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Literature summary for 1.1.1.270 extracted from

  • Thomas, J.L.; Mack, V.L.; Sun, J.; Terrell, J.R.; Bucholtz, K.M.
    The functions of key residues in the inhibitor, substrate and cofactor sites of human 3beta-hydroxysteroid dehydrogenase type 1 are validated by mutagenesis (2010), J. Steroid Biochem. Mol. Biol., 120, 192-199.
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
medicine the selective inhibition of human 3beta-HSD1 in breast tumors represents a potential treatment for hormone-sensitive breast cancer Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
expression of wild-type and mutant enzymes in Spodoptera frugiperda Sf9 cells using the baculovirus transfection system Homo sapiens

Protein Variants

Protein Variants Comment Organism
D61N site-directed mutagenesis, mutation in isozyme 3beta-HSD1 Homo sapiens
D61V site-directed mutagenesis, mutation in isozyme 3beta-HSD1 Homo sapiens
E192A site-directed mutagenesis, mutation in isozyme 3beta-HSD1 Homo sapiens
P195R site-directed mutagenesis, mutation in isozyme 3beta-HSD2 Homo sapiens
R195P site-directed mutagenesis, mutation in isozyme 3beta-HSD1 Homo sapiens
T8A site-directed mutagenesis, mutation in isozyme 3beta-HSD1 Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
trilostane competitive for 3beta-HSD1, noncompetitive for 3beta-HSD2 Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant wild-type and mutant enzymes from Sf9 insect cells by ultracentrifugation Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
breast cancer cell selective expression of 3beta-HSD1 Homo sapiens
-
mammary gland selective expression of 3beta-HSD1 Homo sapiens
-
additional information isozymes 3beta-HSD1 and 3beta-HSD2 are encoded by two distinct genes which are expressed in a tissue-specific pattern Homo sapiens
-
placenta selective expression of 3beta-HSD1 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
16alpha-hydroxy-dehydroepiandrosterone + NADH + H+
-
Homo sapiens ?
-
?
16beta-hydroxy-dehydroepiandrosterone + NADH + H+
-
Homo sapiens ?
-
?
17alpha-hydroxypregnenolone + NADH + H+
-
Homo sapiens 17alpha-hydroxyprogesterone + NAD+
-
?
5-androstene-3,17-dione + NAD+
-
Homo sapiens dehydroepiandrosterone + NADH + H+
-
?
dehydroepiandrosterone + NADH + H+
-
Homo sapiens 5-androstene-3,17-dione + NAD+
-
?
additional information both isoforms of the enzyme catalyze the conversion of 3beta-hydroxy-5-ene-steroids (dehydroepiandrosterone, 17alpha-hydroxypregnenolone, pregnenolone) to 3-oxo-4-ene-steroids (androstenedione, 17alpha-hydroxyprogestrone, progesterone) on a single, dimeric protein containing both enzyme activities Homo sapiens ?
-
?
pregnenolone + NADH + H+
-
Homo sapiens progesterone + NAD+
-
?

Synonyms

Synonyms Comment Organism
3beta-HSD1
-
Homo sapiens
3beta-HSD2
-
Homo sapiens
3beta-hydroxysteroid dehydrogenase type 1
-
Homo sapiens
3beta-hydroxysteroid dehydrogenase/Delta 5->4-isomerase type 1
-
Homo sapiens
3beta-hydroxysteroid dehydrogenase/Delta 5->4-isomerase type 2
-
Homo sapiens
SDR11E1
-
Homo sapiens
SDR11E2
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
27
-
assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
assay at Homo sapiens

Cofactor

Cofactor Comment Organism Structure
NAD+
-
Homo sapiens
NADH
-
Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.0001
-
trilostane 3beta-HSD1 wild-type, pH 7.4, 27°C Homo sapiens
0.00019
-
trilostane 3beta-HSD2 mutant P195R, pH 7.4, 27°C Homo sapiens
0.0016
-
trilostane 3beta-HSD2 wild-type, pH 7.4, 27°C Homo sapiens
0.00256
-
trilostane 3beta-HSD1 mutant R195P, pH 7.4, 27°C Homo sapiens

General Information

General Information Comment Organism
evolution human 3beta-hydroxysteroid dehydrogenase is a member of the short-chain dehydrogenase/reductase (SDR) family of enzymes, all of which contain the Rossmann-fold domain with a beta-alpha-beta-alpha-beta-alpha-beta-alpha-beta folding pattern that binds cofactor and substrate Homo sapiens
metabolism the enzyme catalyzes the first step in the conversion of dehydroepiandrosterone to estradiol Homo sapiens
physiological function the enzyme promotes tumor growth in placenta, mammary glands, and breasts. In human adrenals, 3beta-HSD2 is required for the production of cortisol and aldosterone Homo sapiens