Information on EC 1.1.1.50 - 3alpha-hydroxysteroid 3-dehydrogenase (Si-specific) and Organism(s) Homo sapiens

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Homo sapiens


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


The taxonomic range for the selected organisms is: Homo sapiens

EC NUMBER
COMMENTARY hide
1.1.1.50
-
RECOMMENDED NAME
GeneOntology No.
3alpha-hydroxysteroid 3-dehydrogenase (Si-specific)
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
testosterone and androsterone degradation to androstendione
-
-
Primary bile acid biosynthesis
-
-
Steroid hormone biosynthesis
-
-
Metabolic pathways
-
-
SYSTEMATIC NAME
IUBMB Comments
3alpha-hydroxysteroid:NAD(P)+ 3-oxidoreductase (Si-specific)
The enzyme acts on androsterone and other 3alpha-hydroxysteroids and on 9-, 11- and 15-hydroxyprostaglandin. Si-specific with respect to NAD+ or NADP+. cf. EC 1.1.1.213, 3alpha-hydroxysteroid 3-dehydrogenase (Re-specific).
CAS REGISTRY NUMBER
COMMENTARY hide
9028-56-2
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
human 3alpha-HSD3 shares 97.8% sequence identity with human 20-alpha hydroxysteroid dehydrogenase (20alpha-HSD) and there is only one amino acid difference (residue 54) that is located in their steroid binding pockets. 20alpha-HSD displays a distinctive ability in transforming progesterone to 20alpha-hydroxy-progesterone
malfunction
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
1-acenaphthenol + NADP+
?
show the reaction diagram
-
isozymes AKR1C1-AKR1C4
-
-
r
1-acenaphthenol + NADPH
?
show the reaction diagram
-
-
-
-
?
1-indanol + NADP+
?
show the reaction diagram
-
isozymes AKR1C1-AKR1C4
-
-
r
17beta-estradiol + NADP+
estrone + NADPH
show the reaction diagram
-
-
-
-
r
17beta-hydroxy-dihydrotestosterone + NAD+
5alpha-androstan-3,17-dione + NADH
show the reaction diagram
-
-
-
r
3alpha-adiol + NAD(P)+
dihydrotestosterone + NAD(P)H
show the reaction diagram
-
-
-
r
3alpha-androstanediol + NAD+
5alpha-dihydrotestosterone + NADH
show the reaction diagram
-
oxidation utilizing NAD+ as a cofactor is the preferred reaction in vitro
-
-
r
3alpha-hydroxytibolone + NAD+
tibolone + NADH
show the reaction diagram
-
isozymes AKR1C2 and AKR1C4, no activity with isozyme AKR1C1
-
-
r
3alpha-tetrahydroprogesterone + NADH
5alpha-dihydroprogesterone + NAD+
show the reaction diagram
-
-
-
r
3beta-hydroxytibolone + NAD+
tibolone + NADH
show the reaction diagram
-
isozymes AKR1C2, AKR1C1, and AKR1C4
-
-
r
4-pregnen-3alpha,20beta-diol + NAD+
(20beta)-20-hydroxypregn-4-en-3-one + NADH + H+
show the reaction diagram
-
-
-
?, ir
5alpha-androstan-3alpha,17beta-diol + NAD(P)+
17beta-hydroxy-5alpha-androstan-3-one + NADPH
show the reaction diagram
5alpha-androstan-3alpha,17beta-diol + NAD(P)H
5alpha-dihydrotestosterone + NAD(P)+
show the reaction diagram
5alpha-dihydrocortisol + NADPH
3alpha,5alpha-tetrahydrocortisol + NADP+
show the reaction diagram
-
-
-
?
5alpha-dihydroprogesterone + 2 NADPH + 2 H+
4-pregnen-3alpha,20beta-diol + 2 NADP+
show the reaction diagram
5alpha-dihydroprogesterone + NAD(P)H
4-pregnen-3alpha,20beta-diol + NAD(P)+
show the reaction diagram
-
-
-
-
?
5alpha-dihydroprogesterone + NADPH
(3alpha,5alpha)-3-hydroxypregnan-20-one + NADP+
show the reaction diagram
-
isozymes AKR1C1-AKR1C4
-
-
r
5alpha-dihydroprogesterone + NADPH
4-pregnen-3alpha,20beta-diol + NADP+
show the reaction diagram
5alpha-dihydroprogesterone + NADPH
5alpha-hydroxy-pregnan-20-one + NADP+
show the reaction diagram
-
isozyme AKR1C2
-
-
?
5alpha-dihydroprogesterone + NADPH + H*
3alpha,5alpha-3-hydroxypregnan-20-one + 5alpha,20alpha-tetrahydroprogesterone + NADP+
show the reaction diagram
-
-
-
-
?
5alpha-dihydroprogesterone + NADPH + H+
3alpha,5alpha-3-hydroxypregnan-20-one + NADP+
show the reaction diagram
5alpha-dihydroprogesterone + NADPH + H+
4-pregnen-3alpha,20beta-diol + NADP+
show the reaction diagram
5alpha-dihydrotestosterone + NAD(P)H
3beta-adiol + NAD(P)+
show the reaction diagram
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstan-3alpha,17beta-diol + NAD(P)+
show the reaction diagram
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
show the reaction diagram
5alpha-dihydrotestosterone + NADH
3alpha-androstanediol + NAD+
show the reaction diagram
-
reaction direction is regulated by the NAD+:NADPH relation in the cell
-
-
r
5alpha-dihydrotestosterone + NADPH
3alpha-androstanediol + NADP+
show the reaction diagram
5alpha-dihydrotestosterone + NADPH + H+
5alpha-androstane-3alpha,17beta-diol + NADP+
show the reaction diagram
5alpha-pregnan-3,20-dione + NAD(P)H
3alpha-hydroxy-5alpha-pregnan-20-one + NAD(P)+
show the reaction diagram
-
-
-
?
5beta-androstan-3,17-dione + NAD(P)H
5beta-androstan-17one-3-ol + NAD(P)+
show the reaction diagram
-
-
-
-
r
5beta-androstan-3alpha,17beta-diol + NADP+
17beta-hydroxy-5beta-androstan-3-one + NADPH
show the reaction diagram
-
-
-
-
r
5beta-dihydrocortisol + NADPH
3alpha,5beta-tetrahydrocortisol + NADP+
show the reaction diagram
-
-
-
?
5beta-dihydroprogesterone + NADPH
?
show the reaction diagram
-
isozyme AKR1C1 and AKR1C2
-
-
?
5beta-dihydroprogesterone + NADPH + H+
3alpha,5beta-3-hydroxypregnan-20-one + NADP+
show the reaction diagram
-
preferred substrate
-
-
?
5beta-dihydrotestosterone + NAD(P)H
5beta-androstan-3alpha,17beta-diol + NAD(P)+
show the reaction diagram
-
-
-
-
?
9,10-phenanthrenequinone + NADPH
?
show the reaction diagram
-
-
-
-
?
9-(phenylcarbonyl)-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one + NADPH
9-[hydroxy(phenyl)methyl]-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one + NADP+
show the reaction diagram
androsterone + NAD(P)+
5alpha-androstan-3,17-dione + NAD(P)H
show the reaction diagram
androsterone + NADP+
androstane-3,17-dione + NADPH
show the reaction diagram
benzenedihydrodiol + NADP+
?
show the reaction diagram
-
isozymes AKR1C1-AKR1C4
-
-
r
estradiol + NAD(P)H
estrone + NAD(P)+
show the reaction diagram
-
-
-
?
oxidized 8-acetyl-2,3,5,6-tetrahydro-1H,4H-11-oxa-3a-azabenzo[de]anthracen-10-one + NAD(P)H
reduced 8-acetyl-2,3,5,6-tetrahydro-1H,4H-11-oxa-3a-azabenzo[de]anthracen-10-one + NAD(P)+
show the reaction diagram
-
synthetic compound with fluorophore core
-
-
r
p-nitrobenzaldehyde + NAD(P)H
p-nitrobenzylalcohol + NAD(P)+
show the reaction diagram
-
-
-
-
-
pregn-4-en-3,20-dione + NADPH + H+
3alpha-hydroxypregn-4-en-20-one + NADP+
show the reaction diagram
-
-
-
r
testosterone + NAD(P)+
androstenedione + NAD(P)H + H+
show the reaction diagram
testosterone + NADP+
4-androstene-3,17-dione + NADPH + H+
show the reaction diagram
-
isozymes AKR1C1-AKR1C4
-
-
r
testosterone + NADPH
?
show the reaction diagram
-
-
-
-
?
tibolone + NADPH
3-hydroxytibolone + NADP+
show the reaction diagram
tibolone + NADPH
3alpha-hydroxytibolone + NADP+
show the reaction diagram
-
isozyme AKR1C4 acts predominantly 3alpha-specific, isozyme AKR1C3 performs both 3alpha- and 3beta-reduction, tibolone is [7alpha,17alpha]-17-hydroxy-7-methyl-19-nor-pregn-5(10)-en-20-yn-3-one, or livial, a DELTA5(10)-ene-ketosteroid and a hormone replacement therapeutic used in the treatment of climacteric complaints and the prevention of osteoporosis, binding mode
-
-
r
tibolone + NADPH
3beta-hydroxytibolone + NADP+
show the reaction diagram
-
isozyme AKR1C1 is stereospecific forming exclusively the beta-isomer, isozyme AKR1C2 is 3beta-specific with substrate tibolone, isozyme AKR1C3 performs both 3alpha- and 3 beta-reduction, tibolbone is [7alpha,17alpha]-17-hydroxy-7-methyl-19-nor-pregn-5(10)-en-20-yn-3-one, or livial, a DELTA5(10)-ene-ketosteroid and a hormone replacement therapeutic used in the treatment of climacteric complaints and the prevention of osteoporosis
-
-
r
additional information
?
-
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
4-pregnen-3alpha,20beta-diol + NAD+
(20beta)-20-hydroxypregn-4-en-3-one + NADH + H+
show the reaction diagram
Q04828
-
-
-
ir
5alpha-dihydroprogesterone + 2 NADPH + 2 H+
4-pregnen-3alpha,20beta-diol + 2 NADP+
show the reaction diagram
5alpha-dihydroprogesterone + NAD(P)H
4-pregnen-3alpha,20beta-diol + NAD(P)+
show the reaction diagram
-
-
-
-
?
5alpha-dihydroprogesterone + NADPH
4-pregnen-3alpha,20beta-diol + NADP+
show the reaction diagram
Q04828
-
-
-
?
5alpha-dihydroprogesterone + NADPH + H+
3alpha,5alpha-3-hydroxypregnan-20-one + NADP+
show the reaction diagram
5alpha-dihydroprogesterone + NADPH + H+
4-pregnen-3alpha,20beta-diol + NADP+
show the reaction diagram
-
in the prostate: forward reaction by type 2 isozyme AKR1C3, reverse reaction by type 3 isozyme AKR1C2
-
-
ir
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
show the reaction diagram
5alpha-dihydrotestosterone + NADH
3alpha-androstanediol + NAD+
show the reaction diagram
-
reaction direction is regulated by the NAD+:NADPH relation in the cell
-
-
r
5alpha-dihydrotestosterone + NADPH
3alpha-androstanediol + NADP+
show the reaction diagram
5alpha-dihydrotestosterone + NADPH + H+
5alpha-androstane-3alpha,17beta-diol + NADP+
show the reaction diagram
9-(phenylcarbonyl)-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one + NADPH
9-[hydroxy(phenyl)methyl]-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one + NADP+
show the reaction diagram
-
competitive substrate, fluorometric activity measurement in intact cells, overview
-
-
?
tibolone + NADPH
3-hydroxytibolone + NADP+
show the reaction diagram
-
tibolone is used to treat climacteric symptoms and prevent osteoporosis, it exerts tissue-selective effects via site-specific metabolism into 3alpha- and 3beta-hydroxymetabolites and a DELTA4-isomer
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NAD(P)+
-
-
NAD(P)H
-
-
NADP+
NADPH
additional information
-
cytosolic and microsomal enzymes have different cofactor preferences: cytosolic enzymes prefer NADP+/NADPH, microsomal prefer NAD+/NADH
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
9-(phenylcarbonyl)-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one
-
competitive
bromazepam
-
competitive inhibition of isozymes AKR1C1, AKR1C4, and AKR1C2
celecoxib
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.050 mM in fluorometric assay, in vitro IC50: 0.050 mM in fluorometric assay
cloxazolam
-
potent and specific, competitive inhibition of isozymes AKR1C1, AKR1C4, and AKR1C2
dexamethasone
-
-
dexamethasone 21-acetate
-
-
dexamethasone 21-hemisuccinate
-
-
diazepam
-
competitive inhibition of isozymes AKR1C1, AKR1C4, and AKR1C2
estazolam
-
competitive inhibition of isozymes AKR1C1, AKR1C4, and AKR1C2
Flufenamic acid
flunitrazepam
-
competitive inhibition of isozymes AKR1C1 and AKR1C2
fluoxetine
-
allosteric interaction
Ibuprofen
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.017 mM in fluorometric assay, in vitro IC50: 0.009 mM in fluorometric assay
medazepam
-
competitive inhibition of isozymes AKR1C1, AKR1C4, and AKR1C2
NADPH
naproxen
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.0094 mM in fluorometric assay, 0.016 mM in radiometric assay, in vitro IC50: 0.0027 mM in fluorometric assay
nitrazepam
-
competitive inhibition of isozymes AKR1C1, AKR1C4, and AKR1C2
Phenolphthalein
-
AKR1C4-selective inhibitor, in vitro and in vivo inhibition, IC50: 0.0004 mM
testosterone
-
at concentration 0.001 mM 75% inhibition
tibolone
-
strong substrate inhibition of isozyme AKR1C2
ursodeoxycholate
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
fluoxetine
-
activates allopregnanolone formation in vivo, not in vitro at a concentration up to 0.05 mM, therefore in vivo activation is probably not realized by enzyme activation but a different mechanism
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.017 - 0.042
(2Z)-2-(5-hydroxy-4,6-dimethyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-N,N-di(prop-2-en-1-yl)hydrazinecarbothioamide
0.022 - 0.14
1-Acenaphthenol
0.048 - 1.4
1-Indanol
0.0031
3alpha-androstanediol
-
pH 7.0, 25°C, recombinant enzyme
0.005
3alpha-tetrahydroprogesterone
-
-
0.087
4-Nitrobenzaldehyde
-
NADPH, detection spectrophotometrically
0.0006 - 0.026
5alpha-dihydroprogesterone
0.0001 - 0.07103
5alpha-dihydrotestosterone
0.018
5beta-Dihydrocortisol
-
-
0.00051 - 0.0012
5beta-dihydroprogesterone
0.021
9,10-phenanthrenequinone
-
NADPH, detection spectrophotometrically
0.003
9-(phenylcarbonyl)-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one
-
recombinant enzyme in intact COS-1 cells
0.0015
allopregnanolone
-
pH 7.0, 25°C
0.004
androstanedione
-
NADPH, detection spectrophotometrically
0.0001 - 0.048
androsterone
0.017 - 1.8
benzenedihydrodiol
0.00023
NADP+
-
pH 7.0, 25°C
0.00007
NADPH
-
pH 7.0, 25°C
0.0025
oxidized 8-acetyl-2,3,5,6-tetrahydro-1H,4H-11-oxa-3a-azabenzo[de]anthracen-10-one
-
isozyme AKR1C3
0.00084 - 0.00213
pregn-4-en-3,20-dione
0.012
testosterone
-
NADP+, detection radiometrically
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.004 - 0.507
(2Z)-2-(5-hydroxy-4,6-dimethyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-N,N-di(prop-2-en-1-yl)hydrazinecarbothioamide
0.13 - 0.59
1-Acenaphthenol
0.09 - 0.21
1-Indanol
0.183
3alpha-adiol
-
-
-
0.008
3alpha-androstanediol
-
pH 7.0, 25°C, recombinant enzyme
0.000016 - 0.012
3alpha-hydroxytibolone
0.000016 - 0.016
3beta-hydroxytibolone
1.08
4-Nitrobenzaldehyde
-
-
0.0023 - 0.0735
4-pregnen-3alpha,20beta-diol
0.003 - 0.04
5alpha-dihydroprogesterone
0.0038 - 0.1153
5alpha-dihydrotestosterone
0.0167 - 0.05
5beta-dihydroprogesterone
18.9
9,10-phenanthrenequinone
-
-
0.00017
allopregnanolone
-
pH 7.0, 25°C
1.9
androstanedione
-
detection spectrophotometrically
0.0018 - 0.133
androsterone
0.015 - 0.05
benzenedihydrodiol
0.00017
NADP+
-
pH 7.0, 25°C
0.003
NADPH
-
pH 7.0, 25°C
0.14
oxidized 8-acetyl-2,3,5,6-tetrahydro-1H,4H-11-oxa-3a-azabenzo[de]anthracen-10-one
-
isozyme AKR1C3
0.0035 - 0.0392
pregn-4-en-3,20-dione
0.0167
stanolone
-
-
0.0757
testosterone
-
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.623 - 28.07
5alpha-dihydrotestosterone
4.167 - 18.4
pregn-4-en-3,20-dione
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0003 - 0.0029
diazepam
0.0008 - 0.001
estazolam
0.0011 - 0.0086
medazepam
0.011 - 0.027
nitrazepam
0.000027 - 0.00055
ursodeoxycholate
additional information
additional information
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.05
celecoxib
Homo sapiens
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.050 mM in fluorometric assay, in vitro IC50: 0.050 mM in fluorometric assay
0.00031 - 1.084
Flufenamic acid
0.009
Ibuprofen
Homo sapiens
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.017 mM in fluorometric assay, in vitro IC50: 0.009 mM in fluorometric assay
0.0027
naproxen
Homo sapiens
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.0094 mM in fluorometric assay, 0.016 mM in radiometric assay, in vitro IC50: 0.0027 mM in fluorometric assay
0.0004
Phenolphthalein
Homo sapiens
-
AKR1C4-selective inhibitor, in vitro and in vivo inhibition, IC50: 0.0004 mM
0.000049
ursodeoxycholate
Homo sapiens
-
natural inhibitor, in vivo IC50: 0.00024 mM in fluorometric assay, 0.00014 mM in radiometric assay, in vitro IC50: 0.000049 mM in fluorometric assay
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00002
-
purified recombinant isozymes AKR1C1 and AKR1C3, substrate 3alpha-hydroxytibolone
0.00015
-
purified recombinant isozyme AKR1C3, substrate 3beta-hydroxytibolone
0.0005
-
substrate androsterone with cofactor NADP+, detection radiometrically
0.00079
-
purified recombinant isozyme AKR1C1, substrate 3beta-hydroxytibolone
0.0013
-
substrate 5alpha-dihydrotestosterone with cofactor NADP+, detection radiometrically
0.0025
-
substrate 5alpha-dihydrotestosterone with cofactor NADPH, detection spectrophotometrically
0.0037
-
purified recombinant isozyme AKR1C3, substrate 4-pregnen-3alpha,20beta-diol
0.0039
-
purified recombinant isozyme AKR1C1, substrate 4-pregnen-3alpha,20beta-diol
0.0042
-
substrate 5alpha-dihydrotestosterone with cofactor NADPH, detection radiometrically
0.0048
-
substrate 3alpha-androstanediol with cofactor NADP+, detection spectrophotometrically
0.00653
-
purified recombinant isozyme AKR1C4, substrate 3beta-hydroxytibolone
0.0085
-
substrate 3alpha-androstanediol with cofactor NADP+, detection radiometrically
0.011
-
-
0.0111
-
substrate androstanedione with cofactor NADPH, detection spectrophotometrically
0.0134
-
substrate 3alpha-androstanediol with cofactor NADP+, detection fluorometrically
0.0135
-
-
0.0188
-
purified recombinant isozyme AKR1C4, substrate 3alpha-hydroxytibolone
0.0253
-
purified recombinant isozyme AKR1C2, substrate 3beta-hydroxytibolone
0.031
-
substrate dihydrotestosterone
0.119
-
purified recombinant isozyme AKR1C4, substrate 4-pregnen-3alpha,20beta-diol
0.13
-
substrate 4-nitrobenzaldehyde with cofactor NADPH, detection spectrophotometrically
0.538
-
substrate 9,10-phenanthrenequinone with cofactor NADPH, detection spectrophotometrically
76.1
-
purified recombinant isozyme AKR1C2, substrate 4-pregnen-3alpha,20beta-diol
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.8 - 7.4
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
the urothelial epithelium lining the renal pelvis is strongly immunoreactive, but stromal cells in the underlying supporting connective tissue are negative
Manually annotated by BRENDA team
-
only a small number of epithelial cells are immunoreactive with both nuclear and cytoplasmic reactivity
Manually annotated by BRENDA team
-
primary, high expression and activity in healthy hepatocytes
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
isozyme AKR1C3
Manually annotated by BRENDA team
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in Leydig cells, but no or poor activity in germ cells and Sertoli cells
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37000
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gel filtration
43000
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x * 43000, 3alpha-hydroxysteroid dehydrogenase, x * 65000, 3alpha-hydroxysteroid dehydrogenase-Del1 deposition domain fusion protein, SDS-PAGE
65000
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x * 43000, 3alpha-hydroxysteroid dehydrogenase, x * 65000, 3alpha-hydroxysteroid dehydrogenase-Del1 deposition domain fusion protein, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
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x * 43000, 3alpha-hydroxysteroid dehydrogenase, x * 65000, 3alpha-hydroxysteroid dehydrogenase-Del1 deposition domain fusion protein, SDS-PAGE
monomer
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1 * 37000, SDS-PAGE
additional information
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isozyme AKR1C2 shows an (alphabeta)8-barrel structure
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
3alpha-HSD3-NADP+-progesterone complex and 3alpha-HSD3 mutant V54L-NADP+-progesterone complex, sitting drop vapor diffusion method, room temperature, the reservoir solution contains 100 mM sodium cacodylate, pH 6.0, 200 mM ammonium sulfate, 24-26% w/v PEG 3350, with 0.8 mM progesterone, 3-14 days, X-ray diffraction structure determination and analysis at 2.0-2.2 A resolution, molecular replacement with search model, PDB ID 1J96. Progesterone adopts two different binding modes to form complexes within the wild-type enzyme, with one binding mode similar to the orientation of a bile acid (ursodeoxycholate) in the reported ternary complex of human 3alpha-HSD3-NADP+-ursodeoxycholate and the other binding mode resembling the orientation of 20alpha-OHProg in the ternary complex of human 20alpha-HSD-NADP+-20alpha-OHProg
alpha/beta-barrel, NADP+ is bound in an extended conformation, type III isoform
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crystal structure of human 3alpha-HSD3-NADP(+)/5alpha-androstane-3,17-dione/epiandrosterone complex obtained by co-crystallization with 5alpha-androstane-3,17-dione (5alpha-DHT) in the presence of NADP+. Although 5alpha-DHT is introduced during the crystallization, oxidoreduction of 5alpha-DHT occurs. The locations of 5alpha-androstane-3,17-dione and epiandrosterone are identified in the steroid-binding sites of two 3alpha-HSD3 molecules per crystal asymmetric unit. An overlay shows that 5alpha-androstane-3,17-dione and epiandrosterone are oriented upside-down and flipped relative to each other, providing structural clues for 5alpha-DHT reverse binding in the enzyme with the generation of different products
isozyme AKR1C2 in ternary complex with NADP+ and ursodeoxycholate, X-ray diffraction structure determination and analysis at 3.0 A resolution, molecular replacement
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recombinant type 3 isozyme AKR1C2 in complex with NADP+ and ursodeoxycholate, X-ray structure determination and analysis at 3.0 A resolution
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type III isoform
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
stable in phosphate 50 mM plus 10-20% glycerol at 4°C, while freezing and thawing results in a great loss of enzyme activity
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme from Escherichia coli strain C41(DE3) in a successive chromatographic procedure, to homogeneity
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recombinant enzymes from Escherichia coli by DE52 and Blue Sepharose chromatography
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recombinant from Escherichia coli
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recombinant GST-fusion protein from Escherichia coli by affinity chromatography on a glutathione resin, cleavage of the GST-tag by thrombin
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recombinant GST-tagged enzyme from Escherichia coli strain BL21(DE3)pLysS by glutathione affinity chromatography, cleavage of the tag by thrombin, and anion exchange chromatography
recombinant isozymes AKR1C1-AKR1C4 from Escherichia coli by DE52 ion exchange and Blue Sepharose chromatography, to homogeneity
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
co-expression of the enzyme with the LXR alpha receptor in HuH7 and HepG2 cells; expressed in Hu-H7 cells and Hep-G2 cells
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expression in baculovirus system with Sf9 cells
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expression in Cos-1 cells
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expression in Escherichia coli
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expression of isozyme AKR1C2 in Escherichia coli
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expression of isozymes AKR1C1-4 in Escherichia coli
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expression of type II isoform in Escherichia coli
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from human cDNA library, expression as GST-fusion protein in Escherichia coli strain BL21(DE3)
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isozymes AKR1C1-AKR1C4, genetic organization, transient expression in COS-1 cells
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overexpression in Escherichia coli strain C41(DE3)
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overexpression of GST-tagged enzyme in Escherichia coli strain BL21(DE3)pLysS
overexpression of isozymes AKR1C1-AKR1C4 in Escherichia coli
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overexpression of isozymes AKR1C1-AKR1C4 in Escherichia coli C41(DE3)
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stable expression of AKR1C2 and AKR1C3 in androgen insensitive human prostate cancer PC-3 cells
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transient functional expression in COS-1 cells, stable functional expression in PC-3 cells and in LNCaP cells
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
V54L
site-directed mutagenesis, the change renders the sequence identical to that of human 20-alpha hydroxysteroid dehydrogenase. The V54L mutation directly restricts the steroid binding modes to a unique one, which resembles the orientation of 20alpha-OHProg within human 20alpha-HSD. The kinetic study shows that the V54L mutation significantly decreases the 3alpha-HSD activity for the reduction of 5alpha-dihydrotestosterone, while this mutation enhances the 20alpha-HSD activity to convert progesterone
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
biotechnology
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transfection of cells with plasmids encoding a 3alpha-hydroxysteroid dehydrogenase-Del1 deposition domain fusion protein. The Del1 deposition domain immobilizes the enzyme in the extracellular matrix without interfering with its enzymatic activity. Extracellular matrix conditioned by cells transfected with 3alpha-hydroxysteroid dehydrogenase-Del1 deposition domain fusion significantly suppresses the growth of otherwise untreated LNCaP cells
medicine
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enzyme is a potential drug target