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Literature summary for 1.1.1.145 extracted from

  • Thomas, J.L.; Mason, J.I.; Brandt, S.; Spencer, B.R., Jr.; Norris, W.
    Structure/function relationships responsible for the kinetic differences between human type 1 and type 2 3beta-hydroxysteroid dehydrogenase and for the catalysis of the type 1 activity (2002), J. Biol. Chem., 277, 42795-42801.
    View publication on PubMed
Search for more literature for 1.1.1.145

Cloned(Commentary)

Cloned (Comment) Organism
expression in Sf9 cells Homo sapiens
expression of soluble wild-type and mutant isozyme 3beta-HSD1 in Spodoptera frugiperda Sf9 cells using the baculovirus transfection system Homo sapiens
expression of soluble wild-type and mutant isozyme 3beta-HSD2 in Spodoptera frugiperda Sf9 cells using the baculovirus transfection system Homo sapiens

Protein Variants

Protein Variants Comment Organism
H154F no activity Homo sapiens
H156Y 194% of wild-type activity Homo sapiens
H156Y site-directed mutagenesis of isozyme 1, construction of a chimeric Y154-P-H156-S-K158 motif of isozymes 1 and 2, the mutant shows altered kinetics compared to the wild-type isozyme 1, the kinetics are similar to those of isozyme 2 Homo sapiens
K158Q no activity Homo sapiens
K158Q site-directed mutagenesis of isozyme 1, inactive mutant showing no 3beta-hydroxysteroid dehydrogenase activity, but reduced isomerase activity Homo sapiens
K273Q no activity Homo sapiens
K273Q site-directed mutagenesis of isozyme 1, inactive mutant showing no 3beta-hydroxysteroid dehydrogenase activity, but reduced isomerase activity Homo sapiens
Y154F site-directed mutagenesis of isozyme 1, inactive mutant showing no 3beta-hydroxysteroid dehydrogenase activity, but reduced isomerase activity Homo sapiens
Y269S no activity Homo sapiens
Y269S site-directed mutagenesis of isozyme 1, inactive mutant showing no 3beta-hydroxysteroid dehydrogenase activity, but reduced isomerase activity Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
epostane inhibits the 3beta-HSD activity of the wild-type 1 isozyme with 14–17fold greater affinity compared to the wild-type 2 isozyme and mutant H156Y; inhibits the 3beta-HSD activity of the wild-type 1 isozyme with 14–17fold greater affinity compared to the wild-type 2 isozyme and mutant H156Y Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
 additional information kinetics recombinant wild-type isozyme and mutant H165Y, kinetics for the DELTA-5-3-ketosteroid isomerase, EC 5.3.3.1, activity Homo sapiens
additional information
-
 additional information kinetics recombinant wild-type isozymes and mutant H165Y, kinetics for the DELTA-5-3-ketosteroid isomerase, EC 5.3.3.1, activity Homo sapiens
0.0028
-
 pregnenolone 27°C, pH 7.4 Homo sapiens
0.0035
-
 17alpha-hydroxypregnenolone 27°C, pH 7.4 Homo sapiens
0.0037
-
 dehydroepiandrosterone 27°C, pH 7.4 Homo sapiens
0.0037
-
 dehydroepiandrosterone pH 7.4, 27°C, recombinant wild-type isozyme 3beta-HSD1 Homo sapiens
0.018
-
 17alpha-hydroxypregnenolone 27°C, pH 7.4 Homo sapiens
0.025
-
 NAD+ 27°C, pH 7.4, H156Y mutant 3beta-HSD1 Homo sapiens
0.034
-
 NAD+ 27°C, pH 7.4 Homo sapiens
0.042
-
 dehydroepiandrosterone 27°C, pH 7.4, H156Y mutant 3beta-HSD1 Homo sapiens
0.0424
-
 dehydroepiandrosterone pH 7.4, 27°C, recombinant mutant H156Y Homo sapiens
0.047
-
 dehydroepiandrosterone 27°C, pH 7.4 Homo sapiens
0.0473
-
 dehydroepiandrosterone pH 7.4, 27°C, recombinant wild-type isozyme 3beta-HSD2 Homo sapiens
0.05
-
 pregnenolone 27°C, pH 7.4 Homo sapiens
0.086
-
 NAD+ 27°C, pH 7.4 Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
17alpha-hydroxypregnenolone + NAD+ Homo sapiens
-
 17alpha-hydroxy-pregn-5-en-3,20-dione + NADH
-
 ?
dehydroepiandrosterone + NAD+ Homo sapiens
-
 androst-5-en-3,17-dione + NADH + H+
-
 ?
dehydroepiandrosterone + NAD+ Homo sapiens isozyme type 1 ?
-
 ?
additional information Homo sapiens the enzyme is essential for biosynthesis of all classes of steroid hormones, pathway overview ?
-
 ?
pregnenolone + NAD+ Homo sapiens
-
 pregn-5-en-3,20-dione + NADH + H+
-
 ?
pregnenolone + NAD+ Homo sapiens isozyme type 2 progesterone + NADH + H+
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Homo sapiens P14060 3beta-HSD1
-
Homo sapiens P26439 3beta-HSD2
-

Purification (Commentary)

Purification (Comment) Organism
recombinant 3beta-HSD1 Homo sapiens

Reaction

Reaction Comment Organism Reaction ID
a 3beta-hydroxy-DELTA5-steroid + NAD+ = a 3-oxo-DELTA5-steroid + NADH + H+ catalytic residues are Lys159 and Tyr154, structure/function analysis of isozyme 1 Homo sapiens
a
a 3beta-hydroxy-DELTA5-steroid + NAD+ = a 3-oxo-DELTA5-steroid + NADH + H+ catalytic residues are Lys159 and Tyr154, structure/function analysis of isozyme 2 Homo sapiens
a

Source Tissue

Source Tissue Comment Organism Textmining
adrenal cortex isozyme type 2 Homo sapiens
-
placenta isozyme type 1 Homo sapiens
-

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
additional information
-
-
 Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
17alpha-hydroxypregnenolone + NAD+
-
 Homo sapiens 17alpha-hydroxy-pregn-5-en-3,20-dione + NADH
-
 ?
dehydroepiandrosterone + NAD+
-
 Homo sapiens androst-5-en-3,17-dione + NADH + H+
-
 ?
dehydroepiandrosterone + NAD+
-
 Homo sapiens ?
-
 ?
dehydroepiandrosterone + NAD+ isozyme type 1 Homo sapiens ?
-
 ?
additional information the enzyme is essential for biosynthesis of all classes of steroid hormones, pathway overview Homo sapiens ?
-
 ?
additional information bifunctional enzyme that also catalyzes the reaction of the DELTA-5-3-ketosteroid isomerase, EC 5.3.3.1 Homo sapiens ?
-
 ?
pregnenolone + NAD+
-
 Homo sapiens pregn-5-en-3,20-dione + NADH + H+
-
 ?
pregnenolone + NAD+ isozyme type 2 Homo sapiens progesterone + NADH + H+
-
 ?

Synonyms

Synonyms Comment Organism
3beta-HSD1
-
 Homo sapiens
3beta-HSD22
-
 Homo sapiens
3beta-hydroxysteroid dehydrogenase type 2
-
 Homo sapiens
3beta-hydroxysteroid dehydrogenase type1
-
 Homo sapiens
type 1 3beta-hydroxysteroid dehydrogenase
-
 Homo sapiens
type 2 3beta-hydroxysteroid dehydrogenase
-
 Homo sapiens

Temperature Optimum [°C]

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

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.06
-
 dehydroepiandrosterone 27°C, pH 7.4 Homo sapiens
0.062
-
 dehydroepiandrosterone pH 7.4, 27°C, recombinant wild-type isozyme 3beta-HSD1 Homo sapiens
0.07
-
 NAD+ 27°C, pH 7.4 Homo sapiens
0.08
-
 NAD+ 27°C, pH 7.4, H156Y mutant 3beta-HSD1 Homo sapiens
0.115
-
 dehydroepiandrosterone pH 7.4, 27°C, recombinant wild-type isozyme 3beta-HSD2 Homo sapiens
0.12
-
 NAD+ 27°C, pH 7.4 Homo sapiens
0.12
-
 dehydroepiandrosterone 27°C, pH 7.4 Homo sapiens
0.12
-
 dehydroepiandrosterone 27°C, pH 7.4, H156Y mutant 3beta-HSD1 Homo sapiens
0.12
-
 dehydroepiandrosterone pH 7.4, 27°C, recombinant mutant H156Y Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
 assay at Homo sapiens
9.7
-
-
 Homo sapiens

pH Range

pH Minimum pH Maximum Comment Organism
7.4 9.7 structure motif-dependent pH dependence, overview Homo sapiens
7.4
-
 52% of maximal activity Homo sapiens

Cofactor

Cofactor Comment Organism Structure
NAD+
-
 Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.00007
-
 epostane 27°C, pH 7.4 Homo sapiens
0.000071
-
 epostane pH 7.4, 27°C, recombinant wild-type isozyme 3beta-HSD1 Homo sapiens
0.00098
-
 epostane 27°C, pH 7.4 Homo sapiens
0.00098
-
 epostane pH 7.4, 27°C, recombinant wild-type isozyme 3beta-HSD2 Homo sapiens
0.0012
-
 epostane 27°C, pH 7.4, H156Y mutant Homo sapiens