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Literature summary for 1.1.1.270 extracted from

  • Pham, J.H.; Will, C.M.; Mack, V.L.; Halbert, M.; Conner, E.A.; Bucholtz, K.M.; Thomas, J.L.
    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 .
    View publication on PubMed
Search for more literature for 1.1.1.270

Cloned(Commentary)

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

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

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 [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

Organism UniProt Comment Textmining
Homo sapiens P14060
-
-

Purification (Commentary)

Purification (Comment) Organism
-
 Homo sapiens

Source Tissue

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 and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
dehydroepiandrosterone + NAD+
-
 Homo sapiens androstenedione + NADH + H+
-
 ?

Synonyms

Synonyms Comment Organism
3beta-HSD1
-
 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 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 [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

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 [mM/s]

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