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Literature summary for 1.1.1.145 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

Cloned(Commentary)

Cloned (Comment) Organism
expressed in Sf9 cells using the baculovirus system Homo sapiens

Protein Variants

Protein Variants Comment Organism
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
D61V mutant shows no enzymatic activity Homo sapiens
E192A the E192A mutation causes an 8.2fold increase in Km (dehydroepiandrosterone) and no change in the Km for NAD+ Homo sapiens
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
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
T8A mutant shows almost similar kinetic values as wild-type Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
trilostane
-
Homo sapiens

KM Value [mM]

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

Molecular Weight [Da]

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

Organism

Organism UniProt Comment Textmining
Homo sapiens P14060
-
-
Homo sapiens P26439
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
16alpha-hydroxy-dehydroepiandrosterone + NAD+
-
Homo sapiens ?
-
?
16alpha-hydroxy-dehydroepiandrosterone + NAD+
-
Homo sapiens ? + NADH
-
?
16beta-hydroxy-dehydroepiandrosterone + NAD+
-
Homo sapiens ?
-
?
16beta-hydroxy-dehydroepiandrosterone + NAD+
-
Homo sapiens ? + NADH
-
?
androst-5-en-3,17-dione + NADH
-
Homo sapiens dehydroepiandrosterone + NAD+
-
r
dehydroepiandrosterone + NAD+
-
Homo sapiens androst-5-en-3,17-dione + NADH + H+
-
?
dehydroepiandrosterone + NAD+
-
Homo sapiens androst-5-en-3,17-dione + NADH + H+
-
r

Synonyms

Synonyms Comment Organism
3beta-HSD1
-
Homo sapiens
3beta-HSD2
-
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
0.02
-
NAD+ mutant E192A, pH 7.4, 27°C Homo sapiens
0.03
-
dehydroepiandrosterone mutant E192A, pH 7.4, 27°C Homo sapiens
0.04
-
dehydroepiandrosterone mutant D61N, pH 7.4, 27°C Homo sapiens
0.04
-
NAD+ mutant E192A, pH 7.4, 27°C Homo sapiens
0.04
-
16beta-hydroxy-dehydroepiandrosterone wild-type 3beta-HSD1, pH 7.4, 27°C Homo sapiens
0.05
-
16beta-hydroxy-dehydroepiandrosterone mutant R195R, pH 7.4, 27°C Homo sapiens
0.05
-
NAD+ wild-type 3beta-HSD1, pH 7.4, 27°C Homo sapiens
0.05
-
dehydroepiandrosterone wild-type 3beta-HSD1, pH 7.4, 27°C Homo sapiens
0.06
-
NAD+ mutant D61N, pH 7.4, 27°C Homo sapiens
0.06
-
dehydroepiandrosterone mutant E192A, pH 7.4, 27°C Homo sapiens
0.07
-
16alpha-hydroxy-dehydroepiandrosterone mutant R195R, pH 7.4, 27°C Homo sapiens
0.09
-
dehydroepiandrosterone mutant R195R, pH 7.4, 27°C Homo sapiens
0.09
-
16alpha-hydroxy-dehydroepiandrosterone wild-type 3beta-HSD1, pH 7.4, 27°C Homo sapiens
0.1
-
NAD+ mutant R195P, pH 7.4, 27°C Homo sapiens
0.11
-
NAD+ wild-type 3beta-HSD2, pH 7.4, 27°C Homo sapiens
0.12
-
dehydroepiandrosterone mutant R195P, pH 7.4, 27°C Homo sapiens
0.14
-
dehydroepiandrosterone wild-type 3beta-HSD2, pH 7.4, 27°C Homo sapiens
0.14
-
16beta-hydroxy-dehydroepiandrosterone wild-type 3beta-HSD2, pH 7.4, 27°C Homo sapiens
0.15
-
16beta-hydroxy-dehydroepiandrosterone mutant R195P, pH 7.4, 27°C Homo sapiens
0.15
-
16alpha-hydroxy-dehydroepiandrosterone mutant R195P, pH 7.4, 27°C Homo sapiens
0.15
-
16alpha-hydroxy-dehydroepiandrosterone wild-type 3beta-HSD2, pH 7.4, 27°C Homo sapiens
0.17
-
NAD+ mutant R195R, pH 7.4, 27°C Homo sapiens
0.31
-
NADH mutant E192A, pH 7.4, 27°C Homo sapiens
0.69
-
NADH mutant E192A, pH 7.4, 27°C Homo sapiens
0.75
-
NADH wild-type 3beta-HSD1, pH 7.4, 27°C Homo sapiens
0.76
-
NADH mutant D61N, pH 7.4, 27°C Homo sapiens
1.03
-
NADH mutant R195P, pH 7.4, 27°C Homo sapiens
1.49
-
NADH mutant R195R, pH 7.4, 27°C Homo sapiens
1.65
-
NADH wild-type 3beta-HSD2, pH 7.4, 27°C Homo sapiens

pH Optimum

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

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.00001
-
trilostane pH 7.4, 27°C, wild-tpye 3beta-HSD1 Homo sapiens
0.00002
-
trilostane pH 7.4, 27°C, mutant R195R Homo sapiens
0.0001
-
trilostane pH 7.4, 27°C, wild-tpye 3beta-HSD2 Homo sapiens
0.00022
-
trilostane pH 7.4, 27°C, mutant R195P Homo sapiens

kcat/KM [mM/s]

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