Information on EC 1.1.1.239 - 3alpha(17beta)-hydroxysteroid dehydrogenase (NAD+)

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota

EC NUMBER
COMMENTARY hide
1.1.1.239
-
RECOMMENDED NAME
GeneOntology No.
3alpha(17beta)-hydroxysteroid dehydrogenase (NAD+)
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
testosterone + NAD+ = androstenedione + NADH + H+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
androgen and estrogen metabolism
-
-
Steroid hormone biosynthesis
-
-
Metabolic pathways
-
-
SYSTEMATIC NAME
IUBMB Comments
3alpha(or 17beta)-hydroxysteroid:NAD+ oxidoreductase
Also acts on other 17beta-hydroxysteroids and on the 3alpha-hydroxy group of pregnanes and bile acids. Different from EC 1.1.1.50 3alpha-hydroxysteroid dehydrogenase (Si-specific) or EC 1.1.1.213 3alpha-hydroxysteroid dehydrogenase (Re-specific).
CAS REGISTRY NUMBER
COMMENTARY hide
126469-82-7
-
9028-62-0
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(S)-alpha-tetralol + NADP+
alpha-tetralone + NADPH + H+
show the reaction diagram
-
-
-
-
?
(S)-tetralol + NADP+
? + NADPH
show the reaction diagram
-
-
-
-
?
11alpha-hydroxytestosterone + NAD+
11alpha-hydroxyandrost-4-ene-3,17-dione + NADH
show the reaction diagram
-
156% velocity compared to testosterone
-
r
11beta-hydroxytestosterone + NAD+
11beta-hydroxyandrost-4-ene-3,17-dione + NADH
show the reaction diagram
15alpha-hydroxytestosterone + NAD+
15alpha-hydroxyandrost-4-ene-3,17-dione + NADH
show the reaction diagram
-
131% velocity compared to testosterone
-
r
17beta-hydroxy-1alpha-methyl-5alpha-androstan-3-one + NAD+
1alpha-methyl-5alpha-androstane-3,17-dione + NADH
show the reaction diagram
-
192% velocity compared to testosterone
-
r
17beta-hydroxy-5beta-androstan-3-one + NAD+
5beta-androstane-3,17-dione + NADH
show the reaction diagram
-
86% velocity compared to testosterone
-
r
2-[(2-bromoethyl)(2-[[(2-hydroxyethyl)amino]methyl]-4,6-dinitrophenyl)amino]ethyl methanesulfonate + 2 NADH + 2 H+
2-[(2-bromoethyl)[4-(hydroxyamino)-2-[[(2-hydroxyethyl)amino]methyl]-6-nitrophenyl]amino]ethyl methanesulfonate + 2 NAD+ + H2O
show the reaction diagram
-
i.e. PR-104A, phosphate ester prodrug designed to exploit tumor hypoxia
i.e. PR-104H, enzyme acts as nitroreductase for activation of PR-104A
-
-
3beta-hydroxy-5alpha-androstane-17-one + NAD+
5alpha-androstane-3,17-dione + NADH
show the reaction diagram
-
75% velocity compared to testosterone
-
r
4-androstenedione + NADPH + H+
testosterone + NADP+
show the reaction diagram
-
-
-
-
?
4-oxo-2-nonenal + NADPH + H+
4-hydroxy-2-nonenal + NADP+
show the reaction diagram
-
-
-
-
?
5alpha-androstan-3alpha,17beta-diol + NAD+
5alpha-androstan-3alpha-ol-17-one + NADH
show the reaction diagram
-
-
-
?
5alpha-androstane-3alpha,17beta-diol + NAD+
5alpha-androstane-3alpha-ol-17-one + NADH
show the reaction diagram
5alpha-androstane-3beta,17beta-diol + NAD+
5alpha-androstane-3beta-ol-17-one + NADH
show the reaction diagram
5alpha-dihydrotestosterone + NAD+
5alpha-androstane-3,17-dione + NADH
show the reaction diagram
-
133% velocity compared to testosterone
-
r
5alpha-dihydrotestosterone + NAD+
androstandione + NADH
show the reaction diagram
-
-
-
r
5alpha-dihydrotestosterone + NAD+
androstanedione + NADH
show the reaction diagram
5alpha-pregnan-3,21alpha-diol-20-one + NAD+
5alpha-pregnan-21-ol-3,20-dione + NADH
show the reaction diagram
-
-
-
?
5beta-androstan-17beta-ol-3-one + NAD+
5beta-androstan-3,17-dione + NADH
show the reaction diagram
-
-
-
?
5beta-androstan-3alpha,17beta-diol + NAD+
5beta-androstan-3alpha-ol-17-one + NADH
show the reaction diagram
-
-
-
?
5beta-androstane-3alpha,17beta-diol + NAD+
5beta-androstane-3alpha-ol-17-one + NADH
show the reaction diagram
-
57% velocity compared to testosterone
-
r
5beta-dihydrotestosterone + NAD+
androstanedione + NADH
show the reaction diagram
-
50% initial velocity compared to testosterone
-
r
5beta-pregnan-3alpha,21-diol-20-one + NAD+
5beta-pregnan-21-ol-3,20-dione + NADH
show the reaction diagram
-
-
-
?
5beta-pregnan-3alpha-ol-20-one + NAD+
5beta-pregnan-3,20-dione + NADH
show the reaction diagram
-
-
-
?
6beta-hydroxytestosterone + NAD+
6beta-hydroxyandrost-4-ene-3,17-dione + NADH
show the reaction diagram
-
84% velocity compared to testosterone
-
r
androst-4-ene-3beta,17beta-diol + NAD+
androst-4-ene-3beta-ol-17-one + NADH
show the reaction diagram
-
75% velocity compared to testosterone
-
r
androst-4-ene-3beta,17beta-diol + NAD+
androst-4-ene-3beta-ol-17-one + NADH + H+
show the reaction diagram
-
-
-
-
?
androst-5-ene-3beta,17beta-diol + NAD+
androst-5-ene-3beta-ol-17-one + NADH
show the reaction diagram
-
33% velocity compared to testosterone
-
r
androstandiol + NAD+
androsterone + NADH
show the reaction diagram
-
-
-
r
androstanediol + NAD+
androsterone + NADH
show the reaction diagram
-
-
-
r
estradiol + NAD+
estrone + NADH
show the reaction diagram
estrone + NADPH + H+
17beta-estradiol + NADP+
show the reaction diagram
-
-
-
-
?
glycochenodeoxycholic acid + NAD+
7alpha-hydroxy-3-oxo-5-beta-cholanoyl glycine + NADH
show the reaction diagram
-
-
-
?
glycolithocholic acid + NAD+
3-oxo-5beta-cholanoyl glycine + NADH
show the reaction diagram
-
-
-
?
lithocholic acid + NAD+
5beta-cholan-3-one-24-oic acid + NADH
show the reaction diagram
-
-
-
?
progesterone + NADPH + H+
20alpha-hydroxyprogesterone + NADP+
show the reaction diagram
-
-
-
-
?
prostaglandin D2 + NADPH + H+
9alpha,11beta-prostaglandin F2 + NADP+
show the reaction diagram
-
-
-
-
?
testosterone + NAD+
androst-4-ene-3,17-dione + NADH + H+
show the reaction diagram
testosterone + NADP+
androst-4-ene-3,17-dione + NADPH + H+
show the reaction diagram
-
NADP is 3fold less efficient as cofactor
-
r
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
5alpha-dihydrotestosterone + NAD+
androstandione + NADH
show the reaction diagram
-
-
-
r
androst-4-ene-3beta,17beta-diol + NAD+
androst-4-ene-3beta-ol-17-one + NADH + H+
show the reaction diagram
-
-
-
-
?
androstandiol + NAD+
androsterone + NADH
show the reaction diagram
-
-
-
r
testosterone + NAD+
androst-4-ene-3,17-dione + NADH + H+
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADP+
NADPH
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
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
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
17alpha-methyltestosterone
-
competitive inhibition
17beta-estradiol
-
0.175 mM, 25-40% inhibition of testosterone oxidation
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-[[(3-hydroxyphenyl)carbonyl]amino]-4,5-dimethoxybenzoic acid
-
-
2-[[(3-hydroxyphenyl)carbonyl]amino]-5-nitrobenzoic acid
-
-
21-hydroxypregn-4-ene-3,20-dione
-
0.010 mM, 73% inhibition
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-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-[(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
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
3beta-cyclohexylethyl-androsterone
-
potent inhibitor
3beta-n-hexyl-androsterone
-
potent inhibitor
3beta-phenylethyl-androsterone
-
potent inhibitor
5-bromo-2-[[(3-hydroxyphenyl)carbonyl]amino]benzoic acid
-
-
5-chloro-2-[[(3-hydroxyphenyl)carbonyl]amino]benzoic acid
-
-
5alpha-Androstan-3beta-ol-17-one
-
0.005 mM, 55% inhibition
5alpha-pregnan-3beta-ol-20-one
-
0.005 mM, 52% inhibition
5beta-androstan-3,17-dione
-
product inhibition, forward reaction
5beta-androstan-3beta-ol-17-one
-
0.005 mM, 87% inhibition
5beta-dihydrotestosterone
-
product inhibition, reverse reaction
5beta-Pregnan-3beta-ol-20-one
-
0.005 mM, 81% inhibition
7-hydroxyflavone
-
0.007 mM, 50% inhibition, oxidation of androstandiol
abietic acid
-
0.010 mM, 50% inhibition, oxidation of androstandiol
Ag+
-
0.1 mM, complete inhibition
androstendione
-
-
biochain A
-
0.014 mM, 50% inhibition, reduction of androst-4-ene-3,17-dione, 0.008 mM, oxidation of androstanediol
chrysin
-
0.010 mM, 50% inhibition, oxidation of androstandiol
Cibacron blue
-
-
coumestrol
-
0.005 mM, 50% inhibition, reduction of androst-4-ene-3,17-dione, 0.011 mM, 50% inhibition, oxidation of androstanediol
CuCl2
-
1 mM, complete inhibition
dexamethasone
-
0.10 mM, 39% inhibition
Dienstrol
-
0.010 mM, 60% inhibition
FeCl3
-
10 mM, 46% inhibition
Hexoestrol
Hg2+
-
0.1 mM, complete inhibition
indomethacin
-
0.10 mM, 67% inhibition
kaempferol
-
0.008 mM, 50% inhibition, oxidation of androstandiol
Medroxyprogesterone acetate
-
0.010 mM, 22% inhibition
NaCN
-
1 mM, 50% inhibition
naringenin
-
0.010 mM, 50% inhibition, oxidation of androstandiol
p-chloromercuribenzoate
-
0.1 mM, complete inhibition
quercetin
-
0.009 mM, 50% inhibition, reduction of androst-4-ene-3,17-dione, 0.005 mM, oxidation of androstanediol
Sodium amytal
-
10 mM, 25% inhibition
stilboestrol
-
0.010 mM, 61% inhibition
Triton X-100
-
immediate loss of 60-70% activity, remaining activity is stable for 4 days, competitive vs. testosterone, non-competitive vs. NAD+
zearalenone
-
0.004 mM, 50% inhibition, reduction of androst-4-ene-3,17-dione, 0.002 mM, oxidation of androstanediol
ZnCl2
-
10 mM, 10% inhibition
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0064 - 0.021
17beta-estradiol
0.0031
4-oxo-2-nonenal
0.0049
5beta-androstan-17beta-ol-3-one
-
-
0.0066
5beta-androstan-3,17-dione
-
-
0.0048
5beta-Androstan-3alpha,17beta-diol
-
-
0.0038
5beta-pregnan-3,20-dione
-
-
0.0062
5beta-pregnan-3alpha,17beta-diol-20-one
-
-
0.0046
5beta-Pregnan-3alpha-ol-20-one
-
-
0.0016
androst-4-ene-3,17-dione
-
-
0.024
androstendione
-
reduction of androstendione, pH 7.0
0.009
estrone
-
pH 7.0, 37°C
0.0075
glycochenodeoxycholic acid
-
-
0.003
glycolithocholic acid
-
-
0.0005
lithocholic acid
-
-
0.0068 - 0.27
NAD+
0.0016 - 0.033
testosterone
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.148
4-oxo-2-nonenal
Homo sapiens
-
pH 7.4, 25°C
0.45
5alpha-androstan-3alpha,17beta-diol
Mesocricetus auratus
-
-
0.267
5alpha-Pregnan-3alpha,21-diol-20-one
Mesocricetus auratus
-
-
0.367
5beta-androstan-17beta-ol-3-one
Mesocricetus auratus
-
-
0.167
5beta-androstan-3,17-dione
Mesocricetus auratus
-
-
0.85
5beta-Androstan-3alpha,17beta-diol
Mesocricetus auratus
-
-
0.158
5beta-pregnan-3,20-dione
Mesocricetus auratus
-
-
0.367
5beta-Pregnan-3alpha,21-diol-20-one
Mesocricetus auratus
-
-
0.233
5beta-Pregnan-3alpha-ol-20-one
Mesocricetus auratus
-
-
0.0011
estrone
Homo sapiens
-
pH 7.0, 37°C
0.02
glycochenodeoxycholic acid
Mesocricetus auratus
-
-
0.25
glycolithocholic acid
Mesocricetus auratus
-
-
0.05
lithocholic acid
Mesocricetus auratus
-
-
0.417
testosterone
Mesocricetus auratus
-
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
47.8
4-oxo-2-nonenal
Homo sapiens
-
pH 7.4, 25°C
10426
0.127
estrone
Homo sapiens
-
pH 7.0, 37°C
611
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
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
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0136
(2E)-3-(4-bromophenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
0.0134
(2E)-3-(4-methylphenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
Homo sapiens
-
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
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.000094
1-(4-[[(2R)-2-methylpiperidin-1-yl]sulfonyl]phenyl)-1,3-dihydro-2H-pyrrol-2-one
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.000056
1-(4-[[(2R,6S)-2,6-dimethylpiperidin-1-yl]sulfonyl]phenyl)pyrrolidin-2-one
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.000052
1-[4-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)phenyl]pyrrolidin-2-one
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.000213
2-(2,4-dioxo-1,3-thiazolidin-5-yl)-N-(2-hydroxyphenyl)acetamide
Homo sapiens
-
pH 7.0, temperature not specified in the publication
0.0052
2-[[(3-hydroxyphenyl)carbonyl]amino]-4,5-dimethoxybenzoic acid
Homo sapiens
-
pH 7.0, temperature not specified in the publication
0.00084
2-[[(3-hydroxyphenyl)carbonyl]amino]-5-nitrobenzoic acid
Homo sapiens
-
pH 7.0, temperature not specified in the publication
0.08
3-((4-nitronaphthalen-1-yl)amino)benzoic acid
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.000036
3-[(4-nitrophenyl)amino]benzoic acid
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.000054
3-[[4-(methoxymethyl)phenyl]amino]benzoic acid
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.000062
3-[[4-(trifluoromethyl)phenyl]amino]benzoic acid
Homo sapiens
-
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
Homo sapiens
-
pH 7.0, temperature not specified in the publication
0.0019
5-bromo-2-[[(3-hydroxyphenyl)carbonyl]amino]benzoic acid
Homo sapiens
-
pH 7.0, temperature not specified in the publication
0.0022
5-chloro-2-[[(3-hydroxyphenyl)carbonyl]amino]benzoic acid
Homo sapiens
-
pH 7.0, temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.000176
-
enzyme activity in hepatic cytosol
0.00035
-
enzyme activity in hepatic cytosol
0.00044
-
enzyme activity in hepatic cytosol
0.0007
-
enzyme activity in hepatic microsomes
0.00168
-
enzyme activity in hepatic microsomes
0.00283
-
enzyme activity in hepatic microsomes
0.01794
-
enzyme activity in hepatic microsomes
22.3
-
microsomal activitiy
additional information
-
0.046 micromol min/g liver, microsomes, substrate 5alpha-dihydrotestosterone, coenzyme NADP+; 0.086 micromol min/g liver, microsomes, substrate testosterone, coenzyme NADP+; 0.144 micromol min/g liver, microsomes, substrate 5beta-dihydrotestosterone, coenzyme NADP+; 0.1556 micromol min/g liver, microsomes, substrate 5alpha-dihydrotestosterone, coenzyme NAD+; 0.186 micromol min/g liver, microsomes, substrate testosterone, coenzyme NAD+; 0.388 micromol min/g liver, microsomes, substrate 5beta-dihydrotestosterone, coenzyme NAD+
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6
-
reduction of androst-4-ene-3,17-dione
7
-
oxidation of testosterone, equal velocity of oxidation and reduction at pH 6.5
8.3
-
-
8.5 - 9.5
-
-
9 - 10
-
oxidation of testosterone, equal velocity of oxidation and reduction at pH 8.0
9.5
-
solubilized and membrane bound enzyme
9.6
-
sharp drop above
10
-
reduction of androstendione
10.4
-
oxidation of 5beta-androstan-3alpha,17beta-diol
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 10
-
-
6 - 9.5
-
sharp decrease above pH 10.0
8 - 9.6
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30 - 40
-
-
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
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
-
pre- and peri-pubertal changes promote expression of the enzyme in Leydig cells
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
-
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
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in contrast to the normal adult testis, the pediatric cryptorchid testis shows AKR1C3 expression in 18%-26% of Sertoli cells in patients at Tanner stages 2 and beyond
Manually annotated by BRENDA team
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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
PDB
SCOP
CATH
ORGANISM
UNIPROT
Thermosynechococcus elongatus (strain BP-1)
Thermosynechococcus elongatus (strain BP-1)
Thermosynechococcus elongatus (strain BP-1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
59000
-
gel filtration, native PAGE
68000
-
gel filtration
86000
-
native PAGE
130000
-
partly purified enzyme, gel filtration
176000
-
agarose gel chromatography and density gradient centrifugation of Triton X-100 solubilized microsomes
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Crystallization/COMMENTARY
ORGANISM
UNIPROT
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, with an estimated free energy of binding of ?5 kcal/mol
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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
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in complex with 3-phenoxybenzoic acid, to 1.68 A resolution, space group P212121
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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
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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
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
43
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half life of 10 min at pH 10.0, no decrease in activity in the presence of 0.2 mM testosterone, 10% activity lost after 30 min at pH 7.0
50
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20% activity lost after 1 h in the presence of 52.5% glycerol, half-time for heat inactivation 120 min, activity is rapidly lost above 50°C
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
stable at 4°C for at least 10-12 days in the presence of 10 mM 2-mercaptoethanol, activity increases 2fold in the first 2-3 days
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 20 mM potassium phosphate, 50% glycerol, 1 mM dithiotreitol, 1 mM EDTA, pH 7.5, 1 year, no loss in activity
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-80°C, 30 mM Tris-HCl, pH 8.4, 1 mM EDTA, 1 mM dithiothreitol, several months, no loss of activity
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4°C, 10 mM Tris/HCl buffer, pH 8.0, 5 mM 2-mercaptoethanol, 0.5 mM EDTA
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4°C, 50 mM Tris-HCl, pH 9.0, 20% glycerol, 100 mM KCl, 5 mg/ml N-octyl glucoside, 24 h, 20% loss of activity, -20°C, 1 week, no loss of activity
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4°C-6°C, 60 mM sodium diphosphate, pH 9.5, a few days, no loss in activity
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ammonium sulfate, DEAE cellulose, phenyl-Sepharose, Red-agarose
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DEAE-cellulose, gelfiltration, phenyl Sepharose
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recombinant enzyme
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Sephadex G-200, DEAE-cellulose, 9fold purification
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli
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expressed in HeLa human cervical carcinoma cells and COS-1 monkey kidney tumor cells
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expression in Escherichia coli
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expression in MCF-7 cell
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
AKR1C3 expression occurs in a Tanner stage dependent-fashion
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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
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marked upregulation of AKR1C3 is found in a subset including hepatocellular, bladder, renal, gastric, and non-small cell lung carcinoma
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the expression of isoform AKR1C3 is reduced in both hyperplastic and carcinomatous endometrial epithelium
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine