Cloned (Comment) | Organism |
---|---|
the cDNA that encodes the mutant 3beta-HSD1 enzymes S194G-1 and R195P-1 are generated via double-stranded, PCR-based mutagenesis and inserted into baculovirus. The recombinant baculovirus system successfully expresses the mutant S194G-1 and R195P-1 enzyme proteins in Sf9 cells with the wild-type 3beta-HSD1 as the control | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
R195P | 2,16-dicyano-4,5-epoxy-androstane-3,17-dione competitively inhibits S194G-1 | Homo sapiens |
S194G | trilostane inhibits chimeric S194G-1 mutant (Ki: 0.00067 mM) with a noncompetitive mode compared to its 6.7fold higher affinity, competitive inhibition of 3beta-HSD1. 2,16-Dicyano-4,5-epoxy-androstane-3,17-dione inhibits S194G-1 with a 6.3fold higher Ki (0.0295 mM) than measured for 3beta-HSD1 (Ki: 0.0047 mM) but with the same competitive mode for both enzyme species | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
16-cyano-17-keto-trilostane | selective inhibitor | Homo sapiens | |
2,16-dicyano-4,5-epoxy-androstane-3,17-dione | competitively inhibits 3beta-HSD1 | Homo sapiens | |
trilostane | - |
Homo sapiens |
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 195P-1 mutant | Homo sapiens | |
0.0124 | - |
dehydroepiandrosterone | pH 7.4, 27°C, chimeric S194G-1 mutant | Homo sapiens | |
0.0205 | - |
NAD+ | pH 7.4, 27°C, chimeric 195P-1 mutant | Homo sapiens | |
0.0244 | - |
NAD+ | pH 7.4, 27°C, chimeric S194G-1 mutant | Homo sapiens | |
0.0341 | - |
NAD+ | pH 7.4, 27°C, wild-type enzyme | Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P14060 | - |
- |
Purification (Comment) | Organism |
---|---|
- |
Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
breast cancer cell | 3beta-HSD1 is selectively expressed in human placenta, mammary glands and breast tumors in women | Homo sapiens | - |
mammary gland | 3beta-HSD1 is selectively expressed in human placenta, mammary glands and breast tumors in women | Homo sapiens | - |
placenta | 3beta-HSD1 is selectively expressed in human placenta, mammary glands and breast tumors in women | Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
dehydroepiandrosterone + NAD+ | - |
Homo sapiens | androstenedione + NADH + H+ | - |
? |
Synonyms | Comment | Organism |
---|---|---|
3beta-HSD1 | - |
Homo sapiens |
3beta-hydroxysteroid dehydrogenase type 1 | - |
Homo sapiens |
Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.04 | - |
NAD+ | pH 7.4, 27°C, chimeric S194G-1 mutant | Homo sapiens | |
0.055 | - |
dehydroepiandrosterone | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
0.058 | - |
NAD+ | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
0.1 | - |
NAD+ | pH 7.4, 27°C, chimeric 195P-1 mutant | Homo sapiens | |
0.1283 | - |
dehydroepiandrosterone | pH 7.4, 27°C, chimeric 195P-1 mutant | Homo sapiens | |
0.13 | - |
dehydroepiandrosterone | pH 7.4, 27°C, chimeric S194G-1 mutant | Homo sapiens |
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 | Homo sapiens | |
0.00256 | - |
trilostane | pH 7.4, 27°C, chimeric 195P-1 mutant | Homo sapiens | |
0.0047 | - |
2,16-dicyano-4,5-epoxy-androstane-3,17-dione | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
0.0295 | - |
2,16-dicyano-4,5-epoxy-androstane-3,17-dione | pH 7.4, 27°C, chimeric S194G-1 mutant | Homo sapiens | |
0.0415 | - |
2,16-dicyano-4,5-epoxy-androstane-3,17-dione | pH 7.4, 27°C, chimeric 195P-1 mutant | Homo sapiens |
General Information | Comment | Organism |
---|---|---|
drug target | selective inhibition of 3beta-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 Value [1/mMs-1] | kcat/KM Value Maximum [1/mMs-1] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
1.64 | - |
NAD+ | pH 7.4, 27°C, chimeric S194G-1 mutant | Homo sapiens | |
1.7 | - |
NAD+ | pH 7.4, 27°C, wild-type enzyme | Homo sapiens | |
4.88 | - |
NAD+ | pH 7.4, 27°C, chimeric 195P-1 mutant | Homo sapiens | |
10.48 | - |
dehydroepiandrosterone | pH 7.4, 27°C, chimeric S194G-1 mutant | Homo sapiens | |
11.99 | - |
dehydroepiandrosterone | pH 7.4, 27°C, chimeric 195P-1 mutant | Homo sapiens | |
14.86 | - |
dehydroepiandrosterone | pH 7.4, 27°C, wild-type enzyme | Homo sapiens |