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Literature summary for 1.1.1.145 extracted from

  • Thomas, J.; Bucholtz, K.; Kacsoh, B.
    Selective inhibition of human 3beta-hydroxysteroid dehydrogenase type 1 as a potential treatment for breast cancer (2011), J. Steroid Biochem. Mol. Biol., 125, 57-65.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
-
Homo sapiens

Protein Variants

Protein Variants Comment Organism
H156Y 5fold decrease in catalytic efficiency Homo sapiens
Q105M1 5fold decrease in catalytic efficiency Homo sapiens
Q105M1 mutant retains the lower affinity profile of inhibition by epostane that is observed with wild-type 3beta-HSD2 Homo sapiens
R195P mutation of isoform 3betaHSD1 to corresponding residue in isoform 3betaHSD2. Mutation shifts the dehydroepiandrosterone substrate kinetics to the lower affinity profile of isoform 3beta-HSD2 Homo sapiens
R195P mutation of isoform 3betaHSD2 to corresponding residue in isoform 3betaHSD1. Mutation shifts the dehydroepiandrosterone substrate kinetics to the higher affinity profile of isoform 3beta-HSD1 Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
epostane inhibits the dehydroepiandrosterone-induced proliferation of MCF-7 cells expressing isoform 3beta-HSD1 with 12- to 16fold lower IC50 values compared to the MCF-7 cells expressing isoform 3beta-HSD2. Epostane also competitively inhibits purified human 3beta-HSD1 with 12fold to 16fold lower Ki values compared to the noncompetitive Ki values measured for human 3beta-HSD2; inhibits the dehydroepiandrosterone-induced proliferation of MCF-7 cells expressing isoform 3beta-HSD1 with 12- to 16fold lower IC50 values compared to the MCF-7 cells expressing isoform 3beta-HSD. Epostane also competitively inhibits purified human 3beta-HSD1 with 12fold to 16fold lower Ki values compared to the noncompetitive Ki values measured for human 3beta-HSD2 Homo sapiens
trilostane inhibits the dehydroepiandrosterone-induced proliferation of MCF-7 cells expressing isoform 3beta-HSD1 with 12- to 16fold lower IC50 values compared to the MCF-7 cells expressing isoform 3beta-HSD2. Trilostane also competitively inhibits purified human 3beta-HSD1 with 12fold to 16fold lower Ki values compared to the noncompetitive Ki values measured for human 3beta-HSD2; inhibits the dehydroepiandrosterone-induced proliferation of MCF-7 cells expressing isoform 3beta-HSD1 with 12- to 16fold lower IC50 values compared to the MCF-7 cells expressing isoform 3beta-HSD2. Trilostane also competitively inhibits purified human 3beta-HSD1 with 12fold to 16fold lower Ki values compared to the noncompetitive Ki values measured for human 3beta-HSD2. Trilostane is docked in the active site of isoform 3beta-HSD1, and residue Arg195 in 3beta-HSD1 is a potentially critical residue Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.00164
-
dehydroepiandrosterone mutant Q105M, pH 7.4, 27°C Homo sapiens
0.0037
-
dehydroepiandrosterone wild-type, pH 7.4, 27°C Homo sapiens
0.0077
-
dehydroepiandrosterone mutant P195R, pH 7.4, 27°C Homo sapiens
0.0107
-
dehydroepiandrosterone mutant R195P, pH 7.4, 27°C Homo sapiens
0.0156
-
dehydroepiandrosterone wild-type, pH 7.4, 27°C Homo sapiens
0.04
-
dehydroepiandrosterone mutant Q105M, pH 7.4, 27°C Homo sapiens
0.0424
-
dehydroepiandrosterone mutant H156Y, pH 7.4, 27°C Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens P14060 isoform 3betaHSD1
-
Homo sapiens P26439 isoform 3betaHSD2
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
dehydroepiandrosterone + NAD+
-
Homo sapiens androst-5-en-3,17-dione + NADH + H+
-
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Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.055
-
dehydroepiandrosterone wild-type, pH 7.4, 27°C Homo sapiens
0.075
-
dehydroepiandrosterone mutant Q105M, pH 7.4, 27°C Homo sapiens
0.093
-
dehydroepiandrosterone mutant P195R, pH 7.4, 27°C Homo sapiens
0.113
-
dehydroepiandrosterone mutant Q105M, pH 7.4, 27°C Homo sapiens
0.118
-
dehydroepiandrosterone mutant H156Y, pH 7.4, 27°C Homo sapiens
0.13
-
dehydroepiandrosterone mutant R195P, pH 7.4, 27°C Homo sapiens
0.145
-
dehydroepiandrosterone wild-type, pH 7.4, 27°C Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.00007
-
epostane wild-type, pH 7.4, 27°C Homo sapiens
0.0001
-
trilostane wild-type, pH 7.4, 27°C Homo sapiens
0.00098
-
epostane wild-type, pH 7.4, 27°C Homo sapiens
0.00118
-
epostane mutant H156Y, pH 7.4, 27°C Homo sapiens
0.00164
-
epostane mutant Q105M, pH 7.4, 27°C Homo sapiens
0.00184
-
epostane mutant Q105M, pH 7.4, 27°C Homo sapiens
0.0019
-
trilostane mutant P195R, pH 7.4, 27°C Homo sapiens
0.00256
-
trilostane mutant R195P, pH 7.4, 27°C Homo sapiens
0.016
-
trilostane wild-type, pH 7.4, 27°C Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
0.0028
-
dehydroepiandrosterone mutant H156Y, pH 7.4, 27°C Homo sapiens
0.0028
-
dehydroepiandrosterone mutant Q105M, pH 7.4, 27°C Homo sapiens
0.003
-
dehydroepiandrosterone mutant Q105M, pH 7.4, 27°C Homo sapiens
0.0073
-
dehydroepiandrosterone wild-type, pH 7.4, 27°C Homo sapiens
0.012
-
dehydroepiandrosterone mutant P195R, pH 7.4, 27°C Homo sapiens
0.012
-
dehydroepiandrosterone mutant R195P, pH 7.4, 27°C Homo sapiens
0.015
-
dehydroepiandrosterone wild-type, pH 7.4, 27°C Homo sapiens