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Literature summary for 1.1.1.357 extracted from
- Methoxychlor and its metabolite HPTE inhibit rat neurosteroidogenic 3alpha-hydroxysteroid dehydrogenase and retinol dehydrogenase 2 (2018), Neurosci. Lett., 684, 169-174 .
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| gene Akr1c14, recombinant expression in COS-1 cells | Rattus norvegicus |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| 2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane | hydroxychlor (HPTE), competitive without cofactor but mixed-type inhibition with cofactor, methoxychlor and its metabolite HPTE inhibit rat neurosteroidogenic 3alpha-hydroxysteroid dehydrogenase | Rattus norvegicus | |
| methoxychlor | MXC, methoxychlor and its metabolite hydroxychlor (HPTE) inhibit rat neurosteroidogenic 3alpha-hydroxysteroid dehydrogenase. Methoxychlor is primarily used as an insecticide, and it is widely present in the environment | Rattus norvegicus |  |
| additional information | binding mode determination of methoxychlor (MXC) and HPTE from the crystal structure of AKR1C14 by molecular docking. HPTE has a higher affinity with the enzyme than methoxychlor. HPTE is more potent than methoxychlor to inhibit both AKR1C14 and retinol dehydrogenase 2 (RDH2, EC 1.1.1.53). Both MXC and HPTE interact with Y55, K84, H117, W227, and Y310 of the enzyme. HPTE also forms hydrogen bond with V25 residue of AKR1C14. Both MXC and HPTE inhibit rat AKR1C14 in a competitive mode against DHT. No inhibition by DMSO | Rattus norvegicus |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.00311 | - |
dihydrotestosterone | pH 7.2, 37°C, recombinant enzyme | Rattus norvegicus | |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cytosol | - |
Rattus norvegicus | 5829 | - |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| dihydroprogesterone + NADPH + H+ | Rattus norvegicus | - |
allopregnanolone + NADP+ | - |
? | |
| dihydrotestosterone + NADPH + H+ | Rattus norvegicus | - |
5alpha-androstane-3alpha,17beta-diol + NADP+ | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Rattus norvegicus | - |
- |
- |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant enzyme from cytosol of COS-1 cells by ultracentrifugation | Rattus norvegicus |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| brain | - |
Rattus norvegicus | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| dihydroprogesterone + NADPH + H+ | - |
Rattus norvegicus | allopregnanolone + NADP+ | - |
? | |
| dihydrotestosterone + NADPH + H+ | - |
Rattus norvegicus | 5alpha-androstane-3alpha,17beta-diol + NADP+ | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| 3alpha-hydroxysteroid dehydrogenase | - |
Rattus norvegicus |
| AKR1C14 | - |
Rattus norvegicus |
| type I 3alpha-HSD | - |
Rattus norvegicus |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 37 | - |
assay at | Rattus norvegicus |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7.2 | - |
assay at | Rattus norvegicus |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| NADPH | - |
Rattus norvegicus | |
Ki Value [mM]
| Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | inhibition kinetics | Rattus norvegicus |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.0026 | - |
pH 7.2, 37°C, recombinant enzyme | Rattus norvegicus | 2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane | |
| 0.1 | - |
above, pH 7.2, 37°C, recombinant enzyme | Rattus norvegicus | methoxychlor | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | enzyme AKR1C14 belongs to the aldo-keto reductase family | Rattus norvegicus |
| metabolism | the homeostasis of neurosteroids, such as allopregnanolone and 5alpha-androstane-3alpha,17beta-diol (DIOL), depends on the catalysis of AKR1C14 and RDH2. These two enzymes are present in the different subcellular regions, with AKR1C14 in the cytoplasm and RDH2 in the smooth endoplasmic reticulum (microsome), and they use different cofactors, with AKR1C14 of NADPH and RDH2 of NAD+, and the cofactor availability determines the catalytic direction | Rattus norvegicus |
| additional information | AKR1C14 has two substrate binding sites, the steroid binding and the cofactor binding site | Rattus norvegicus |
| physiological function | enzyme AKR1C14 adds a hydrogen to the 3alpha-position of many steroids, including neurosteroids. It is a cytosolic NADPH-dependent enzyme, which primarily catalyzes the formation of allopregnanolone or 5alpha-androstane-3alpha,17beta-diol (DIOL) from dihydroprogesterone and dihydrotestosterone (DHT), respectively | Rattus norvegicus |
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Release 2023.1 (January 2023)
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