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Literature summary extracted from

  • Pham, J.H.; Will, C.M.; Mack, V.L.; Halbert, M.; Conner, E.A.; Bucholtz, K.M.; Thomas, J.L.
    Structure-function relationships for the selective inhibition of human 3beta-hydroxysteroid dehydrogenase type 1 by a novel androgen analog (2017), J. Steroid Biochem. Mol. Biol., 174, 257-264 .
    View publication on PubMed

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.1.1.145 expression of the chimeric S194G-1 mutant of the enzyme (3beta-HSD1) Homo sapiens
1.1.1.270 the cDNA that encodes the mutant 3beta-HSD1 enzymes S194G-1 and R195P-1 are generated via double-stranded, PCR-based mutagenesis and inserted into baculovirus. The recombinant baculovirus system successfully expresses the mutant S194G-1 and R195P-1 enzyme proteins in Sf9 cells with the wild-type 3beta-HSD1 as the control Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
1.1.1.145 R195P 16-cyano-17-keto-trilostane inhibits the chimeric R195P-1 mutant of the enzyme (3beta-HSD1) with a noncompetitive mode compared to competitive inhibition of the wild-type enzyme (3beta-HSD1) Homo sapiens
1.1.1.145 S194G 16-cyano-17-keto-trilostane and trilostane inhibits the chimeric S194G-1 mutant of the enzyme (3beta-HSD1) with a noncompetitive mode compared to competitive inhibition of the wild-type enzyme (3beta-HSD1) Homo sapiens
1.1.1.270 R195P 2,16-dicyano-4,5-epoxy-androstane-3,17-dione competitively inhibits S194G-1 Homo sapiens
1.1.1.270 S194G trilostane inhibits chimeric S194G-1 mutant (Ki: 0.00067 mM) with a noncompetitive mode compared to its 6.7fold higher affinity, competitive inhibition of 3beta-HSD1. 2,16-Dicyano-4,5-epoxy-androstane-3,17-dione inhibits S194G-1 with a 6.3fold higher Ki (0.0295 mM) than measured for 3beta-HSD1 (Ki: 0.0047 mM) but with the same competitive mode for both enzyme species Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.1.1.145 16-cyano-17-keto-trilostane i.e 2,16-dicyano-4,5-epoxy-androstane-3,17-dione. Competitive, selective inhibitor of wild-type enzyme and chimeric S194G-1 mutant of the enzyme (3beta-HSD1). Noncompetitive inhibitor of chimeric R195P-1 mutant of the enzyme. Selective inhibition of 3beta-HSD1 may prevent spontaneous premature birth; i.e 2,16-dicyano-4,5-epoxy-androstane-3,17-dione. noncompetitive inhibitor; selective inhibitor Homo sapiens
1.1.1.145 2,16-dicyano-4,5-epoxy-androstane-3,17-dione competitively inhibits 3beta-HSD1 Homo sapiens
1.1.1.145 trilostane noncompetitive inhibitor; noncompetitive inhibitor of chimeric S194G-1 mutant and chimeric R195P-1 mutant of the enzyme (3beta-HSD1). Competitive inhibition of wild-type enzyme Homo sapiens
1.1.1.270 16-cyano-17-keto-trilostane selective inhibitor Homo sapiens
1.1.1.270 2,16-dicyano-4,5-epoxy-androstane-3,17-dione competitively inhibits 3beta-HSD1 Homo sapiens
1.1.1.270 trilostane
-
 Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.1.1.145 0.0037
-
 dehydroepiandrosterone pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.145 0.0107
-
 dehydroepiandrosterone pH 7.4, 27°C, chimeric R195P-1 mutant of the enzyme (3beta-HSD1) Homo sapiens
1.1.1.145 0.0124
-
 dehydroepiandrosterone pH 7.4, 27°C, chimeric S194G-1 mutant of the enzyme (3beta-HSD1) Homo sapiens
1.1.1.145 0.0156
-
 dehydroepiandrosterone pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.145 0.0205
-
 NAD+ pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.145 0.0244
-
 NAD+ pH 7.4, 27°C, chimeric R195P-1 mutant of the enzyme (3beta-HSD1) Homo sapiens
1.1.1.145 0.0341
-
 NAD+ pH 7.4, 27°C, chimeric S194G-1 mutant of the enzyme (3beta-HSD1) Homo sapiens
1.1.1.145 0.0863
-
 NAD+ pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.270 0.0037
-
 dehydroepiandrosterone pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.270 0.0107
-
 dehydroepiandrosterone pH 7.4, 27°C, chimeric 195P-1 mutant Homo sapiens
1.1.1.270 0.0124
-
 dehydroepiandrosterone pH 7.4, 27°C, chimeric S194G-1 mutant Homo sapiens
1.1.1.270 0.0205
-
 NAD+ pH 7.4, 27°C, chimeric 195P-1 mutant Homo sapiens
1.1.1.270 0.0244
-
 NAD+ pH 7.4, 27°C, chimeric S194G-1 mutant Homo sapiens
1.1.1.270 0.0341
-
 NAD+ pH 7.4, 27°C, wild-type enzyme 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 P14060
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.1.1.145 purification of the chimeric S194G-1 mutant of the enzyme (3beta-HSD1) Homo sapiens
1.1.1.270
-
 Homo sapiens

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.1.1.145 adrenal gland 3beta-HSD21 is selectively expressed in adrenal glands and ovaries Homo sapiens
-
1.1.1.145 adrenal gland selectively expressed in adrenal glands and ovaries Homo sapiens
-
1.1.1.145 breast cancer cell
-
 Homo sapiens
-
1.1.1.145 mammary gland
-
 Homo sapiens
-
1.1.1.145 ovary
-
 Homo sapiens
-
1.1.1.145 ovary 3beta-HSD21 is selectively expressed in adrenal glands and ovaries Homo sapiens
-
1.1.1.145 placenta
-
 Homo sapiens
-
1.1.1.270 breast cancer cell 3beta-HSD1 is selectively expressed in human placenta, mammary glands and breast tumors in women Homo sapiens
-
1.1.1.270 mammary gland 3beta-HSD1 is selectively expressed in human placenta, mammary glands and breast tumors in women Homo sapiens
-
1.1.1.270 placenta 3beta-HSD1 is selectively expressed in human placenta, mammary glands and breast tumors in women Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.1.1.145 dehydroepiandrosterone + NAD+
-
 Homo sapiens 5-androstene-3,17-dione + NADH + H+
-
 ?
1.1.1.145 dehydroepiandrosterone + NAD+
-
 Homo sapiens androstenedione + NADH + H+
-
 ?
1.1.1.270 dehydroepiandrosterone + NAD+
-
 Homo sapiens androstenedione + NADH + H+
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.1.1.145 3beta-HSD1
-
 Homo sapiens
1.1.1.145 3beta-HSD2
-
 Homo sapiens
1.1.1.145 3beta-hydroxysteroid dehydrogenase type 1
-
 Homo sapiens
1.1.1.270 3beta-HSD1
-
 Homo sapiens
1.1.1.270 3beta-hydroxysteroid dehydrogenase type 1
-
 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 0.04
-
 NAD+ pH 7.4, 27°C, chimeric R195P-1 mutant of the enzyme (3beta-HSD1) Homo sapiens
1.1.1.145 0.055
-
 dehydroepiandrosterone pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.145 0.06
-
 NAD+ pH 7.4, 27°C, chimeric S194G-1 mutant of the enzyme (3beta-HSD1) Homo sapiens
1.1.1.145 0.1
-
 NAD+ pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.145 0.118
-
 NAD+ pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.145 0.12
-
 NAD+ pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.145 0.128
-
 dehydroepiandrosterone pH 7.4, 27°C, chimeric R195P-1 mutant of the enzyme (3beta-HSD1) Homo sapiens
1.1.1.145 0.13
-
 dehydroepiandrosterone pH 7.4, 27°C, chimeric S194G-1 mutant of the enzyme (3beta-HSD1) Homo sapiens
1.1.1.145 0.145
-
 dehydroepiandrosterone pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.270 0.04
-
 NAD+ pH 7.4, 27°C, chimeric S194G-1 mutant Homo sapiens
1.1.1.270 0.055
-
 dehydroepiandrosterone pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.270 0.058
-
 NAD+ pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.270 0.1
-
 NAD+ pH 7.4, 27°C, chimeric 195P-1 mutant Homo sapiens
1.1.1.270 0.1283
-
 dehydroepiandrosterone pH 7.4, 27°C, chimeric 195P-1 mutant Homo sapiens
1.1.1.270 0.13
-
 dehydroepiandrosterone pH 7.4, 27°C, chimeric S194G-1 mutant Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
1.1.1.145 NAD+
-
 Homo sapiens

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
1.1.1.145 0.0001
-
 trilostane pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.145 0.00067
-
 trilostane pH 7.4, 27°C, chimeric S194G-1 mutant of the enzyme (3beta-HSD1) Homo sapiens
1.1.1.145 0.0016
-
 trilostane pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.145 0.0016
-
 16-cyano-17-keto-trilostane pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.145 0.00256
-
 trilostane pH 7.4, 27°C, chimeric R195P-1 mutant of the enzyme (3beta-HSD1) Homo sapiens
1.1.1.145 0.0047
-
 16-cyano-17-keto-trilostane pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.145 0.0295
-
 16-cyano-17-keto-trilostane pH 7.4, 27°C, chimeric S194G-1 mutant of the enzyme (3beta-HSD1) Homo sapiens
1.1.1.145 0.0307
-
 trilostane pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.145 0.0307
-
 2,16-dicyano-4,5-epoxy-androstane-3,17-dione pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.145 0.0413
-
 16-cyano-17-keto-trilostane pH 7.4, 27°C, chimeric R195P-1 mutant of the enzyme (3beta-HSD1) Homo sapiens
1.1.1.270 0.0001
-
 trilostane pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.270 0.00067
-
 trilostane pH 7.4, 27°C, chimeric S194G-1 mutant Homo sapiens
1.1.1.270 0.00256
-
 trilostane pH 7.4, 27°C, chimeric 195P-1 mutant Homo sapiens
1.1.1.270 0.0047
-
 2,16-dicyano-4,5-epoxy-androstane-3,17-dione pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.270 0.0295
-
 2,16-dicyano-4,5-epoxy-androstane-3,17-dione pH 7.4, 27°C, chimeric S194G-1 mutant Homo sapiens
1.1.1.270 0.0415
-
 2,16-dicyano-4,5-epoxy-androstane-3,17-dione pH 7.4, 27°C, chimeric 195P-1 mutant Homo sapiens

General Information

EC Number General Information Comment Organism
1.1.1.145 drug target 16-cyano-17-keto-trilostane is a selective inhibitor of 3beta-hydroxysteroid dehydrogenase type 1. Selective inhibition of beta-HSD1 may prevent spontaneous premature birth. Inhibition of 3beta-HSD1 decreases placental estradiol production that promotes labor. The 3beta-HSD1 inhibitor may be administered with 17alpha-hydroxyprogesterone caproate Homo sapiens
1.1.1.270 drug target selective inhibition of 3beta-HSD1 may prevent spontaneous premature birth. Inhibition of 3beta-HSD1 decreases placental estradiol production that promotes labor. The 3beta-HSD1 inhibitor may be administered with 17alpha-hydroxyprogesterone caproate 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 0.176
-
 NAD+ pH 7.4, 27°C, chimeric S194G-1 mutant of the enzyme (3beta-HSD1) Homo sapiens
1.1.1.145 0.93
-
 dehydroepiandrosterone pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.145 1.37
-
 NAD+ pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.145 1.4
-
 NAD+ pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.145 1.64
-
 NAD+ pH 7.4, 27°C, chimeric R195P-1 mutant of the enzyme (3beta-HSD1) Homo sapiens
1.1.1.145 4.8
-
 NAD+ pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.145 9.29
-
 dehydroepiandrosterone pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.145 10.48
-
 dehydroepiandrosterone pH 7.4, 27°C, chimeric S194G-1 mutant of the enzyme (3beta-HSD1) Homo sapiens
1.1.1.145 11.96
-
 dehydroepiandrosterone pH 7.4, 27°C, chimeric R195P-1 mutant of the enzyme (3beta-HSD1) Homo sapiens
1.1.1.145 14.86
-
 dehydroepiandrosterone pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.270 1.64
-
 NAD+ pH 7.4, 27°C, chimeric S194G-1 mutant Homo sapiens
1.1.1.270 1.7
-
 NAD+ pH 7.4, 27°C, wild-type enzyme Homo sapiens
1.1.1.270 4.88
-
 NAD+ pH 7.4, 27°C, chimeric 195P-1 mutant Homo sapiens
1.1.1.270 10.48
-
 dehydroepiandrosterone pH 7.4, 27°C, chimeric S194G-1 mutant Homo sapiens
1.1.1.270 11.99
-
 dehydroepiandrosterone pH 7.4, 27°C, chimeric 195P-1 mutant Homo sapiens
1.1.1.270 14.86
-
 dehydroepiandrosterone pH 7.4, 27°C, wild-type enzyme Homo sapiens