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Literature summary for 1.1.1.50 extracted from

  • Trauger, J.W.; Jiang, A.; Stearns, B.A.; LoGrasso, P.V.
    Kinetics of allopregnanolone formation catalyzed by human 3alpha-hydroxysteroid dehydrogenase type III (AKR1C2) (2002), Biochemistry, 41, 13451-13459.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
fluoxetine activates allopregnanolone formation in vivo, not in vitro at a concentration up to 0.05 mM, therefore in vivo activation is probably not realized by enzyme activation but a different mechanism Homo sapiens
additional information no in vitro activation by paroxetine, sertraline, norfluoxetine, carbamazepine, clozapine, flurbiprofen, and sulfobromophthalein at a concentration up to 0.05 mM Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
from human cDNA library, expression as GST-fusion protein in Escherichia coli strain BL21(DE3) Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
ursodeoxycholate forward reaction: competitive against 5alpha-dihydroprogesteroneand noncompetitive against NADPH, reverse reaction: competitive against allopregnanolone and noncompetitive against NADP+ Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information steady-state kinetics, ternary complex, sequential, kinetic mechanism of allopregnanolone synthesis with the cofactor binding before the steroid and leaving after it Homo sapiens
0.00007
-
NADPH pH 7.0, 25°C Homo sapiens
0.00023
-
NADP+ pH 7.0, 25°C Homo sapiens
0.00051
-
5beta-dihydroprogesterone pH 7.0, 37°C Homo sapiens
0.0015
-
allopregnanolone pH 7.0, 25°C Homo sapiens
0.0018
-
5alpha-dihydroprogesterone pH 7.0, 25°C Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
5alpha-dihydroprogesterone + NADPH + H+ Homo sapiens last step in neurosteroid allopregnanolone biosynthesis 3alpha,5alpha-3-hydroxypregnan-20-one + NADP+
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
type III enzyme
-

Purification (Commentary)

Purification (Comment) Organism
recombinant GST-fusion protein from Escherichia coli by affinity chromatography on a glutathione resin, cleavage of the GST-tag by thrombin Homo sapiens

Reaction

Reaction Comment Organism Reaction ID
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+ reaction mechanism Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
5alpha-dihydroprogesterone + NADPH + H*
-
Homo sapiens 3alpha,5alpha-3-hydroxypregnan-20-one + 5alpha,20alpha-tetrahydroprogesterone + NADP+
-
?
5alpha-dihydroprogesterone + NADPH + H+ last step in neurosteroid allopregnanolone biosynthesis Homo sapiens 3alpha,5alpha-3-hydroxypregnan-20-one + NADP+
-
?
5beta-dihydroprogesterone + NADPH + H+ preferred substrate Homo sapiens 3alpha,5beta-3-hydroxypregnan-20-one + NADP+
-
?

Synonyms

Synonyms Comment Organism
3alpha-HSD
-
Homo sapiens
3alpha-hydroxysteroid dehydrogenase
-
Homo sapiens
AKR1C2
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
assay at, both reaction directions Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.00017
-
NADP+ pH 7.0, 25°C Homo sapiens
0.00017
-
allopregnanolone pH 7.0, 25°C Homo sapiens
0.003
-
NADPH pH 7.0, 25°C Homo sapiens
0.003
-
5alpha-dihydroprogesterone pH 7.0, 25°C Homo sapiens
0.0167
-
5beta-dihydroprogesterone pH 7.0, 37°C Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7
-
assay at, both reaction directions Homo sapiens

Cofactor

Cofactor Comment Organism Structure
NADPH
-
Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
additional information
-
additional information inhibition kinetics Homo sapiens
0.000027
-
ursodeoxycholate pH 7.0, 25°C, versus allopregnanolone Homo sapiens
0.000086
-
ursodeoxycholate pH 7.0, 25°C, versus NADP+ Homo sapiens
0.00021
-
ursodeoxycholate pH 7.0, 25°C, versus 5alpha-dihydroprogesterone Homo sapiens
0.00055
-
ursodeoxycholate pH 7.0, 25°C, versus NADPH Homo sapiens