Information on EC 1.1.1.64 - testosterone 17beta-dehydrogenase (NADP+)

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The expected taxonomic range for this enzyme is: Euteleostomi

EC NUMBER
COMMENTARY
1.1.1.64
-
RECOMMENDED NAME
GeneOntology No.
testosterone 17beta-dehydrogenase (NADP+)
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
testosterone + NADP+ = androstenedione + NADPH + H+
show the reaction diagram
4-pro-R-hydrogen atom of NADPH is transferred to the alpha-face of the steroid molecule
-
testosterone + NADP+ = androstenedione + NADPH + H+
show the reaction diagram
4-pro-S-hydrogen atom of NADPH is transferred to the alpha-face of the steroid molecule
-
testosterone + NADP+ = androstenedione + NADPH + H+
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
androgen biosynthesis
-
Metabolic pathways
-
Steroid hormone biosynthesis
-
SYSTEMATIC NAME
IUBMB Comments
17beta-hydroxysteroid:NADP+ 17-oxidoreductase
Also oxidizes 3-hydroxyhexobarbital to 3-oxohexobarbital.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
17-ketoreductase
-
-
-
-
17beta-HSD
O54939
-
17beta-HSD 3
-
-
17beta-HSD type 3
-
-
17beta-HSD type 5
-
-
17beta-HSD-3
-
-
17beta-HSD1
-
-
17beta-HSD3
-
-
17beta-HSD3
P37058
-
17beta-HSD4
-
-
17beta-hydroxysteroid dehydrogenase
-
-
17beta-hydroxysteroid dehydrogenase
O54939
-
17beta-hydroxysteroid dehydrogenase 3
-
-
17beta-hydroxysteroid dehydrogenase type 3
-
-
17beta-hydroxysteroid dehydrogenase type 3
-
-
17beta-hydroxysteroid dehydrogenase type 3
-
-
17beta-hydroxysteroid dehydrogenase type 5
-
-
17beta-hydroxysteroid dehydrogenases type 3
-
-
17betaHSD3
-
-
3beta-hydroxysteroid dehydrogenase type 3
P37058
-
NADP-dependent testosterone-17beta-oxidoreductase
-
-
-
-
type 3 17beta-hydroxysteroid dehydrogenase
-
-
type 5 beta-hydroxysteroid dehydrogenase
P42330
-
additional information
-
the enzyme belongs to the aldo-keto reductase family
CAS REGISTRY NUMBER
COMMENTARY
9028-63-1
-
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
AKR1C3 knockdown is accomplished in cultured adrenal cells (H295R) using small interfering RNA. Decreasing adrenal cell expression of AKR1C3 mRNA and protein inhibit testosterone production in the H295R adrenal cell line
physiological function
-
exposure of HCT-15 cells to cisplatin results in aquisition of cisplatin resistance and concomitant induction of isoform AKR1C3 and aldo-keto reductase AKR1C1 expression. The resistance lowers the sensitivity toward cellular damages evoked by oxidative stress-derived aldehydes, 4-hydroxy-2-nonenal and 4-oxo-2-nonenal that are detoxified by AKR1C1 and AKR1C3. Overexpression of AKR1C1 or AKR1C3 in the parental HCT15 cells mitigates the cytotoxicity of the aldehydes and cisplatin. Knockdown of both AKR1C1 and AKR1C3 in the resistant cells or treatment of the cells with specific inhibitors of the aldo-keto reductases increases the sensitivity to ciplatin toxicity
physiological function
-
isoform 17beta-HSD3-dependent reduction of 4-androstene-3,17-dione is affected by neither coexpression with 11beta-HSD1, EC 1.1.1.146, nor overexpression or knock-down of hexose-6-phosphate dehydrogenase. Knock-down of glucose-6-phosphate dehydrogenase decreases 17beta-HSD3 activity, indicating dependence on cytoplasmic NADPH. Cytoplasmic orientation of isoform 17beta-HSD3 and dependence on glucose-6-phosphate dehydrogenase-generated NADPH explain the lack of a direct functional coupling with the luminal 11beta-HSD1-mediated glucocorticoid metabolism
physiological function
-
in LNCaP and LNCaP-AKR1C3 cells overexpressing isoform AKR1C3, metabolism proceeds via 5alpha-reduction to form 5alpha-androstane-3,17-dione and then (epi)androsterone-3-glucuronide. LNCaP-AKR1C3 cells make significantly higher amounts of testosterone-17beta-glucuronide. When 5alpha-reductase is inhibited by finasteride, the production of testosterone-17beta-glucuronide is further elevated in LNCaP-AKR1C3 cells. When AKR1C3 activity is inhibited with indomethacin the production of testosterone-17beta-glucuronide is significantly decreased. 4-Androstene-3,17-dione treatment stimulates cell proliferation in both cell lines. LNCaP-AKR1C3 cells are resistant to the growth inhibitory properties of finasteride, consistent with the diversion of 4-androstene-3,17-dione metabolism from 5alpha-reduced androgens to increased formation of testosterone
physiological function
-
the two reactions 11beta-HSD1-dehydrogenase, EC 1.1.1.146, and 17beta-HSD3, EC 1.1.1.64, which utilize NADPH are competing for NADPH from the same cofactor pool. 11beta-HSD1-dehydrogenase serves as a NADPH-regenerating system that is tightly coupled in regulating 17beta-HSD3 reaction synthesizing testosterone. A cycle can exist whereby the NADPH produced by 11beta-HSD1 dehydrogenase can drive the reductase activity of 17beta-HSD3 and the NADP+ produced by 17beta-HSD3 and other enzymes involved in testosterone biosynthesis can drive the dehydrogenase activity of 11beta-HSD1
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(S)-alpha-tetralol + NADP+
alpha-tetralone + NADPH + H+ [View the structure]
show the reaction diagram
-
-
-
-
?
(S)-tetralol + NADP+
? + NADPH
show the reaction diagram
-
-
-
-
?
1,2,3,4-tetrahydro-1-naphthol + NADP+
1,2,3,4-tetrahydro-1-naphthone + NADPH
show the reaction diagram
-
isoenzymes 1 and 2
-
r
1-acenaphthenol + NADP+
1-acenaphthenone + NADPH
show the reaction diagram
-
isoenzymes 1 and 2
-
r
11-hydroxy-androstenedione + NADPH
11beta-hydroxy-testosterone
show the reaction diagram
-
-
-
-
?
11-ketoandrostenedione + NADPH
11-ketotestosterone + NADP+
show the reaction diagram
-
-
-
-
?
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
19-nortestosterone + NADP+
19-norandrostenedione + NADPH
show the reaction diagram
-
93% activity compared to testosterone oxidation
-
r
4-oxo-2-nonenal + NADPH + H+
4-hydroxy-2-nonenal + NADP+
show the reaction diagram
-
-
-
-
?
5alpha-androstane-17beta-ol-3-one + NADP+
5alpha-androstane-3,17-dione + NADPH
show the reaction diagram
-
30% activity compared to testosterone oxidation
-
r
5alpha-androstane-3alpha,17beta-diol + NADP+
5alpha-androstane-3alpha-ol-17-one + NADPH
show the reaction diagram
-
93% activity compared to testosterone oxidation, 63% activity compared to testosterone oxidation
-
r
5alpha-androstane-3beta,17beta-diol + NADP+
5alpha-androstane-3beta-ol-17-one + NADPH
show the reaction diagram
-
25% activity compared to testosterone oxidation, 134% activity compared to testosterone oxidation
-
r
5alpha-dihydrotestosterone + NADP+
5alpha-17-oxo-dihydrotestosterone + NADPH
show the reaction diagram
-
isoenzymes 1 and 2
-
r
5beta-androstane-17beta-ol + NADP+
5alpha-androstane-17-one + NADPH
show the reaction diagram
-
117% activity compared to testosterone oxidation
-
r
5beta-androstane-17beta-ol-3-one + NADP+
5beta-androstane-3,17-dione + NADPH
show the reaction diagram
-
330% activity compared to testosterone oxidation
-
r
5beta-androstane-3alpha,17beta-diol + NADP+
5beta-androstane-3alpha-17-one + NADPH
show the reaction diagram
-
-
-
r
5beta-androstane-3alpha,17beta-diol + NADP+
5alpha-androstane-3alpha-ol-17-one + NADPH
show the reaction diagram
-
1180% activity compared to testosterone oxidation
-
r
5beta-androstane-3alpha,17beta-diol + NADP+
5beta-androstane-3alpha-ol-17-one + NADPH
show the reaction diagram
-
-
-
r
5beta-dihydrotestosterone + NADP+
5beta-17-oxo-dihydrotestosterone + NADPH
show the reaction diagram
-
-
-
-
-
5beta-dihydrotestosterone + NADP+
5beta-17-oxo-dihydrotestosterone + NADPH
show the reaction diagram
-
isoenzymes 1 and 2
-
r
9,10-phenanthrenequinone + NADPH
?
show the reaction diagram
-
-
-
-
?
androst-4-ene-3,17-dione + NADPH
testosterone + NADP+
show the reaction diagram
-
-
-
-
?
androst-4-ene-3,17-dione + NADPH
testosterone + NADP+
show the reaction diagram
-
the enzyme plays a central role in the development of the male phenotype. Mutations that inactivate the enzyme give rise to a rare form of male pseudohermaphroditism, referred to as 17beta-HSD-3 deficiency
-
-
?
androst-4-ene-3,17-dione + NADPH
testosterone + NADP+
show the reaction diagram
-
convertion of the weak androgen androstendione into the potent androgen testosterone
-
-
?
androst-4-ene-3,17-dione + NADPH + H+
testosterone + NADP+
show the reaction diagram
-
-
-
-
?
androstanedione + NADPH
dihydrotestosterone + NADP+
show the reaction diagram
-
-
-
-
?
androstenedione + NADPH + H+
testosterone + NADP+
show the reaction diagram
-
-
-
-
?
androstenedione + NADPH + H+
testosterone + NADP+
show the reaction diagram
-
-
-
-
r
androstenedione + NADPH + H+
testosterone + NADP+
show the reaction diagram
-
-
-
-
?
androstenedione + NADPH + H+
testosterone + NADP+
show the reaction diagram
-
-
-
-
?
androstenedione + NADPH + H+
testosterone + NADP+
show the reaction diagram
-
-
-
-
r
androstenedione + NADPH + H+
testosterone + NADP+
show the reaction diagram
O54939
-
-
-
?
androstenedione + NADPH + H+
testosterone + NADP+
show the reaction diagram
-
-
i.e. 4-androsten-17-ol-3-one
-
?
androstenedione + NADPH + H+
testosterone + NADP+
show the reaction diagram
-
the equilibrium state is 92% testosterone to 8% androstenedione
-
-
r
androstenedione + NADPH + H+
testosterone + NADP+
show the reaction diagram
-
the enzyme is involved in biosynthesis of testosterone
-
-
?
androstenedione + NADPH + H+
testosterone + NADP+
show the reaction diagram
-
17beta-HSD3
-
-
?
androstenedione + NADPH + H+
testosterone + NADP+
show the reaction diagram
-
the two reactions 11beta-HSD1-dehydrogenase, EC 1.1.1.146, and 17beta-HSD3, EC 1.1.1.64, which utilize NADPH are competing for NADPH from the same cofactor pool. 11beta-HSD1-dehydrogenase serves as a NADPH-regenerating system that is tightly coupled in regulating 17beta-HSD3 reaction synthesizing testosterone. A cycle can exist whereby the NADPH produced by 11beta-HSD1 dehydrogenase can drive the reductase activity of 17beta-HSD3 and the NADP+ produced by 17beta-HSD3 and other enzymes involved in testosterone biosynthesis can drive the dehydrogenase activity of 11beta-HSD1
i.e. 4-androsten-17beta-ol-3-one
-
?
androsterone + NADPH
androstane-3beta,17beta-diol + NADP+
show the reaction diagram
-
-
-
-
?
benzene dihydrodiol + NADP+
o-benzoquinone + NADPH
show the reaction diagram
-
isoenzymes 1 and 2
-
r
cyclohex-2-en-1-ol + NADP+
cyclohex-2-en-1-one + NADPH
show the reaction diagram
-
isoenzymes 1 and 2
-
r
dehydroepiandrosterone + NADPH
androst-5-ene-3beta,17beta-diol + NADP+
show the reaction diagram
-
-
-
r
dehydroepiandrosterone + NADPH
androst-5-en-3beta,17beta-diol + NADP+
show the reaction diagram
-
-
-
-
?
epiandrosterone + NADPH
androstane-3beta,17beta-diol + NADP+
show the reaction diagram
-
-
-
-
?
pyridine-4-aldehyde + NADPH
pyridine-4-alcohol + NADP+
show the reaction diagram
-
isoenzymes 1 and 2
-
r
testosterone + NAD+
androst-4-ene-3,17-dione + NADH + H+
show the reaction diagram
-
-
-
-
-
testosterone + NAD+
androst-4-ene-3,17-dione + NADH + H+
show the reaction diagram
-
NADP+ is preferred
-
r
testosterone + NAD+
androstenedione + NADH
show the reaction diagram
-
NAD+ shows 20% of the activity with NADP+
-
-
ir
testosterone + NAD+
androstenedione + NADH
show the reaction diagram
-
NAD+ shows ess than 10% of the activity with NADP+
-
-
ir
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
rate of oxidation is less than 30% of those for reduction
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
17beta-hydroxysteroid dehydrogenase 3, reduction of androst-4-ene-3,17-dione is preferred
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
17beta-hydroxysteroid dehydrogenase 3, reduction of androst-4-ene-3,17-dione is preferred
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
17beta-hydroxysterod dehydrogenase 3, reduction of androst-4-ene-3,17-dione is preferred
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
17beta-hydroxysterod dehydrogenase 3, reduction of androst-4-ene-3,17-dione is preferred
-
r
indan-1-ol + NADP+
indan-1-one + NADPH
show the reaction diagram
-
isoenzymes 1 and 2
-
r
additional information
?
-
-
human 17beta-hydroxysteroid dehydrogenases are multifunctional enzymes, isozyme 17beta-HSD4 also performs beta-oxidation of branched fatty acids, like pristanic acid, and in bile acid synthesis, e.g. of di- and trihydroxycholestanoic acids, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
r
5beta-androstane-3alpha,17beta-diol + NADP+
5beta-androstane-3alpha-ol-17-one + NADPH
show the reaction diagram
-
-
-
r
androst-4-ene-3,17-dione + NADPH
testosterone + NADP+
show the reaction diagram
-
the enzyme plays a central role in the development of the male phenotype. Mutations that inactivate the enzyme give rise to a rare form of male pseudohermaphroditism, referred to as 17beta-HSD-3 deficiency
-
-
?
androst-4-ene-3,17-dione + NADPH
testosterone + NADP+
show the reaction diagram
-
convertion of the weak androgen androstendione into the potent androgen testosterone
-
-
?
androstenedione + NADPH + H+
testosterone + NADP+
show the reaction diagram
-
-
-
-
?
androstenedione + NADPH + H+
testosterone + NADP+
show the reaction diagram
-
the enzyme is involved in biosynthesis of testosterone
-
-
?
androstenedione + NADPH + H+
testosterone + NADP+
show the reaction diagram
-
the two reactions 11beta-HSD1-dehydrogenase, EC 1.1.1.146, and 17beta-HSD3, EC 1.1.1.64, which utilize NADPH are competing for NADPH from the same cofactor pool. 11beta-HSD1-dehydrogenase serves as a NADPH-regenerating system that is tightly coupled in regulating 17beta-HSD3 reaction synthesizing testosterone. A cycle can exist whereby the NADPH produced by 11beta-HSD1 dehydrogenase can drive the reductase activity of 17beta-HSD3 and the NADP+ produced by 17beta-HSD3 and other enzymes involved in testosterone biosynthesis can drive the dehydrogenase activity of 11beta-HSD1
i.e. 4-androsten-17beta-ol-3-one
-
?
testosterone + NAD+
androst-4-ene-3,17-dione + NADH + H+
show the reaction diagram
-
NADP+ is preferred
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
17beta-hydroxysterod dehydrogenase 3, reduction of androst-4-ene-3,17-dione is preferred
-
r
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
17beta-hydroxysterod dehydrogenase 3, reduction of androst-4-ene-3,17-dione is preferred
-
r
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
NAD+
-
isoenzyme 1, 40% of its NADP+ dependent activity, isoenzyme 2, less than 5% of its NADP+ dependent activity
NAD+
-
less than 30% activity compared to NADP+
NAD+
-
less than 10% of the activity with NADP+, cosubstrate: testosterone
NAD+
-
20% of the activity with NADP+, cosubstrate: testosterone
NADPH
-
no activity with NADH
NADPH
-
no activity with NADH
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(2E)-3-(4-bromophenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
-
93.3% inhibition at 0.1 mM
(2E)-3-(4-ethylphenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
-
89.1% inhibition at 0.1 mM
(2E)-3-(4-methylphenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
-
92.7% inhibition at 0.1 mM
(2E)-3-[4-(methylsulfanyl)phenyl]-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
-
93.5% inhibition at 0.1 mM
(3alpha,5alpha)-3-[[trans-2,5-dimethyl-4-[[2-(trifluoromethyl)-phenyl]sulfonyl]piperazin-1-yl]methyl]-3-hydroxyandrostan-17-one
-
strong inhibition of isoform 17beta-HSD3 overexpressed in HEK-293 cells
-
(3R,10S,13S)-3-(Adamantan-1-ylmethyl-butyl-amino)-3-hydroxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-one
-
IC50: 80 nM
(3R,10S,13S)-3-[(2-Cyclopentyl-ethyl)-morpholin-4-yl-amino]-3-hydroxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-one
-
IC50: 74 nM
(3R,5S,8R,9S,10S,13S,14S)-3'-benzyl-10,13-dimethyltetradecahydro-2'H spiro[cyclopenta [alpha] phenanthrene-3,5'-[1,3]-oxazolidine]-2',17(2H)-dione
-
strong inhibition of isoform 17beta-HSD3 overexpressed in HEK-293 cells. 44% inhibition at 0.1 microM in homogenized cells
-
(RS)-3(2,3,3-triphenyl-prop-2-enoxycarbonyl)-3(prop-2-ynyl)pyrrolidine-2,5-dione
-
IC50: 0.0091 mM, reduction of androstenedione
(RS)-3(2,3,3-triphenyl-prop-2-enoxycarbonyl)-3(prop-2-ynyl)pyrrolidine-2,5-dione
-
IC50: 0.00915 mM
(RS)-3(3'-phenylpropoxycarbonyl)-3(prop-2-ynyl)pyrrolidine-2,5-dione
-
IC50: 0.0421 mM
1-(4-hydroxyphenyl)-butan-1-one
-
IC50: 0.08951 mM
1-(4-hydroxyphenyl)-ethanone
-
IC50: 1.70892 mM
1-(4-hydroxyphenyl)-heptan-1-one
-
IC50: 0.0784 mM
1-(4-hydroxyphenyl)-hexan-1-one
-
IC50: 0.01802 mM
1-(4-hydroxyphenyl)-nonan-1-one
-
IC50: 0.00286 mM
1-(4-hydroxyphenyl)-octan-1-one
-
IC50: 0.00652 mM
1-(4-hydroxyphenyl)-pentan-1-one
-
IC50: 0.00497 mM; IC50: 0.06052 mM
1-(4-hydroxyphenyl)-propan-1-one
-
IC50: 0.15056 mM
1-(4-hydroxyphenyl)-undeca-1-one
-
IC50: 0.00755 mM
1-(4-[[(2R)-2-methylpiperidin-1-yl]sulfonyl]phenyl)-1,3-dihydro-2H-pyrrol-2-one
-
IC50 value in HCT-116 cells engineered to over-express AKR1C3 is 11 nM
1-(4-[[(2R,6S)-2,6-dimethylpiperidin-1-yl]sulfonyl]phenyl)pyrrolidin-2-one
-
IC50 value in HCT-116 cells engineered to over-express AKR1C3 is 22 nM
1-[4-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)phenyl]pyrrolidin-2-one
-
IC50 value in HCT-116 cells engineered to over-express AKR1C3 is 24 nM
2,5-diphenyl-p-benzoquinone
-
IC50: 0.0027 mM, reduction of androstenedione
2-(2,4-dioxo-1,3-thiazolidin-5-yl)-N-(2-hydroxyphenyl)acetamide
-
inhibitor is about 1000times more selective for isoform AKR1C3 over AKR1C2, and selectivity is even higher when compared with AKR1C1 and AKR1C4
2-methylcinnamic acid
-
IC50: 0.0064 mM
2-[[(3-hydroxyphenyl)carbonyl]amino]-4,5-dimethoxybenzoic acid
-
-
2-[[(3-hydroxyphenyl)carbonyl]amino]-5-nitrobenzoic acid
-
-
3,4,5-trimethoxycinnamic acid
-
IC50: 0.049 mM
3-((4-nitronaphthalen-1-yl)amino)benzoic acid
-
inhibitor nanomolar potency and selective inhibition of isoform AKR1C3 but also acts as an androgen receptor antagonist. It inhibits 5alpha-dihydrotestosterone stimulated androgen receptor reporter gene activity with an IC50 value of 4.7 microM and produces a concentration dependent reduction in androgen receptor levels in prostate cancer cells
3-(17'-oxo-5'alpha-androstan-3'alpha-oxy)propanoic Acid
-
0.003 mM, 48% inhibition
3-(4-Bromo-2-methyl-benzyl)-7-hydroxy-chroman-4-one
-
IC50: 0.0083 mM, reduction of androstenedione
3-(4-Chloro-2-methyl-benzyl)-7-hydroxy-chroman-4-one
-
IC50: 0.0018 mM, reduction of androstenedione
3-(4-Fluoro-2-methyl-benzyl)-7-hydroxy-chroman-4-one
-
IC50: 0.007 mM, reduction of androstenedione
3-coumaric acid
-
34% inhibition at 0.05 mM
3-cyclohexyl-3-hydroxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-one
-
-
3-cyclohexylmethyl-3-hydroxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-one
-
-
3-cyclohexylpropanoic acid
-
weak inhibition, IC50: 0.1 mM, above
3-hexyl-3-hydroxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-one
-
-
3-hydroxy-10,13-dimethyl-3-octyl-hexadecahydro-cyclopenta[a]phenanthren-17-one
-
-
3-hydroxy-10,13-dimethyl-3-phenethyl-hexadecahydro-cyclopenta[a]phenanthren-17-one
-
-
3-hydroxy-10,13-dimethyl-3-phenyl-hexadecahydro-cyclopenta[a]phenanthren-17-one
-
-
3-phenoxybenzoic acid
-
inhibitor carboxylic acid binds to the oxyanion site, in which the carboxylate group very closely overlays the acetate molecule found in other AKR1C3 structures and forms hydrogen bonds to the enzyme catalytic residues His117 and Tyr55, as well as to a conserved water network located in and near the SP3 subpocket. The 3-phenoxy ring extends into the SP1 subpocket and makes van der Waals contacts with the aromatic residues Phe306, Phe311 and Tyr319 that line the pocket
-
3-trifluoromethylcinnamic acid
-
IC50: 0.043 mM
3-[(4-nitrophenyl)amino]benzoic acid
-
94fold selectivity for the inhibition of isoform AKR1C3 over AKR1C2
3-[[4-(methoxymethyl)phenyl]amino]benzoic acid
-
360fold selectivity for the inhibition of isoform AKR1C3 over AKR1C2
3-[[4-(trifluoromethyl)phenyl]amino]benzoic acid
-
250fold selectivity for the inhibition of isoform AKR1C3 over AKR1C2
3-[[4-(trifluoromethyl)phenyl]amino]benzoic acid
-
in complex with AKR1C3. Compound adopts a similar binding orientation as flufenamic acid, however, its phenylamino ring projects deeper into a subpocket and confers selectivity over the other AKR1C isoforms
3a-phenyl-2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-one
-
inhibitor shows 17fold and 30fold selectivity against isoforms AKR1C2 and AKR1C1, respectively, and much higher selectivity against AKR1C4
3alpha,3beta-O-(1'-oxo-1',3'-propanediyloxy)-5alpha-androstan-17-one
-
0.003 mM, 53% inhibition
3alpha-(2'-hydroxypropanoxy)-5alpha-androstan-17-one
-
0.003 mM, 89% inhibition
3alpha-(3'-bromopropanoxy)-5alpha-androstan-17-one
-
0.003 mM, 93% inhibition
3alpha-(3'-hydroxypropanoxy)-5alpha-androstan-17-one
-
0.003 mM, 86% inhibition
3alpha-(prop-2'-enoxy)-5alpha-androstan-17-one
-
0.003 mM, 95% inhibition
3alpha-ethoxy-3beta-(phenylmethyl)-5alpha-androstan-17-one
-
0.003 mM, 92% inhibition, IC50: 352 nM
3alpha-ethoxy-5alpha-androstan-17-one
-
0.003 mM, 95% inhibition
3alpha-hexanoxy-3beta-(phenylmethyl)-5alpha-androstan-17-one
-
0.003 mM, 28% inhibition
3alpha-hexanoxy-5alpha-androstan-17-one
-
0.003 mM, 92% inhibition
3alpha-hydroxy-3'-phenyl-5alpha-androstan-17-one
-
0.003 mM, 95% inhibition, IC50: 81 nM
3alpha-hydroxy-3beta-(3'-hydroxypropyl)-5alpha-androstan-17-one
-
0.003 mM, 74% inhibition
3alpha-hydroxy-3beta-(prop-2'-enyl)-5alpha-androstan-17-one
-
0.003 mM, 76% inhibition
3alpha-hydroxy-3beta-methyl-5alpha-androstan-17-one
-
0.003 mM, 93% inhibition
3alpha-hydroxy-3beta-octyl-5alpha-androstan-17-one
-
0.003 mM, 92% inhibition, IC50: 147 nM
3alpha-hydroxy-3beta-phenylethyl-5alpha-androstan-17-one
-
0.003 mM, 93% inhibition, IC50: 99 nM
3alpha-hydroxy-3beta-phenylmethyl-5alpha-androstan-17-one
-
0.003 mM, 94% inhibition, IC50: 57 nM
3alpha-hydroxy-3beta-phenylpropyl-5alpha-androstan-17-one
-
0.003 mM, 97% inhibition
3alpha-hydroxy-3beta-propyl-5alpha-androstan-17-one
-
0.003 mM, 94% inhibition, IC50: 67 nM
3alpha-hydroxy-3beta-vinyl-5alpha-androstan-17-one
-
0.003 mM, 94% inhibition
3alpha-methoxy-3beta-(2'-phenylethyl)-5alpha-androstan-17-one
-
0.003 mM, 95% inhibition, IC50: 73 nM
3alpha-methoxy-3beta-(phenylmethyl)-5alpha-androstan-17-one
-
0.003 mM, 93% inhibition, IC50: 154 nM
3alpha-methoxy-5alpha-androstan-17-one
-
0.003 mM, 94% inhibition
3alpha-O-(spirotetrahydrofuran-2-yl)-5alpha-androstan-17-one
-
0.003 mM, 94% inhibition
3alpha-propanoxy-3beta-(phenylmethyl)-5alpha-androstan-17-one
-
0.003 mM, 87% inhibition
3alpha-propanoxy-5alpha-androstan-17-one
-
0.003 mM, 93% inhibition
3b-Methyl-5a-androstan-3a-ol-17-on
-
-
3beta,3alpha-O-(1'-oxo-1',3'-propanediyloxy)-5alpha-androstan-17-one
-
0.003 mM, 93% inhibition
3beta-(2'-cyclohexylethyl)-3alpha-methoxy-5alpha-androstan-17-one
-
0.003 mM, 88% inhibition, IC50: 354 nM
3beta-cyclohexyl-3alpha-hydroxy-5alpha-androstan-17-one
-
0.003 mM, 95% inhibition, IC50: 97 nM
3beta-cyclohexylethyl-3alpha-hydroxy-5alpha-androstan-17-one
-
0.003 mM, 93% inhibition, IC50: 60 nM
3beta-cyclohexylethyl-androsterone
-
IC50: 60 nM
3beta-cyclohexylmethyl-3alpha-hydroxy-5alpha-androstan-17-one
-
0.003 mM, 95% inhibition, IC50: 87 nM
3beta-dodecyl-3alpha-hydroxy-5alpha-androstan-17-one
-
0.003 mM, 77% inhibition
3beta-hydroxy-3alpha-(3'-hydroxypropyl)-5alpha-androstan-17-one
-
0.003 mM, 17% inhibition
3beta-hydroxy-3alpha-(prop-2'-enyl)-5alpha-androstan-17-one
-
0.003 mM, 36% inhibition
3beta-hydroxy-3alpha-methyl-5alpha-androstan-17-one
-
0.003 mM, 16% inhibition
3beta-hydroxy-3alpha-phenyl-5alpha-androstan-17-one
-
0.003 mM, 39% inhibition
3beta-hydroxy-3alpha-phenylmethyl-5alpha-androstan-17-one
-
0.003 mM, 39% inhibition
3beta-hydroxy-3alpha-propyl-5alpha-androstan-17-one
-
0.003 mM, 33% inhibition
3beta-n-butyl-3alpha-hydroxy-5alpha-androstan-17-one
-
0.003 mM, 92% inhibition, IC50: 116 nM
3beta-n-hexyl-3alpha-hydroxy-5alpha-androstan-17-one
-
0.003 mM, 95% inhibition, IC50: 100 nM
3beta-phenylmethyl-androsterone
-
IC50: 57 nM
3beta-propyl-androsterone
-
IC50: 67 nM
3beta-s-butyl-3alpha-hydroxy-5alpha-androstan-17-one
-
0.003 mM, 90% inhibition, IC50: 73 nM
3beta-sec-butyl-androsterone
-
IC50: 73 nM
3beta-tert-butyl-3alpha-hydroxy-5alpha-androstan-17-one
-
0.003 mM, 93% inhibition, IC50: 142 nM
4-estrene-3,17-dione
-
-
4-Methylumbelliferone
-
IC50: 0.0009 mM, reduction of androstenedione
4-Methylumbelliferone
-
IC50: 0.0019 mM
5-(3-bromo-4-hydroxybenzyl)-3-(4-methoxyphenyl)-1,3-thiazol-2-one
-
starting compound for high-throughput screening. IC50 value 570 nM in cell-based assay
-
5-(3-bromo-4-hydroxybenzylidene)-3-(4-fluorophenyl)-2-thioxo-1,3-oxazolidin-4-one
-
strong inhibitory activity on isoform 3beta-HSD3
-
5-(3-bromo-4-hydroxybenzylidene)-3-(4-methoxyphenyl)-2-thioxo-1,3-thiazolidin-4-one
-
compound demonstrates significant selectivity for isoform 17beta-hydroxysteroid dehydrogenase type 3 over the related isoenzymes and nuclear receptors. IC50 value 14 nM in cell-based assay
-
5-(3-bromo-4-hydroxybenzylidene)-3-(4-methylphenyl)-2-thioxo-1,3-oxazolidin-4-one
-
strong inhibitory activity on isoform 3beta-HSD3
-
5-(3-chloro-5-fluoro-4-hydroxybenzylidene)-3-(4-methoxyphenyl)-2-thioxo-1,3-oxazolidin-4-one
-
strong inhibitory activity on isoform 3beta-HSD3
-
5-(3-fluoro-4-hydroxybenzylidene)-3-(4-methoxyphenyl)-2-tioxo-1,3-oxazolidin-4-one
-
strong inhibitory activity on isoform 3beta-HSD3
-
5-Androstene-3,17-dione
-
-
5-bromo-2-[[(3-hydroxyphenyl)carbonyl]amino]benzoic acid
-
-
5-chloro-2-[[(3-hydroxyphenyl)carbonyl]amino]benzoic acid
-
-
5-[3,5-dichloro-4-(phosphonoxy)benzylidene]-3-(4-methoxyphenyl)-2-thioxo-1,3-oxazolidin-4-one
-
strong inhibitory activity on isoform 3beta-HSD3
-
5-[3,5-dichloro-4-(phosphonoxy)benzylidene]-3-(4-methoxyphenyl)-2-thioxo-1,3-oxazolidin-4-one
-
strong inhibitory activity on isoform 3beta-HSD3. When administered orally at a high dose of 100 mg/kg, compound shows approximately two times more potent testosterone-lowering effect against a positive control in the luteinizing hormone-releasing hormone-induced T production assay. The T-lowering effect continues at ca 10% level of control over 4 h after administration
-
7-hydroxyflavone
-
IC50: 0.009 mM, reduction of androstenedione
7-hydroxyflavone
-
IC50: 0.06698 mM
atamestane
-
-
baicalein
-
IC50: 0.0093 mM, reduction of androstenedione
baicalein
-
IC50: 0.18592 mM
Biochanin A
-
IC50: 0.0108 mM, reduction of androstenedione
bis(2-butoxyethyl) phthalate
-
potent inhibitor of testis 17beta-hydroxysteroid dehydrogenase type 3, additionally inhibits 3beta-hydroxysteriod dehydrogenase
-
caffeic acid
-
18% inhibition at 0.05 mM
Cinnamic acid
-
IC50: 0.050 mM
clomiphene
-
IC50: 0.0762 mM
coumarin-3-carboxylic acid
-
30% inhibition at 0.05 mM
CuCl2
-
10 mM, 40% inhibition
Cyclopropanecarboxylic acid ((3R,10S,13S)-3-hydroxy-10,13-dimethyl-17-oxo-hexadecahydro-cyclopenta[a]phenanthren-3-yl)-octyl-amide
-
IC50: 57 nM
Cyclopropanecarboxylic acid cyclohexylmethyl-((3R,10S,13S)-3-hydroxy-10,13-dimethyl-17-oxo-hexadecahydro-cyclopenta[a]phenanthren-3-yl)-amide
-
IC50: 85 nM
dicyclohexyl phthalate
-
potent inhibitor of testis 17beta-hydroxysteroid dehydrogenase type 3, additionally inhibits 3beta-hydroxysteriod dehydrogenase
FeCl3
-
10 mM, 54% inhibition
N-Adamantan-1-ylmethyl-N-((3R,10S,13S)-3-hydroxy-10,13-dimethyl-17-oxo-hexadecahydro-cyclopenta[a]phenanthren-3-yl)-butyramide
-
IC50: 35-57 nM
p-chloromercuribenzoate
-
10 mM, strong inhibition, 5% residual activity is reversed to 65% activity by either 1 mM glutathione or cysteine
Pb(NO3)2
-
10 mM, 30% inhibition
phenyl-p-benzoquinone
-
IC50: 0.0057 mM, reduction of androstenedione
Sodium amytal
-
10 mM, 25% inhibition
Sodium cyanide
-
10 mM, progressive and marked inhibition
tamoxifen
-
IC50: 0.098 mM, time-dependent and irreversible
testosterone
-
1 mM, 62.8% inhibition of androstendione reduction
umbelliferone
-
IC50: 0.0014 mM, reduction of androstenedione
umbelliferone
-
IC50: 0.0014 mM
ZnCl2
-
10 mM, 90% inhibition
heptanoic acid (1-{1-[(3-hydroxy-10,13-dimethyl-17-oxo-hexadecahydro-cyclopenta[a]phenanthren-3-ylmethyl)-carbamoyl]-2-phenyl-ethylcarbamoyl}-2-phenyl-ethyl)-amide
-
IC50: 227 nM
additional information
-
activity of 17beta-HSD is significantly decreased in metyrapone-induced corticosterone-deficient rat Leydig cells compared to control, whereas simultaneous administration of corticosterone partially prevented this and maintained the activity at near normal levels
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
testosterone
-
0.023 mM, 2.6fold increase in androstenedione reduction
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.077
-
17beta-hydroxy-5alpha-androstane-3-one
-
-
0.0067
-
17beta-hydroxy-5beta-androstane-3-one
-
-
0.053
-
19-nortestosterone
-
-
0.0031
-
4-oxo-2-nonenal
-
pH 7.4, 25C
-
0.023
-
5alpha-androstane-3alpha,17beta-diol
-
-
0.011
-
5beta-Androstane-3alpha,17beta-diol
-
-
0.029
-
5beta-androstane-3beta,17beta-diol
-
-
0.0007
-
androstenedione
-
-
0.001
-
androstenedione
-
-
0.04
-
androstenedione
-
-
0.47
-
benzene dihydrodiol
-
isoenzyme 1
6.7
-
benzene dihydrodiol
-
isoenzyme 2
0.1012
-
NAD+
-
-
0.177
-
NADH
-
-
0.0046
-
NADP+
-
-
0.011
-
NADP+
-
-
0.014
-
NADP+
-
isoenzyme 2
0.025
-
NADP+
-
isoenzyme 1
0.047
-
NADP+
-
-
0.0083
-
NADPH
-
-
0.0108
-
NADPH
-
-
0.011
-
NADPH
-
-
0.0015
-
testosterone
-
enzyme activity in cell-free homogenate, approximate value
0.027
-
testosterone
-
-
0.0596
-
testosterone
-
enzyme activity in microsomal fraction after centrifugation
0.27
-
testosterone
-
-
0.0033
-
estrone
-
-
additional information
-
additional information
-
the KM-values for R80 mutant enzymes are higher than the Km-value of the wild-type enzyme: for R80K 3.5fold, for R80L 21.6fold, for R80M 90.7fold, for R80Q 61.5fold, for R80Y 61.5fold, for R80Y 85.1fold, for R80I 80fold
-
additional information
-
additional information
-
-
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.148
-
4-oxo-2-nonenal
-
pH 7.4, 25C
-
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
47.8
-
4-oxo-2-nonenal
-
pH 7.4, 25C
0
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.000107
-
2-(2,4-dioxo-1,3-thiazolidin-5-yl)-N-(2-hydroxyphenyl)acetamide
-
pH 7.0, temperature not specified in the publication
0.00273
-
3a-phenyl-2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-one
-
pH 7.0, temperature not specified in the publication
0.0024
-
4-estrene-3,17-dione
-
-
0.0068
-
5-Androstene-3,17-dione
-
-
0.017
-
bis(2-butoxyethyl) phthalate
-
isoform 17beta-hydroxysteroid dehydrogenase type 3 , pH 7.4, 37C
-
0.0285
-
bis(2-butoxyethyl) phthalate
-
isoform 17beta-hydroxysteroid dehydrogenase type 3 , pH 7.4, 37C
-
0.0335
-
bis(2-butoxyethyl) phthalate
-
isoform 3beta-hydroxysteriod dehydrogenase , pH 7.4, 37C
-
0.05
-
bis(2-butoxyethyl) phthalate
-
isoform 3beta-hydroxysteriod dehydrogenase , pH 7.4, 37C
-
0.0055
-
dicyclohexyl phthalate
-
isoform 17beta-hydroxysteroid dehydrogenase type 3, pH 7.4, 37C
0.0085
-
dicyclohexyl phthalate
-
isoform 17beta-hydroxysteroid dehydrogenase type 3, pH 7.4, 37C
0.0165
-
dicyclohexyl phthalate
-
isoform 3beta-hydroxysteriod dehydrogenase, pH 7.4, 37C
0.0219
-
dicyclohexyl phthalate
-
isoform 3beta-hydroxysteriod dehydrogenase, pH 7.4, 37C
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00113
-
(+)-gossypol
-
in PBS buffer, pH 7.2
0.01093
-
(+)-gossypol
-
in PBS buffer, pH 7.2
0.00036
-
(-)-gossypol
-
in PBS buffer, pH 7.2
0.00343
-
(-)-gossypol
-
in PBS buffer, pH 7.2
0.0136
-
(2E)-3-(4-bromophenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.0136
-
(2E)-3-(4-ethylphenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.0134
-
(2E)-3-(4-methylphenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.0058
-
(2E)-3-[4-(methylsulfanyl)phenyl]-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
-
pH not specified in the publication, temperature not specified in the publication
6e-06
-
(3alpha,5alpha)-3-[[trans-2,5-dimethyl-4-[[2-(trifluoromethyl)-phenyl]sulfonyl]piperazin-1-yl]methyl]-3-hydroxyandrostan-17-one
-
assay uses homogenized cells, pH not specified in the publication, temperature not specified in the publication
-
8e-05
-
(3R,10S,13S)-3-(Adamantan-1-ylmethyl-butyl-amino)-3-hydroxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-one
-
IC50: 80 nM
7.4e-05
-
(3R,10S,13S)-3-[(2-Cyclopentyl-ethyl)-morpholin-4-yl-amino]-3-hydroxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-one
-
IC50: 74 nM
0.0091
-
(RS)-3(2,3,3-triphenyl-prop-2-enoxycarbonyl)-3(prop-2-ynyl)pyrrolidine-2,5-dione
-
IC50: 0.0091 mM, reduction of androstenedione
0.00915
-
(RS)-3(2,3,3-triphenyl-prop-2-enoxycarbonyl)-3(prop-2-ynyl)pyrrolidine-2,5-dione
-
IC50: 0.00915 mM
0.0421
-
(RS)-3(3'-phenylpropoxycarbonyl)-3(prop-2-ynyl)pyrrolidine-2,5-dione
-
IC50: 0.0421 mM
0.08951
-
1-(4-hydroxyphenyl)-butan-1-one
-
IC50: 0.08951 mM
1.70892
-
1-(4-hydroxyphenyl)-ethanone
-
IC50: 1.70892 mM
0.0784
-
1-(4-hydroxyphenyl)-heptan-1-one
-
IC50: 0.0784 mM
0.01802
-
1-(4-hydroxyphenyl)-hexan-1-one
-
IC50: 0.01802 mM
0.00286
-
1-(4-hydroxyphenyl)-nonan-1-one
-
IC50: 0.00286 mM
0.00652
-
1-(4-hydroxyphenyl)-octan-1-one
-
IC50: 0.00652 mM
0.00497
-
1-(4-hydroxyphenyl)-pentan-1-one
-
IC50: 0.00497 mM
0.06052
-
1-(4-hydroxyphenyl)-pentan-1-one
-
IC50: 0.06052 mM
0.15056
-
1-(4-hydroxyphenyl)-propan-1-one
-
IC50: 0.15056 mM
0.00755
-
1-(4-hydroxyphenyl)-undeca-1-one
-
IC50: 0.00755 mM
9.4e-05
-
1-(4-[[(2R)-2-methylpiperidin-1-yl]sulfonyl]phenyl)-1,3-dihydro-2H-pyrrol-2-one
-
pH not specified in the publication, temperature not specified in the publication
5.6e-05
-
1-(4-[[(2R,6S)-2,6-dimethylpiperidin-1-yl]sulfonyl]phenyl)pyrrolidin-2-one
-
pH not specified in the publication, temperature not specified in the publication
5.2e-05
-
1-[4-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)phenyl]pyrrolidin-2-one
-
pH not specified in the publication, temperature not specified in the publication
0.0027
-
2,5-diphenyl-p-benzoquinone
-
IC50: 0.0027 mM, reduction of androstenedione
0.000213
-
2-(2,4-dioxo-1,3-thiazolidin-5-yl)-N-(2-hydroxyphenyl)acetamide
-
pH 7.0, temperature not specified in the publication
0.0064
-
2-methylcinnamic acid
-
IC50: 0.0064 mM
0.0052
-
2-[[(3-hydroxyphenyl)carbonyl]amino]-4,5-dimethoxybenzoic acid
-
pH 7.0, temperature not specified in the publication
0.00084
-
2-[[(3-hydroxyphenyl)carbonyl]amino]-5-nitrobenzoic acid
-
pH 7.0, temperature not specified in the publication
0.049
-
3,4,5-trimethoxycinnamic acid
-
IC50: 0.049 mM
0.08
-
3-((4-nitronaphthalen-1-yl)amino)benzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.0083
-
3-(4-Bromo-2-methyl-benzyl)-7-hydroxy-chroman-4-one
-
IC50: 0.0083 mM, reduction of androstenedione
0.0018
-
3-(4-Chloro-2-methyl-benzyl)-7-hydroxy-chroman-4-one
-
IC50: 0.0018 mM, reduction of androstenedione
0.007
-
3-(4-Fluoro-2-methyl-benzyl)-7-hydroxy-chroman-4-one
-
IC50: 0.007 mM, reduction of androstenedione
0.1
-
3-cyclohexylpropanoic acid
-
weak inhibition, IC50: 0.1 mM, above
0.043
-
3-trifluoromethylcinnamic acid
-
IC50: 0.043 mM
3.6e-05
-
3-[(4-nitrophenyl)amino]benzoic acid
-
pH not specified in the publication, temperature not specified in the publication
5.4e-05
-
3-[[4-(methoxymethyl)phenyl]amino]benzoic acid
-
pH not specified in the publication, temperature not specified in the publication
6.2e-05
-
3-[[4-(trifluoromethyl)phenyl]amino]benzoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.00546
-
3a-phenyl-2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-one
-
pH 7.0, temperature not specified in the publication
0.000352
-
3alpha-ethoxy-3beta-(phenylmethyl)-5alpha-androstan-17-one
-
0.003 mM, 92% inhibition, IC50: 352 nM
8.1e-05
-
3alpha-hydroxy-3'-phenyl-5alpha-androstan-17-one
-
0.003 mM, 95% inhibition, IC50: 81 nM
0.000147
-
3alpha-hydroxy-3beta-octyl-5alpha-androstan-17-one
-
0.003 mM, 92% inhibition, IC50: 147 nM
9.9e-05
-
3alpha-hydroxy-3beta-phenylethyl-5alpha-androstan-17-one
-
0.003 mM, 93% inhibition, IC50: 99 nM
5.7e-05
-
3alpha-hydroxy-3beta-phenylmethyl-5alpha-androstan-17-one
-
0.003 mM, 94% inhibition, IC50: 57 nM
6.7e-05
-
3alpha-hydroxy-3beta-propyl-5alpha-androstan-17-one
-
0.003 mM, 94% inhibition, IC50: 67 nM
7.3e-05
-
3alpha-methoxy-3beta-(2'-phenylethyl)-5alpha-androstan-17-one
-
0.003 mM, 95% inhibition, IC50: 73 nM
0.000154
-
3alpha-methoxy-3beta-(phenylmethyl)-5alpha-androstan-17-one
-
0.003 mM, 93% inhibition, IC50: 154 nM
0.000354
-
3beta-(2'-cyclohexylethyl)-3alpha-methoxy-5alpha-androstan-17-one
-
0.003 mM, 88% inhibition, IC50: 354 nM
9.7e-05
-
3beta-cyclohexyl-3alpha-hydroxy-5alpha-androstan-17-one
-
0.003 mM, 95% inhibition, IC50: 97 nM
6e-05
-
3beta-cyclohexylethyl-3alpha-hydroxy-5alpha-androstan-17-one
-
0.003 mM, 93% inhibition, IC50: 60 nM
6e-05
-
3beta-cyclohexylethyl-androsterone
-
IC50: 60 nM
8.7e-05
-
3beta-cyclohexylmethyl-3alpha-hydroxy-5alpha-androstan-17-one
-
0.003 mM, 95% inhibition, IC50: 87 nM
0.000116
-
3beta-n-butyl-3alpha-hydroxy-5alpha-androstan-17-one
-
0.003 mM, 92% inhibition, IC50: 116 nM
0.0001
-
3beta-n-hexyl-3alpha-hydroxy-5alpha-androstan-17-one
-
0.003 mM, 95% inhibition, IC50: 100 nM
5.7e-05
-
3beta-phenylmethyl-androsterone
-
IC50: 57 nM
6.7e-05
-
3beta-propyl-androsterone
-
IC50: 67 nM
7.3e-05
-
3beta-s-butyl-3alpha-hydroxy-5alpha-androstan-17-one
-
0.003 mM, 90% inhibition, IC50: 73 nM
7.3e-05
-
3beta-sec-butyl-androsterone
-
IC50: 73 nM
0.000142
-
3beta-tert-butyl-3alpha-hydroxy-5alpha-androstan-17-one
-
0.003 mM, 93% inhibition, IC50: 142 nM
0.0009
-
4-Methylumbelliferone
-
IC50: 0.0009 mM, reduction of androstenedione
0.0019
-
4-Methylumbelliferone
-
IC50: 0.0019 mM
2e-06
-
5-(3-bromo-4-hydroxybenzylidene)-3-(4-fluorophenyl)-2-thioxo-1,3-oxazolidin-4-one, 5-(3-bromo-4-hydroxybenzylidene)-3-(4-methylphenyl)-2-thioxo-1,3-oxazolidin-4-one, 5-(3-chloro-5-fluoro-4-hydroxybenzylidene)-3-(4-methoxyphenyl)-2-thioxo-1,3-oxazolidin-4-one, 5-(3-fluoro-4-hydroxybenzylidene)-3-(4-methoxyphenyl)-2-tioxo-1,3-oxazolidin-4-one
-
cell-based assay, pH not specified in the publication, temperature not specified in the publication
-
0.0019
-
5-bromo-2-[[(3-hydroxyphenyl)carbonyl]amino]benzoic acid
-
pH 7.0, temperature not specified in the publication
0.0022
-
5-chloro-2-[[(3-hydroxyphenyl)carbonyl]amino]benzoic acid
-
pH 7.0, temperature not specified in the publication
1e-06
-
5-[3,5-dichloro-4-(phosphonoxy)benzylidene]-3-(4-methoxyphenyl)-2-thioxo-1,3-oxazolidin-4-one
-
cell-based assay, pH not specified in the publication, temperature not specified in the publication
-
0.009
-
7-hydroxyflavone
-
IC50: 0.009 mM, reduction of androstenedione
0.06698
-
7-hydroxyflavone
-
IC50: 0.06698 mM
0.0093
-
baicalein
-
IC50: 0.0093 mM, reduction of androstenedione
0.18592
-
baicalein
-
IC50: 0.18592 mM
0.0108
-
Biochanin A
-
IC50: 0.0108 mM, reduction of androstenedione
0.0233
-
bis(2-butoxyethyl) phthalate
-
isoform 17beta-hydroxysteroid dehydrogenase type 3 , pH 7.4, 37C
-
0.0302
-
bis(2-butoxyethyl) phthalate
-
isoform 17beta-hydroxysteroid dehydrogenase type 3 , pH 7.4, 37C
-
0.0503
-
bis(2-butoxyethyl) phthalate
-
isoform 3beta-hydroxysteriod dehydrogenase , pH 7.4, 37C
-
0.0825
-
bis(2-butoxyethyl) phthalate
-
isoform 3beta-hydroxysteriod dehydrogenase , pH 7.4, 37C
-
0.05
-
Cinnamic acid
-
IC50: 0.050 mM
0.0762
-
clomiphene
-
IC50: 0.0762 mM
5.7e-05
-
Cyclopropanecarboxylic acid ((3R,10S,13S)-3-hydroxy-10,13-dimethyl-17-oxo-hexadecahydro-cyclopenta[a]phenanthren-3-yl)-octyl-amide
-
IC50: 57 nM
8.5e-05
-
Cyclopropanecarboxylic acid cyclohexylmethyl-((3R,10S,13S)-3-hydroxy-10,13-dimethyl-17-oxo-hexadecahydro-cyclopenta[a]phenanthren-3-yl)-amide
-
IC50: 85 nM
0.0082
-
dicyclohexyl phthalate
-
isoform 17beta-hydroxysteroid dehydrogenase type 3, pH 7.4, 37C
0.0247
-
dicyclohexyl phthalate
-
isoform 3beta-hydroxysteriod dehydrogenase, pH 7.4, 37C
0.0255
-
dicyclohexyl phthalate
-
isoform 3beta-hydroxysteriod dehydrogenase, pH 7.4, 37C
0.09
-
dicyclohexyl phthalate
-
isoform 17beta-hydroxysteroid dehydrogenase type 3, pH 7.4, 37C
0.000227
-
heptanoic acid (1-{1-[(3-hydroxy-10,13-dimethyl-17-oxo-hexadecahydro-cyclopenta[a]phenanthren-3-ylmethyl)-carbamoyl]-2-phenyl-ethylcarbamoyl}-2-phenyl-ethyl)-amide
-
IC50: 227 nM
3.5e-05
5.7e-05
N-Adamantan-1-ylmethyl-N-((3R,10S,13S)-3-hydroxy-10,13-dimethyl-17-oxo-hexadecahydro-cyclopenta[a]phenanthren-3-yl)-butyramide
-
IC50: 35-57 nM
0.0057
-
phenyl-p-benzoquinone
-
IC50: 0.0057 mM, reduction of androstenedione
0.000383
-
STX-2171
-
at 37C
0.000201
-
STX-2622
-
at 37C
0.000441
-
STX-2624
-
at 37C
0.098
-
tamoxifen
-
IC50: 0.098 mM, time-dependent and irreversible
0.0014
-
umbelliferone
-
IC50: 0.0014 mM, reduction of androstenedione
0.0014
-
umbelliferone
-
IC50: 0.0014 mM
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.0033
-
-
enzyme activity in smooth-surfaced microsomes
0.647
-
-
newly discovered isoenzyme
2.316
-
-
classical enzymes
67.7
-
-
-
96.5
-
-
enzyme activity in microsomal fraction after centrifugation
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.8
-
-
addition of testosterone shifts optimal pH to 7.4-7.8
6.1
-
-
reduction of androst-4-ene-3,17-dione
6.5
7.5
-
at 37C
6.5
-
-
assay at
8.5
-
-
at 50C
10
-
-
sharp drop of activity above
10.2
-
-
oxidation of benzene dihydrodiol, isoenzyme 2
10.6
-
-
oxidation of testosterone
10.8
-
-
oxidation of benzene dihydrodiol, isoenzyme 1
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
8.5
10.5
-
-
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
45
-
-
sharp drop of activity above
47
-
-
classical enzyme
50
-
-
newly discovered isoenzyme
50
-
-
in phosphate buffer at pH 7.4
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
predominantly expressed in the zona reticularis
Manually annotated by BRENDA team
-
low activity in both sexes
Manually annotated by BRENDA team
-
during embryogenesis the enzyme is present from the sphere stage until hatching
Manually annotated by BRENDA team
-
uniform, diffuse, and strong expression of isoform AKR1C3 in normal endometrial epithelium but not in endometrial stromal cells. The expression of AKR1C3 is reduced in both hyperplastic and carcinomatous endometrial epithelium
Manually annotated by BRENDA team
-
uniform, diffuse, and strong expression of isoform AKR1C3 in normal endometrial epithelium but not in endometrial stromal cells. The expression of AKR1C3 is reduced in both hyperplastic and carcinomatous endometrial epithelium
Manually annotated by BRENDA team
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
Manually annotated by BRENDA team
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
Manually annotated by BRENDA team
-
strong isoform AKR1C3 immunoreactivity in columnar epithelium but only weak immunoreactivity in squamous epithelium of the gastrointestinal junction
Manually annotated by BRENDA team
-
expression in male, hardly detectable in female
Manually annotated by BRENDA team
-
expression in male, hardly detectable in female
Manually annotated by BRENDA team
-
expression in male, hardly detectable in female
Manually annotated by BRENDA team
-
isozyme 17beta-HSD4
Manually annotated by BRENDA team
-
strong isoform AKR1C3 immunoreactivity in bronchial epithelium but not in bronchial glands or alveolar pneumocytes
Manually annotated by BRENDA team
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
Manually annotated by BRENDA team
-
isozyme 17beta-HSD1
Manually annotated by BRENDA team
-
isozyme 17beta-HSD1
Manually annotated by BRENDA team
-
expression in male, hardly detectable in female
Manually annotated by BRENDA team
-
expression in male, hardly detectable in female
Manually annotated by BRENDA team
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
Manually annotated by BRENDA team
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
Manually annotated by BRENDA team
additional information
-
no isoform AKR1C3 immunoreactivity in bronchial glands or alveolar pneumocytes and small cell carcinoma of the lung, only weak immunoreactivity in squamous epithelium of the gastrointestinal junction
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
isozyme 17beta-HSD1
Manually annotated by BRENDA team
-
isozyme 17beta-HSD4
Manually annotated by BRENDA team
additional information
-
isoform 17beta-HSD3 shows a cytoplasmic orientation and dependence on glucose-6-phosphate dehydrogenase-generated NADPH
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
31000
-
-
newly discovered isoenzyme, disc electrophoresis
34000
-
-
disc gel electrophoresis
35500
-
-
gel filtration
35500
-
-
-
36500
-
-
SDS-PAGE
36500
-
-
-
39000
-
-
newly discovered isoenzyme, gel filtration
180000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
monomer
-
1 * 35400, sucrose density gradient centrifugation
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
10 ns molecular dynamics simulations of inhibitor bound to isofrom AKR1C3. Binding could induce conformational changes to both inhibitor and enzyme. The compound presumably assumes a stable, energetically favored, planar conformation
-
docking of inhibitors (2E)-3-(4-methylphenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid, (2E)-3-(4-ethylphenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid, (2E)-3-(4-bromophenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid and (2E)-3-[4-(methylsulfanyl)phenyl]-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid to crystal structure. Compounds occupy a similar position of the active site as the co-crystallized indomethacin, with the Aryl1 overlapping with the p-chlorobenzoyl moiety of the indomethacin and the Aryl2 overlapping with an indole part of the indomethacin
-
in complex with 3-phenoxybenzoic acid, to 1.68 A resolution, space group P212121
-
in complex with inhibitor 1-(4-[[(2R)-2-methylpiperidin-1-yl]sulfonyl]phenyl)-1,3-dihydro-2H-pyrrol-2-one. The 2-pyrrolidinone does not interact directly with residues in the oxyanion hole
-
in complex with inhibitor 3-[[4-(trifluoromethyl)phenyl]amino]benzoic acid. Compound adopts a similar binding orientation as flufenamic acid, however, its phenylamino ring projects deeper into a subpocket and confers selectivity over the other AKR1C isoforms
-
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
57
-
-
complete inactivation after 15 min
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
very labile enzyme, loss of activity after storage for 2 weeks at -50C
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
0-4C, 100 mM sodium phosphate, pH 8.0, 0.05% 2-mercaptoethanol, 1 month, loss of 70% activity
-
-20C, 6 months, no loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ammonium sulfate, calcium phosphate gel, starch electrophoresis
-
ammonium sulfate, Sephadex G-100, Sephadex G-75, DEAE-cellulose, hydroxyapatite, newly discovered isoenzyme and classical enzyme
-
affinity chromatography on estrone-aminocaproate-Sepharose
-
ammonium sulfate, DEAE-cellulose, Sephadex G-100, CM-Sephadex, hydroxyapatite
-
ammonium sulfate, Sephadex G-100, DEAE-cellulose, Bio-Gel P-100
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
17beta-hydroxysteroid dehydrogenase 3, expressed in human embryonic kidney 293 cells
-
expressed in LNCaP cells and in an 293-EBNA-based cell line
-
expression in Escherichia coli
-
expression in HEK-293 cell
-
expression in HeLa cell
-
expression of AKR1C3 in Eschericha coli
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
the expression of isoform AKR1C3 is reduced in both hyperplastic and carcinomatous endometrial epithelium
-
exposure of HCT-15 cells to cisplatin results in aquisition of cisplatin resistance and concomitant induction of isoform AKR1C3 and aldo-keto reductase AKR1C1 expression
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
A203V
-
inactive enzyme
E215D
-
inactive enzyme
F208I
-
inactive enzyme
M235V
-
inactive enzyme
P282L
-
inactive enzyme
R80I
-
mutant enzyme shows negligible conversion of androst-4-ene-3,17-dione to testosterone. The Km-value for androstenedione is 80fold higher than the KM-value for the wild-type enzyme
R80K
-
conversion of androst-4-ene-3,17-dione to testosterone is reduced as compared to wild-type enzyme. The Km-value for androstenedione is 3.5fold higher than the KM-value for the wild-type enzyme
R80L
-
conversion of androst-4-ene-3,17-dione to testosterone is strongly reduced as compared to wild-type enzyme. The Km-value for androstenedione is 21.6fold higher than the KM-value for the wild-type enzyme
R80M
-
mutant enzyme shows negligible conversion of androst-4-ene-3,17-dione to testosterone. The Km-value for androstenedione is 90.7fold higher than the KM-value for the wild-type enzyme
R80Q
-
20% residual activity
R80Q
-
-
R80Q
-
mutant enzyme shows negligible conversion of androst-4-ene-3,17-dione to testosterone. The Km-value for androstenedione is 61.5fold higher than the KM-value for the wild-type enzyme
R80Y
-
mutant enzyme shows negligible conversion of androst-4-ene-3,17-dione to testosterone. The Km-value for androstenedione is 85.1fold higher than the KM-value for the wild-type enzyme
S232L
-
inactive enzyme
S65L
-
inactive enzyme
V205E
-
inactive enzyme
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
exposure of HCT-15 cells to cisplatin results in aquisition of cisplatin resistance and concomitant induction of isoform AKR1C3 and aldo-keto reductase AKR1C1 expression. The resistance lowers the sensitivity toward cellular damages evoked by oxidative stress-derived aldehydes, 4-hydroxy-2-nonenal and 4-oxo-2-nonenal that are detoxified by AKR1C1 and AKR1C3. Overexpression of AKR1C1 or AKR1C3 in the parental HCT15 cells mitigates the cytotoxicity of the aldehydes and cisplatin. Knockdown of both AKR1C1 and AKR1C3 in the resistant cells or treatment of the cells with specific inhibitors of the aldo-keto reductases increases the sensitivity to ciplatin toxicity. Pretreatment of the resistant cells with proteasome inhibitor Z-Leu-Leu-Leu-al augments the cisplatin sensitization elicited by aldo-keto reductase inhibitors
medicine
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uniform, diffuse, and strong expression of isoform AKR1C3 in normal endometrial epithelium but not in endometrial stromal cells. The expression of AKR1C3 is reduced in both hyperplastic and carcinomatous endometrial epithelium
medicine
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positive isoform AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction. Isoform AKR1C3 immunoreactivity is absent in small cell carcinoma of the lung