapy | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
testosterone + NADP+ | Homo sapiens | - |
androstenedione + NADPH + H+ | - |
r |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P42330 | - |
- |
Purification (Comment) | Organism |
---|---|
recombinant C-terminally His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity and anion exchange chromatography, gel fitration, and ultrafiltration | Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
prostate | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
testosterone + NADP+ | - |
Homo sapiens | androstenedione + NADPH + H+ | - |
r |
Synonyms | Comment | Organism |
---|---|---|
17beta-HSD5 | - |
Homo sapiens |
AKR1C3 | - |
Homo sapiens |
type 5 17beta-hydroxysteroid dehydrogenase | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
22 | - |
assay at | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
6 | - |
assay at | Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NADP+ | - |
Homo sapiens | |
NADPH | - |
Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.000037 | - |
pH 6.0, 22°C | Homo sapiens | (5-methyl-1H-indol-2-yl)(4-propylpiperidin-1-yl)methanone | |
0.00029 | - |
pH 6.0, 22°C | Homo sapiens | 5-(benzenesulfonyl)-2-nitrophenol | |
0.00049 | - |
pH 6.0, 22°C | Homo sapiens | 4-nitro-2-([4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]methyl)phenol | |
0.0026 | - |
pH 6.0, 22°C | Homo sapiens | 4-chloro-N-[(4-chlorophenyl)methyl]-5-nitro-1H-pyrazole-3-carboxamide | |
0.0028 | - |
pH 6.0, 22°C | Homo sapiens | (3,6-dihydropyridin-1(2H)-yl)(1H-indol-2-yl)methanone | |
0.0029 | - |
pH 6.0, 22°C | Homo sapiens | 3-pentyl-2-[[(pyridin-2-yl)methyl]sulfanyl]-7-(pyrrolidine-1-carbonyl)quinazolin-4(3H)-one |
General Information | Comment | Organism |
---|---|---|
evolution | the enzyme belongs to the AKR1C subfamily, the members of which catalyze the reduction of ketosteroids and ketoprostaglandins | Homo sapiens |