Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary 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

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

Cloned(Commentary)

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

Protein Variants

EC Number Protein Variants Comment Organism
1.1.1.145 D61N D61N mutation produces a 1.3fold increase in Km for the dehydroepiandrosterone substrate, a 1.9fold increase in Km for NAD+ utilization by the 3beta-HSD activity and little change in isomerase kinetics for either substrate or cofactor Homo sapiens
1.1.1.145 D61V mutant shows no enzymatic activity Homo sapiens
1.1.1.145 E192A the E192A mutation causes an 8.2fold increase in Km (dehydroepiandrosterone) and no change in the Km for NAD+ Homo sapiens
1.1.1.145 R195P R195P mutation shifts the high-affinity, competitive inhibition profile of 3beta-HSD1 to a low-affinity (Ki= 2.56 microM), noncompetitive inhibition profile. R195P mutant has a 10.4fold higher Km value for 16beta-hydroxy-dehydroepiandrosterone compared to wild-type 3beta-HSD1. Km values for 16alpha-hydroxy-dehydroepiandrosterone and dehydroepiandrosterone are also inreased compared to wild-type (kcat values are decreased compared to wild-type) Homo sapiens
1.1.1.145 R195R the P195R mutation shifts the low-affinity, noncompetitive inhibition profile of 3beta-HSD2 to a high affinity (Ki= 0.19 microM), competitive inhibition profile. The P195R mutant has a 12.2fold lower Km value for 16beta-hydroxy-dehydroepiandrosterone compared to wild-type 3beta-HSD2. The coenzyme values measured for P195R mutant are similar to those measured for wildtype 3beta-HSD2 Homo sapiens
1.1.1.145 T8A mutant shows almost similar kinetic values as wild-type Homo sapiens
1.1.1.270 D61N site-directed mutagenesis, mutation in isozyme 3beta-HSD1 Homo sapiens
1.1.1.270 D61V site-directed mutagenesis, mutation in isozyme 3beta-HSD1 Homo sapiens
1.1.1.270 E192A site-directed mutagenesis, mutation in isozyme 3beta-HSD1 Homo sapiens
1.1.1.270 P195R site-directed mutagenesis, mutation in isozyme 3beta-HSD2 Homo sapiens
1.1.1.270 R195P site-directed mutagenesis, mutation in isozyme 3beta-HSD1 Homo sapiens
1.1.1.270 T8A site-directed mutagenesis, mutation in isozyme 3beta-HSD1 Homo sapiens

Inhibitors

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

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.1.1.145 0.0014
-
 16beta-hydroxy-dehydroepiandrosterone wild-type 3beta-HSD1, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0015
-
 16beta-hydroxy-dehydroepiandrosterone mutant R195R, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0025
-
 NADH mutant E192A, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0036
-
 NADH mutant R195P, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0037
-
 dehydroepiandrosterone wild-type 3beta-HSD1, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.004
-
 16alpha-hydroxy-dehydroepiandrosterone mutant R195R, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0046
-
 NADH wild-type 3beta-HSD1, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0055
-
 NADH mutant R195R, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0064
-
 16alpha-hydroxy-dehydroepiandrosterone wild-type 3beta-HSD1, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0065
-
 NADH mutant E192A, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0072
-
 NADH mutant D61N, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0077
-
 dehydroepiandrosterone mutant R195R, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0082
-
 dehydroepiandrosterone mutant E192A, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0107
-
 dehydroepiandrosterone mutant R195P, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0126
-
 NADH wild-type 3beta-HSD2, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0148
-
 16alpha-hydroxy-dehydroepiandrosterone wild-type 3beta-HSD2, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.015
-
 16beta-hydroxy-dehydroepiandrosterone mutant R195P, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0156
-
 dehydroepiandrosterone wild-type 3beta-HSD2, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0184
-
 16beta-hydroxy-dehydroepiandrosterone wild-type 3beta-HSD2, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0196
-
 16alpha-hydroxy-dehydroepiandrosterone mutant R195P, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0205
-
 NAD+ mutant R195P, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0333
-
 NAD+ mutant E192A, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0341
-
 NAD+ wild-type 3beta-HSD1, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0351
-
 NAD+ mutant E192A, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0351
-
 dehydroepiandrosterone mutant E192A, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0564
-
 NAD+ mutant R195R, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0643
-
 NAD+ mutant D61N, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0643
-
 dehydroepiandrosterone mutant D61N, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.0863
-
 NAD+ wild-type 3beta-HSD2, pH 7.4, 27°C Homo sapiens

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
1.1.1.145 42000
-
 SDS-PAGE Homo sapiens

Organism

EC Number Organism UniProt Comment Textmining
1.1.1.145 Homo sapiens P14060
-
-
1.1.1.145 Homo sapiens P26439
-
-
1.1.1.270 Homo sapiens
-
-
-

Purification (Commentary)

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

Source Tissue

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

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.1.1.145 16alpha-hydroxy-dehydroepiandrosterone + NAD+
-
 Homo sapiens ?
-
 ?
1.1.1.145 16alpha-hydroxy-dehydroepiandrosterone + NAD+
-
 Homo sapiens ? + NADH
-
 ?
1.1.1.145 16beta-hydroxy-dehydroepiandrosterone + NAD+
-
 Homo sapiens ?
-
 ?
1.1.1.145 16beta-hydroxy-dehydroepiandrosterone + NAD+
-
 Homo sapiens ? + NADH
-
 ?
1.1.1.145 androst-5-en-3,17-dione + NADH
-
 Homo sapiens dehydroepiandrosterone + NAD+
-
 r
1.1.1.145 dehydroepiandrosterone + NAD+
-
 Homo sapiens androst-5-en-3,17-dione + NADH + H+
-
 ?
1.1.1.145 dehydroepiandrosterone + NAD+
-
 Homo sapiens androst-5-en-3,17-dione + NADH + H+
-
 r
1.1.1.270 16alpha-hydroxy-dehydroepiandrosterone + NADH + H+
-
 Homo sapiens ?
-
 ?
1.1.1.270 16beta-hydroxy-dehydroepiandrosterone + NADH + H+
-
 Homo sapiens ?
-
 ?
1.1.1.270 17alpha-hydroxypregnenolone + NADH + H+
-
 Homo sapiens 17alpha-hydroxyprogesterone + NAD+
-
 ?
1.1.1.270 5-androstene-3,17-dione + NAD+
-
 Homo sapiens dehydroepiandrosterone + NADH + H+
-
 ?
1.1.1.270 dehydroepiandrosterone + NADH + H+
-
 Homo sapiens 5-androstene-3,17-dione + NAD+
-
 ?
1.1.1.270 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 ?
-
 ?
1.1.1.270 pregnenolone + NADH + H+
-
 Homo sapiens progesterone + NAD+
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.1.1.145 3beta-HSD1
-
 Homo sapiens
1.1.1.145 3beta-HSD2
-
 Homo sapiens
1.1.1.270 3beta-HSD1
-
 Homo sapiens
1.1.1.270 3beta-HSD2
-
 Homo sapiens
1.1.1.270 3beta-hydroxysteroid dehydrogenase type 1
-
 Homo sapiens
1.1.1.270 3beta-hydroxysteroid dehydrogenase/Delta 5->4-isomerase type 1
-
 Homo sapiens
1.1.1.270 3beta-hydroxysteroid dehydrogenase/Delta 5->4-isomerase type 2
-
 Homo sapiens
1.1.1.270 SDR11E1
-
 Homo sapiens
1.1.1.270 SDR11E2
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.1.1.145 27
-
 assay at Homo sapiens
1.1.1.270 27
-
 assay at Homo sapiens

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
1.1.1.145 0.02
-
 NAD+ mutant E192A, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.03
-
 dehydroepiandrosterone mutant E192A, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.04
-
 dehydroepiandrosterone mutant D61N, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.04
-
 NAD+ mutant E192A, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.04
-
 16beta-hydroxy-dehydroepiandrosterone wild-type 3beta-HSD1, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.05
-
 16beta-hydroxy-dehydroepiandrosterone mutant R195R, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.05
-
 NAD+ wild-type 3beta-HSD1, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.05
-
 dehydroepiandrosterone wild-type 3beta-HSD1, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.06
-
 NAD+ mutant D61N, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.06
-
 dehydroepiandrosterone mutant E192A, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.07
-
 16alpha-hydroxy-dehydroepiandrosterone mutant R195R, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.09
-
 dehydroepiandrosterone mutant R195R, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.09
-
 16alpha-hydroxy-dehydroepiandrosterone wild-type 3beta-HSD1, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.1
-
 NAD+ mutant R195P, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.11
-
 NAD+ wild-type 3beta-HSD2, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.12
-
 dehydroepiandrosterone mutant R195P, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.14
-
 dehydroepiandrosterone wild-type 3beta-HSD2, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.14
-
 16beta-hydroxy-dehydroepiandrosterone wild-type 3beta-HSD2, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.15
-
 16beta-hydroxy-dehydroepiandrosterone mutant R195P, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.15
-
 16alpha-hydroxy-dehydroepiandrosterone mutant R195P, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.15
-
 16alpha-hydroxy-dehydroepiandrosterone wild-type 3beta-HSD2, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.17
-
 NAD+ mutant R195R, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.31
-
 NADH mutant E192A, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.69
-
 NADH mutant E192A, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.75
-
 NADH wild-type 3beta-HSD1, pH 7.4, 27°C Homo sapiens
1.1.1.145 0.76
-
 NADH mutant D61N, pH 7.4, 27°C Homo sapiens
1.1.1.145 1.03
-
 NADH mutant R195P, pH 7.4, 27°C Homo sapiens
1.1.1.145 1.49
-
 NADH mutant R195R, pH 7.4, 27°C Homo sapiens
1.1.1.145 1.65
-
 NADH wild-type 3beta-HSD2, pH 7.4, 27°C Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.1.1.145 7.4
-
 assay at Homo sapiens
1.1.1.270 7.4
-
 assay at Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
1.1.1.270 NAD+
-
 Homo sapiens
1.1.1.270 NADH
-
 Homo sapiens

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
1.1.1.145 0.00001
-
 trilostane pH 7.4, 27°C, wild-tpye 3beta-HSD1 Homo sapiens
1.1.1.145 0.00002
-
 trilostane pH 7.4, 27°C, mutant R195R Homo sapiens
1.1.1.145 0.0001
-
 trilostane pH 7.4, 27°C, wild-tpye 3beta-HSD2 Homo sapiens
1.1.1.145 0.00022
-
 trilostane pH 7.4, 27°C, mutant R195P Homo sapiens
1.1.1.270 0.0001
-
 trilostane 3beta-HSD1 wild-type, pH 7.4, 27°C Homo sapiens
1.1.1.270 0.00019
-
 trilostane 3beta-HSD2 mutant P195R, pH 7.4, 27°C Homo sapiens
1.1.1.270 0.0016
-
 trilostane 3beta-HSD2 wild-type, pH 7.4, 27°C Homo sapiens
1.1.1.270 0.00256
-
 trilostane 3beta-HSD1 mutant R195P, pH 7.4, 27°C Homo sapiens

General Information

EC Number General Information Comment Organism
1.1.1.270 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
1.1.1.270 metabolism the enzyme catalyzes the first step in the conversion of dehydroepiandrosterone to estradiol Homo sapiens
1.1.1.270 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

kcat/KM [mM/s]

EC Number kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
1.1.1.145 0.83
-
 NAD+ mutant E192A, pH 7.4, 27°C Homo sapiens
1.1.1.145 1
-
 NAD+ mutant D61N, pH 7.4, 27°C Homo sapiens
1.1.1.145 1
-
 dehydroepiandrosterone mutant E192A, pH 7.4, 27°C Homo sapiens
1.1.1.145 1.33
-
 NAD+ mutant E192A, pH 7.4, 27°C Homo sapiens
1.1.1.145 1.33
-
 NAD+ wild-type 3beta-HSD2, pH 7.4, 27°C Homo sapiens
1.1.1.145 1.66
-
 NAD+ wild-type 3beta-HSD1, pH 7.4, 27°C Homo sapiens
1.1.1.145 3.16
-
 NAD+ mutant R195R, pH 7.4, 27°C Homo sapiens
1.1.1.145 4.83
-
 NAD+ mutant R195P, pH 7.4, 27°C Homo sapiens
1.1.1.145 7.33
-
 dehydroepiandrosterone mutant E192A, pH 7.4, 27°C Homo sapiens
1.1.1.145 7.33
-
 dehydroepiandrosterone wild-type 3beta-HSD2, pH 7.4, 27°C Homo sapiens
1.1.1.145 7.66
-
 16beta-hydroxy-dehydroepiandrosterone wild-type 3beta-HSD2, pH 7.4, 27°C Homo sapiens
1.1.1.145 7.83
-
 16alpha-hydroxy-dehydroepiandrosterone mutant R195P, pH 7.4, 27°C Homo sapiens
1.1.1.145 10
-
 dehydroepiandrosterone mutant D61N, pH 7.4, 27°C Homo sapiens
1.1.1.145 10.16
-
 16alpha-hydroxy-dehydroepiandrosterone wild-type 3beta-HSD2, pH 7.4, 27°C Homo sapiens
1.1.1.145 10.33
-
 16beta-hydroxy-dehydroepiandrosterone mutant R195P, pH 7.4, 27°C Homo sapiens
1.1.1.145 11.21
-
 dehydroepiandrosterone mutant R195P, pH 7.4, 27°C Homo sapiens
1.1.1.145 12.16
-
 dehydroepiandrosterone mutant R195R, pH 7.4, 27°C Homo sapiens
1.1.1.145 14.83
-
 dehydroepiandrosterone wild-type 3beta-HSD1, pH 7.4, 27°C Homo sapiens
1.1.1.145 15
-
 16alpha-hydroxy-dehydroepiandrosterone wild-type 3beta-HSD1, pH 7.4, 27°C Homo sapiens
1.1.1.145 19.1
-
 16alpha-hydroxy-dehydroepiandrosterone mutant R195R, pH 7.4, 27°C Homo sapiens
1.1.1.145 34.5
-
 16beta-hydroxy-dehydroepiandrosterone wild-type 3beta-HSD1, pH 7.4, 27°C Homo sapiens
1.1.1.145 35.5
-
 16beta-hydroxy-dehydroepiandrosterone mutant R195R, pH 7.4, 27°C Homo sapiens
1.1.1.145 106
-
 NADH mutant D61N, pH 7.4, 27°C Homo sapiens
1.1.1.145 106
-
 NADH mutant E192A, pH 7.4, 27°C Homo sapiens
1.1.1.145 125
-
 NADH mutant E192A, pH 7.4, 27°C Homo sapiens
1.1.1.145 131
-
 NADH wild-type 3beta-HSD2, pH 7.4, 27°C Homo sapiens
1.1.1.145 163
-
 NADH wild-type 3beta-HSD1, pH 7.4, 27°C Homo sapiens
1.1.1.145 271
-
 NADH mutant R195R, pH 7.4, 27°C Homo sapiens
1.1.1.145 280
-
 NADH mutant R195P, pH 7.4, 27°C Homo sapiens