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Literature summary 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

EC Number Activating Compound Comment Organism Structure
1.1.1.50 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
1.1.1.50 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)

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

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.1.1.50 ursodeoxycholate forward reaction: competitive against 5alpha-dihydroprogesteroneand noncompetitive against NADPH, reverse reaction: competitive against allopregnanolone and noncompetitive against NADP+ Homo sapiens
1.1.1.357 ursodeoxycholate micromolar inhibitor, competitive inhibitor versus 5alpha-dihydroprogesterone and uncompetitive inhibitor versus NADPH Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.1.1.50 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
1.1.1.50 0.00007
-
 NADPH pH 7.0, 25°C Homo sapiens
1.1.1.50 0.00023
-
 NADP+ pH 7.0, 25°C Homo sapiens
1.1.1.50 0.00051
-
 5beta-dihydroprogesterone pH 7.0, 37°C Homo sapiens
1.1.1.50 0.0015
-
 allopregnanolone pH 7.0, 25°C Homo sapiens
1.1.1.50 0.0018
-
 5alpha-dihydroprogesterone pH 7.0, 25°C Homo sapiens
1.1.1.357 0.00007
-
 NADPH in 100 mM potassium phosphate, pH 7.0, at 25°C Homo sapiens
1.1.1.357 0.00023
-
 NADP+ in 100 mM potassium phosphate, pH 7.0, at 25°C Homo sapiens
1.1.1.357 0.0015
-
 allopregnanolone in 100 mM potassium phosphate, pH 7.0, at 25°C Homo sapiens
1.1.1.357 0.0018
-
 5alpha-dihydroprogesterone in 100 mM potassium phosphate, pH 7.0, at 25°C Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.1.1.50 5alpha-dihydroprogesterone + NADPH + H+ Homo sapiens last step in neurosteroid allopregnanolone biosynthesis 3alpha,5alpha-3-hydroxypregnan-20-one + NADP+
-
 ?
1.1.1.357 5alpha-dihydroprogesterone + NADPH + H+ Homo sapiens
-
 allopregnanolone + 5alpha,20alpha-tetrahydroprogesterone + NADP+
-
 r
1.1.1.357 5beta-dihydroprogesterone + NADPH + H+ Homo sapiens
-
 pregnanolone + NADP+
-
 r
1.1.1.357 allopregnanolone + 5alpha,20alpha-tetrahydroprogesterone + NADP+ Homo sapiens
-
 5alpha-dihydroprogesterone + NADPH + H+
-
 r

Organism

EC Number Organism UniProt Comment Textmining
1.1.1.50 Homo sapiens
-
 type III enzyme
-
1.1.1.357 Homo sapiens P52895
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.1.1.50 recombinant GST-fusion protein from Escherichia coli by affinity chromatography on a glutathione resin, cleavage of the GST-tag by thrombin Homo sapiens
1.1.1.357
-
 Homo sapiens

Reaction

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

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.1.1.50 5alpha-dihydroprogesterone + NADPH + H*
-
 Homo sapiens 3alpha,5alpha-3-hydroxypregnan-20-one + 5alpha,20alpha-tetrahydroprogesterone + NADP+
-
 ?
1.1.1.50 5alpha-dihydroprogesterone + NADPH + H+ last step in neurosteroid allopregnanolone biosynthesis Homo sapiens 3alpha,5alpha-3-hydroxypregnan-20-one + NADP+
-
 ?
1.1.1.50 5beta-dihydroprogesterone + NADPH + H+ preferred substrate Homo sapiens 3alpha,5beta-3-hydroxypregnan-20-one + NADP+
-
 ?
1.1.1.357 5alpha-dihydroprogesterone + NADPH + H+
-
 Homo sapiens allopregnanolone + 5alpha,20alpha-tetrahydroprogesterone + NADP+
-
 r
1.1.1.357 5beta-dihydroprogesterone + NADPH + H+
-
 Homo sapiens pregnanolone + NADP+
-
 r
1.1.1.357 allopregnanolone + 5alpha,20alpha-tetrahydroprogesterone + NADP+
-
 Homo sapiens 5alpha-dihydroprogesterone + NADPH + H+
-
 r

Synonyms

EC Number Synonyms Comment Organism
1.1.1.50 3alpha-HSD
-
 Homo sapiens
1.1.1.50 3alpha-hydroxysteroid dehydrogenase
-
 Homo sapiens
1.1.1.50 AKR1C2
-
 Homo sapiens
1.1.1.357 3alpha-HSD type III
-
 Homo sapiens
1.1.1.357 3alpha-hydroxysteroid dehydrogenase type III
-
 Homo sapiens
1.1.1.357 AKR1C2
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.1.1.50 25
-
 assay at, both reaction directions Homo sapiens

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
1.1.1.50 0.00017
-
 NADP+ pH 7.0, 25°C Homo sapiens
1.1.1.50 0.00017
-
 allopregnanolone pH 7.0, 25°C Homo sapiens
1.1.1.50 0.003
-
 NADPH pH 7.0, 25°C Homo sapiens
1.1.1.50 0.003
-
 5alpha-dihydroprogesterone pH 7.0, 25°C Homo sapiens
1.1.1.50 0.0167
-
 5beta-dihydroprogesterone pH 7.0, 37°C Homo sapiens
1.1.1.357 0.000017
-
 allopregnanolone in 100 mM potassium phosphate, pH 7.0, at 25°C Homo sapiens
1.1.1.357 0.003
-
 5alpha-dihydroprogesterone in 100 mM potassium phosphate, pH 7.0, at 25°C Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.1.1.50 7
-
 assay at, both reaction directions Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
1.1.1.50 NADPH
-
 Homo sapiens
1.1.1.357 NADH
-
 Homo sapiens
1.1.1.357 NADPH
-
 Homo sapiens

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
1.1.1.50 additional information
-
 additional information inhibition kinetics Homo sapiens
1.1.1.50 0.000027
-
 ursodeoxycholate pH 7.0, 25°C, versus allopregnanolone Homo sapiens
1.1.1.50 0.000086
-
 ursodeoxycholate pH 7.0, 25°C, versus NADP+ Homo sapiens
1.1.1.50 0.00021
-
 ursodeoxycholate pH 7.0, 25°C, versus 5alpha-dihydroprogesterone Homo sapiens
1.1.1.50 0.00055
-
 ursodeoxycholate pH 7.0, 25°C, versus NADPH Homo sapiens