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Literature summary for 1.1.1.145 extracted from
- Structure-function relationships for the selective inhibition of human 3beta-hydroxysteroid dehydrogenase type 1 by a novel androgen analog (2017), J. Steroid Biochem. Mol. Biol., 174, 257-264 .
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| expression of the chimeric S194G-1 mutant of the enzyme (3beta-HSD1) | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| R195P | 16-cyano-17-keto-trilostane inhibits the chimeric R195P-1 mutant of the enzyme (3beta-HSD1) with a noncompetitive mode compared to competitive inhibition of the wild-type enzyme (3beta-HSD1) | Homo sapiens |
| S194G | 16-cyano-17-keto-trilostane and trilostane inhibits the chimeric S194G-1 mutant of the enzyme (3beta-HSD1) with a noncompetitive mode compared to competitive inhibition of the wild-type enzyme (3beta-HSD1) | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| 16-cyano-17-keto-trilostane | i.e 2,16-dicyano-4,5-epoxy-androstane-3,17-dione. Competitive, selective inhibitor of wild-type enzyme and chimeric S194G-1 mutant of the enzyme (3beta-HSD1). Noncompetitive inhibitor of chimeric R195P-1 mutant of the enzyme. Selective inhibition of 3beta-HSD1 may prevent spontaneous premature birth; i.e 2,16-dicyano-4,5-epoxy-androstane-3,17-dione. noncompetitive inhibitor; selective inhibitor | Homo sapiens | |
| 2,16-dicyano-4,5-epoxy-androstane-3,17-dione | competitively inhibits 3beta-HSD1 | Homo sapiens | |
| trilostane | noncompetitive inhibitor; noncompetitive inhibitor of chimeric S194G-1 mutant and chimeric R195P-1 mutant of the enzyme (3beta-HSD1). Competitive inhibition of wild-type enzyme | Homo sapiens |  |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.0037 | - |
dehydroepiandrosterone | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
| 0.0107 | - |
dehydroepiandrosterone | pH 7.4, 27°C, chimeric R195P-1 mutant of the enzyme (3beta-HSD1) | Homo sapiens | |
| 0.0124 | - |
dehydroepiandrosterone | pH 7.4, 27°C, chimeric S194G-1 mutant of the enzyme (3beta-HSD1) | Homo sapiens | |
| 0.0156 | - |
dehydroepiandrosterone | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
| 0.0205 | - |
NAD+ | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
| 0.0244 | - |
NAD+ | pH 7.4, 27°C, chimeric R195P-1 mutant of the enzyme (3beta-HSD1) | Homo sapiens | |
| 0.0341 | - |
NAD+ | pH 7.4, 27°C, chimeric S194G-1 mutant of the enzyme (3beta-HSD1) | Homo sapiens | |
| 0.0863 | - |
NAD+ | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | P14060 | - |
- |
| Homo sapiens | P26439 | - |
- |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| purification of the chimeric S194G-1 mutant of the enzyme (3beta-HSD1) | Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| adrenal gland | 3beta-HSD21 is selectively expressed in adrenal glands and ovaries | Homo sapiens | - |
| adrenal gland | selectively expressed in adrenal glands and ovaries | Homo sapiens | - |
| breast cancer cell | - |
Homo sapiens | - |
| mammary gland | - |
Homo sapiens | - |
| ovary | - |
Homo sapiens | - |
| ovary | 3beta-HSD21 is selectively expressed in adrenal glands and ovaries | Homo sapiens | - |
| placenta | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| dehydroepiandrosterone + NAD+ | - |
Homo sapiens | 5-androstene-3,17-dione + NADH + H+ | - |
? | |
| dehydroepiandrosterone + NAD+ | - |
Homo sapiens | androstenedione + NADH + H+ | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| 3beta-HSD1 | - |
Homo sapiens |
| 3beta-HSD2 | - |
Homo sapiens |
| 3beta-hydroxysteroid dehydrogenase type 1 | - |
Homo sapiens |
Turnover Number [1/s]
| Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.04 | - |
NAD+ | pH 7.4, 27°C, chimeric R195P-1 mutant of the enzyme (3beta-HSD1) | Homo sapiens | |
| 0.055 | - |
dehydroepiandrosterone | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
| 0.06 | - |
NAD+ | pH 7.4, 27°C, chimeric S194G-1 mutant of the enzyme (3beta-HSD1) | Homo sapiens | |
| 0.1 | - |
NAD+ | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
| 0.118 | - |
NAD+ | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
| 0.12 | - |
NAD+ | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
| 0.128 | - |
dehydroepiandrosterone | pH 7.4, 27°C, chimeric R195P-1 mutant of the enzyme (3beta-HSD1) | Homo sapiens | |
| 0.13 | - |
dehydroepiandrosterone | pH 7.4, 27°C, chimeric S194G-1 mutant of the enzyme (3beta-HSD1) | Homo sapiens | |
| 0.145 | - |
dehydroepiandrosterone | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| NAD+ | - |
Homo sapiens | |
Ki Value [mM]
| Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.0001 | - |
trilostane | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
| 0.00067 | - |
trilostane | pH 7.4, 27°C, chimeric S194G-1 mutant of the enzyme (3beta-HSD1) | Homo sapiens | |
| 0.0016 | - |
trilostane | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
| 0.0016 | - |
16-cyano-17-keto-trilostane | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
| 0.00256 | - |
trilostane | pH 7.4, 27°C, chimeric R195P-1 mutant of the enzyme (3beta-HSD1) | Homo sapiens | |
| 0.0047 | - |
16-cyano-17-keto-trilostane | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
| 0.0295 | - |
16-cyano-17-keto-trilostane | pH 7.4, 27°C, chimeric S194G-1 mutant of the enzyme (3beta-HSD1) | Homo sapiens | |
| 0.0307 | - |
trilostane | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
| 0.0307 | - |
2,16-dicyano-4,5-epoxy-androstane-3,17-dione | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
| 0.0413 | - |
16-cyano-17-keto-trilostane | pH 7.4, 27°C, chimeric R195P-1 mutant of the enzyme (3beta-HSD1) | Homo sapiens |
General Information
| General Information | Comment | Organism |
|---|---|---|
| drug target | 16-cyano-17-keto-trilostane is a selective inhibitor of 3beta-hydroxysteroid dehydrogenase type 1. Selective inhibition of beta-HSD1 may prevent spontaneous premature birth. Inhibition of 3beta-HSD1 decreases placental estradiol production that promotes labor. The 3beta-HSD1 inhibitor may be administered with 17alpha-hydroxyprogesterone caproate | Homo sapiens |
kcat/KM [mM/s]
| kcat/KM Value [1/mMs-1] | kcat/KM Value Maximum [1/mMs-1] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.176 | - |
NAD+ | pH 7.4, 27°C, chimeric S194G-1 mutant of the enzyme (3beta-HSD1) | Homo sapiens | |
| 0.93 | - |
dehydroepiandrosterone | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
| 1.37 | - |
NAD+ | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
| 1.4 | - |
NAD+ | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
| 1.64 | - |
NAD+ | pH 7.4, 27°C, chimeric R195P-1 mutant of the enzyme (3beta-HSD1) | Homo sapiens | |
| 4.8 | - |
NAD+ | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
| 9.29 | - |
dehydroepiandrosterone | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
| 10.48 | - |
dehydroepiandrosterone | pH 7.4, 27°C, chimeric S194G-1 mutant of the enzyme (3beta-HSD1) | Homo sapiens | |
| 11.96 | - |
dehydroepiandrosterone | pH 7.4, 27°C, chimeric R195P-1 mutant of the enzyme (3beta-HSD1) | Homo sapiens | |
| 14.86 | - |
dehydroepiandrosterone | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
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