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Information on EC 1.1.1.213 - 3alpha-hydroxysteroid 3-dehydrogenase (Re-specific) and Organism(s) Rattus norvegicus and UniProt Accession P23457

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IUBMB Comments
The enzyme acts on multiple 3alpha-hydroxysteroids. Re-specific with respect to NAD+ or NADP+ [cf. EC 1.1.1.50, 3alpha-hydroxysteroid 3-dehydrogenase (Si-specific)]. Enzymes whose stereo-specificity with respect to NAD+ or NADP+ is not known are described by EC 1.1.1.357, 3alpha-hydroxysteroid 3-dehydrogenase.
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Select one or more organisms in this record: ?
This record set is specific for:
Rattus norvegicus
UNIPROT: P23457
Word Map
The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
Synonyms
dihydrodiol dehydrogenase, 3alpha-hsd, 3alpha-hydroxysteroid dehydrogenase, bile acid-binding protein, akr1c9, 3alphahsd, 3alpha-hsor, 3alpha-hydroxysteroid oxidoreductase, type 3 3alpha-hsd, alpha-hsd/cr, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
3alpha-HSOR
248
-
3alpha-hydroxysteroid dehydrogenase
3alpha-hydroxysteroid dehydrogenase (B-specific)
-
-
-
0
3alpha-hydroxysteroid oxido-reductase
248
-
3alpha-hydroxysteroid oxidoreductase
-
-
-
0
3alpha-hydroxysteroid:NAD(P) oxidoreductase
-
-
-
0
3alphaHSD
248
-
A-specific 3alpha-hydroxysteroid dehydrogenase
-
-
-
0
AKR1C17
248
-
AKR1C9
B-specific 3alpha-hydroxysteroid dehydrogenase
-
-
-
0
dihydrodiol dehydrogenase
283840
-
NAD+-dependent 3alpha-HSD
248
-
NADP(H)-dependent 3alpha-HSD
248
-
additional information
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
0
oxidation
-
-
-
0
reduction
-
-
-
0
SYSTEMATIC NAME
IUBMB Comments
3alpha-hydroxysteroid:NAD(P)+ 3-oxidoreductase (Re-specific)
The enzyme acts on multiple 3alpha-hydroxysteroids. Re-specific with respect to NAD+ or NADP+ [cf. EC 1.1.1.50, 3alpha-hydroxysteroid 3-dehydrogenase (Si-specific)]. Enzymes whose stereo-specificity with respect to NAD+ or NADP+ is not known are described by EC 1.1.1.357, 3alpha-hydroxysteroid 3-dehydrogenase.
CAS REGISTRY NUMBER
COMMENTARY hide
9028-56-2
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(11S,12S)-11,12-dihydrobenzo[g]chrysene-11,12-diol + NADP+
? + NADPH + H+
show the reaction diagram
enzyme is stereoselective for benzo[g]chrysene-11S,12S-dihydrodiol
-
-
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
show the reaction diagram
-
-
?
2 tibolone + 2 NADPH + 2 H+
3alpha-hydroxytibolone + 3beta-hydroxytibolone + 2 NADP+
show the reaction diagram
5alpha-androstan-3,17-dione + NAD(P)H
3alpha-hydroxy-5alpha-androstan-17-one + NAD(P)+
show the reaction diagram
-
-
r
benzo[c]phenanthrene-3,4-dihydrodiol + NADP+
? + NADPH + H+
show the reaction diagram
enzyme metabolizes both stereoisomers of benzo[c]phenanthrene-3,4-dihydrodiol
-
-
?
(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 + NADPH + H+
?
show the reaction diagram
-
-
-
-
r
(5beta,20R)-20-hydroxypregnan-3-one + NADH + H+
?
show the reaction diagram
-
-
-
-
r
1-(4'nitrophenyl)prop-2-en-1-ol + NAD+
1-(4'nitrophenyl)prop-2-en-1-one + NADH
show the reaction diagram
-
-
-
?
1-(4'nitrophenyl)prop-2-yn-1-ol + NAD+
1-(4'nitrophenyl)prop-2-yn-1-one + NADH
show the reaction diagram
-
-
-
?
1-acenaphthenol + NAD(P)+
1-acenaphthenone + NAD(P)+
show the reaction diagram
-
pH 9.0
-
?
1-acetophenone + NADPH
1-phenylethanol + NADP+
show the reaction diagram
-
-
-
-
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
show the reaction diagram
-
the rate of dihydrotestosterone reduction over back-conversion is 2.4 and 5.9 for prostate and epididymis, respectively
-
r
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
show the reaction diagram
17beta-hydroxy-5alpha-androstan-3-one + NADPH
3alpha,17beta-dihydroxy-5alpha-androstan + NADP+
show the reaction diagram
-
-
-
r
2-acetylpyridine + NADPH
1-(2-pyridyl)ethanol + NADP+
show the reaction diagram
-
stereoselective catalysis producing mainly the (S)-alcohols
-
-
?
2-decalone + NADH
? + NAD+
show the reaction diagram
-
pH 6.0
-
?
3-acetylpyridine + NADPH
1-(3-pyridyl)ethanol + NADP+
show the reaction diagram
-
low activity, stereoselective catalysis producing mainly the (S)-alcohols
-
-
?
3alpha,5alpha-allopregnenolone + NAD(P)+
5alpha-dihydroprogesterone + NAD(P)H
show the reaction diagram
3alpha-androstanediol + NAD+
5alpha-dihydrotestosterone + NADH + H+
show the reaction diagram
-
steroid reduction direction is preferred
-
-
r
3alpha-hydroxy-5alpha-androstan-17-one + NAD+
5alpha-androstan-3,17-dione + NADH
show the reaction diagram
4'-methoxyacetophenone + NADPH + H+
1-(4-methoxyphenyl)ethanol + NADP+
show the reaction diagram
-
-
R,S-enantiomeric product
-
?
4-acetylpyridine + NADPH
(S)-1-(4-pyridyl)ethanol + NADP+
show the reaction diagram
-
-
-
-
?
4-acetylpyridine + NADPH
1-(4-pyridyl)ethanol + NADP+
show the reaction diagram
-
stereoselective catalysis producing mainly the (S)-alcohols
-
-
?
4-androsten-3alpha-ol-17-one + NADH + H+
4-androsten-3alpha,17beta-diol + NAD+
show the reaction diagram
-
AKR1C17
-
-
r
4-androstene-3,17-dione + NADH + H+
4-androsten-3alpha-ol-17-one + NAD+
show the reaction diagram
-
low activity
-
-
r
4-bromoacetophenone + NADPH + H+
1-(4-bromophenyl)ethanol + NADP+
show the reaction diagram
-
-
-
-
?
4-cyanoacetophenone + NADPH + H+
1-(4-cyanophenyl)ethanol + NADP+
show the reaction diagram
-
-
-
-
?
4-methylacetophenone + NADPH + H+
1-(4-methylphenyl)ethanol + NADP+
show the reaction diagram
-
-
R,S-enantiomeric product
-
?
4-nitroacetophenone + NAD(P)H
1-(4-nitrophenyl)ethanol + NAD(P)+
show the reaction diagram
-
pH 6.0
-
?
4-nitroacetophenone + NADPH + H+
1-(4-nitrophenyl)ethanol + NADP+
show the reaction diagram
-
-
-
-
?
4-nitrobenzaldehyde + NAD(P)H
(4-nitrophenyl)methanol + NAD(P)+
show the reaction diagram
5alpha-androstan-3,17-dione + NAD(P)H
3alpha-hydroxy-5alpha-androstan-17-one + NAD(P)+
show the reaction diagram
-
pH 6.0 for reduction, pH 7.0 and 9.0 for androsterone oxidation
-
r
5alpha-androstan-3alpha-ol-17-one + NADH + H+
5beta-androstan-3alpha,17beta-diol + NAD+
show the reaction diagram
-
-
-
-
r
5alpha-androstane-3,17-dione + NADH
5alpha-androstan-3alpha-ol-17-one + NAD+
show the reaction diagram
-
low activity
AKR1C9
-
r
5alpha-dihydrotestosterone + NADH
?
show the reaction diagram
-
low activity
-
-
?
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
show the reaction diagram
5alpha-dihydrotestosterone + NADPH + H+
3alpha-androstanediol + NADP+
show the reaction diagram
5alpha-pregnan-3,20-dione + NAD(P)H + H+
5alpha-pregnan-3alpha-ol-20-one + NAD(P)+
show the reaction diagram
-
regulation of the amount of allosteric agonists that can bind to the GABA receptor in brain
-
r
5alpha-pregnane-20alpha-ol-3-one + NADH
5alpha-pregnane-3,20alpha-diol + NAD+
show the reaction diagram
-
-
-
-
?
5alpha-pregnane-3,20-dione + NADH
5alpha-pregnan-3alpha-ol-20-one + NAD+
show the reaction diagram
-
low activity
-
-
r
5beta-androstan-3alpha-ol-17-one + NAD(P)+
5beta-androstane-3,17-dione + NAD(P)H
show the reaction diagram
-
-
-
-
r
5beta-androstan-3alpha-ol-17-one + NADH
5beta-androstane-3alpha,17beta-diol + NAD+
show the reaction diagram
-
-
-
-
r
5beta-androstane-3,17-dione + NADH
5beta-androstan-3alpha-ol-17-one + NAD+
show the reaction diagram
-
-
-
-
r
5beta-pregnan-3alpha-ol-20-one + NAD(P)+
5beta-pregnane-3,20-dione + NAD(P)H
show the reaction diagram
-
-
-
-
r
5beta-pregnane-17alpha,20beta,21-triol-3,11-dione + NAD(P)H
5beta-pregnane-3alpha,17alpha,20beta,21-tetraol-11-one + NAD(P)+
show the reaction diagram
5beta-pregnane-20alpha-ol-3-one + NADH + H+
5beta-pregnane-3,20alpha-diol + NAD+
show the reaction diagram
-
-
-
-
?
5beta-pregnane-3,20-dione + NADH + H+
5beta-pregnan-3alpha-ol-20-one + NAD+
show the reaction diagram
-
-
-
-
r
6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one + NADH
?
show the reaction diagram
-
the enzyme produces both R- and S-form products in a ratio of 2.3 : 1
-
-
?
7alpha,12alpha-dihydroxy-5beta-cholestan-3-one + NADPH + H+
5beta-cholestane-3alpha,7alpha,12alpha-triol + NADP+
show the reaction diagram
-
-
-
-
?
7alpha-hydroxy-5beta-cholestan-3-one + NADPH + H+
5beta-cholestane-3alpha,7alpha-diol + NADP+
show the reaction diagram
-
-
-
-
?
9,10-phenanthrenequinone + NAD(P)H
? + NAD(P)+
show the reaction diagram
9,10-phenanthrenequinone + NADH
?
show the reaction diagram
-
-
-
-
?
acetophenone + NADPH
1-phenylethanol + NADP+
show the reaction diagram
-
-
-
-
?
androstan-17beta-ol-3-one + NADH
androstan-3alpha,17beta-diol + NAD+
show the reaction diagram
-
-
-
?
androstan-3,17-dione + NADH
androstan-3alpha-ol-17-one + NAD+
show the reaction diagram
-
-
-
?
androsterone + NAD(P)+
5alpha-androstane-3,17-dione + NAD(P)H
show the reaction diagram
-
-
-
-
r
androsterone + NADP+
5alpha-androstane-3,17-dione + NADPH
show the reaction diagram
-
-
-
-
r
benzenedihydrodiol + NAD(P)+
? + NAD(P)+
show the reaction diagram
-
pH 9.0
-
?
beta-muricholic acid + NADH
?
show the reaction diagram
-
low activity
-
-
?
chenodeoxycholic acid + NADH
?
show the reaction diagram
-
-
-
-
?
cholic acid + NADH
?
show the reaction diagram
-
low activity
-
-
?
dehydrolithocholic acid + NADH + H+
?
show the reaction diagram
-
-
-
-
?
deoxycholic acid + NADH
?
show the reaction diagram
-
low activity
-
-
?
diacetyl + NADH
?
show the reaction diagram
-
-
-
-
?
etiocholane-3,17-dione + NADH
etiocholan-3alpha-ol-17-one + NAD+
show the reaction diagram
-
-
-
?
glycochenodeoxycholic acid + NADH
?
show the reaction diagram
-
-
-
-
?
glycolithocholic acid + NADH
?
show the reaction diagram
-
-
-
-
?
glycoursodeoxycholic acid + NADH
?
show the reaction diagram
-
-
-
-
?
hyodeoxycholic acid + NADH
?
show the reaction diagram
-
low activity
-
-
?
isatin + NADH
?
show the reaction diagram
-
-
-
-
?
lithocholic acid + NADH
?
show the reaction diagram
-
-
-
-
?
murocholic acid + NADH
?
show the reaction diagram
-
low activity
-
-
?
pregnane-11beta,17alpha,21-triol-3,20-dione + NADH
pregnane-3alpha,11beta,17alpha,21-tetrol-20-one + NAD+
show the reaction diagram
-
-
-
?
progesterone + NAD(P)H
3alpha-hydroxy-pregn-4-ene-20-one + NAD(P)+
show the reaction diagram
-
-
-
-
r
prostaglandin + NADP+
? + NADPH
show the reaction diagram
-
types A1, A2, B1, B2, D2, E1, E2, F1, F2alpha and 15-keto-prostaglandinE2 and F2alpha
-
?
prostaglandin-F2alpha + NADP+
prostaglandin F2 + prostaglandin B2 + NADPH
show the reaction diagram
-
-
-
?
taurolithocholic acid + NADH
?
show the reaction diagram
-
-
-
-
?
tauroursodeoxycholic acid + NADH
?
show the reaction diagram
-
-
-
-
?
testosterone + NAD(P)H + H+
4-androsten-3alpha,17beta-diol + NAD(P)+
show the reaction diagram
-
-
-
-
r
testosterone + NADH
?
show the reaction diagram
-
low activity
-
-
?
ursodeoxycholic acid + NADH
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
show the reaction diagram
-
-
?
2 tibolone + 2 NADPH + 2 H+
3alpha-hydroxytibolone + 3beta-hydroxytibolone + 2 NADP+
show the reaction diagram
i.e. tibolone, a 3-ketosteroid androgen receptor, conversion to potent estrogen receptor alpha agonists, tibolone induces estrogen receptor alpha-dependent gene promoter activity through cis-acting estrogen response elements, increases the stimulatory effect of TGF-beta on Smad-dependent gene promoter activity, and enhances prostaglandin E2-induced activity of transcription factor Runx2, overview
3alpha-hydroxytibolone is the primary metabolite
-
r
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
show the reaction diagram
3alpha,5alpha-allopregnenolone + NAD(P)+
5alpha-dihydroprogesterone + NAD(P)H
show the reaction diagram
-
i.e. 3alpha,5alpha-tetrahydroprogesterone or 3alpha,5alpha-THP, the enzyme catalyzes the biosynthesis and oxidation of 3alpha,5alpha-reduced neurosteroids as allopregnanolone, which stimulates GABAA receptors, sciatic nerves-induced analgesia results in increased enzyme levels in neuropathic rats, overview
-
-
r
3alpha-androstanediol + NAD+
5alpha-dihydrotestosterone + NADH + H+
show the reaction diagram
-
steroid reduction direction is preferred
-
-
r
4-acetylpyridine + NADPH
(S)-1-(4-pyridyl)ethanol + NADP+
show the reaction diagram
-
-
-
-
?
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
show the reaction diagram
-
-
-
-
?
5alpha-dihydrotestosterone + NADPH + H+
3alpha-androstanediol + NADP+
show the reaction diagram
-
steroid reduction direction is preferred
-
-
r
5alpha-pregnan-3,20-dione + NAD(P)H + H+
5alpha-pregnan-3alpha-ol-20-one + NAD(P)+
show the reaction diagram
-
regulation of the amount of allosteric agonists that can bind to the GABA receptor in brain
-
r
5beta-pregnane-17alpha,20beta,21-triol-3,11-dione + NAD(P)H
5beta-pregnane-3alpha,17alpha,20beta,21-tetraol-11-one + NAD(P)+
show the reaction diagram
-
hepatic reduction in animal tissues
-
?
acetophenone + NADPH
1-phenylethanol + NADP+
show the reaction diagram
-
-
-
-
?
androsterone + NADP+
5alpha-androstane-3,17-dione + NADPH
show the reaction diagram
-
-
-
-
r
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NAD(P)+
NAD(P)H
NADP+
NADPH
additional information
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
non-metallo enzyme
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
DMSO
33% inhibition
naphthalene-1,2-dione
naphthalene-1,2-dione leads to the time and concentration dependent irreversible inactivation of AKR1C9 via alkylation
(E/Z)-sulfindac
-
wild-type, W86Y and W227Y
1,10-phenanthroline
-
wild-type, W86Y and W227Y
1,7-phenanthroline
-
wild-type, W86Y and W227Y
1-(4'nitrophenyl)prop-2-en-1-ol
-
inactivation dependent on NAD+ concentration, optimal at 0.5-1.0 mM NAD+, 2-mercaptoethanol prvides a concentration-dependent protection
1-(4'nitrophenyl)prop-2-en-1-one
-
inactivation can be retarded markedly in a concentration-dependent manner by both NADH and NADPH. Competitive inhibitor of NAD+ binding, measured for androsterone oxidation
1-(4'nitrophenyl)prop-2-yn-1-one
-
competitive inhibitor of NAD+ binding, measured for androsterone oxidation
17beta-bromoacetoxy-5alpha-dihydrotestosterone
-
inactivation by modification of steroid-binding site
4-androstene-3,17-dione
-
versus substrate, the products, 4-androstene-3,17-dione and NADH, inhibit the activity uncompetitively and competitively, respectively, with respect to NAD+ in the presence of a saturated concentration of 0.004 mM of the substrate
6alpha-Methylprednisolone
-
-
acetaminophen
-
non-competitive, only androsterone oxidation, pH 7.0
acetylenic ketones
-
inactivation by forming Michael adducts with enzyme nucleophiles
-
arachidonic acid
-
-
aspirin
-
salicylate, non-competitive, only androsterone oxidation, pH 7.0
Betamethasone
-
non-competitive
cacodylate
-
-
cortisol
-
competitive
cortisone
-
competitive
Cu2+
-
100% inhibition at 0.1 mM
D-glucose 6-phosphate
-
-
dexamethasone
-
non-competitive
Flufenamic acid
-
wild-type, W86Y and W227Y
Hexestrol
-
-
Ibuprofen
-
competitive
indomethacin
iodoacetate
-
50% inhibition at 0.1 mM
Ketamine
-
specific inhibitor for AKR1C17, but no inhibition of AKR1C9
Meclofenamic acid
Mefenamic acid
-
wild-type, W86Y and W227Y
NADH
-
the products, 4-androstene-3,17-dione and NADH, inhibit the activity uncompetitively and competitively, respectively, with respect to NAD+ in the presence of a saturated concentration of 0.004 mM of the substrate
non-steroidal anti-inflamatory drug
-
Oxyphenybutazone
-
competitive
p-chloromercuribenzoate
-
non-competitive with respect to dihydrocortisone 46-100% inhibition at 0.01 mM, preincubation with NADH lowers the inhibitory effect
ponalrestat
-
wild-type, W86Y and W227Y, weak inhibitor
Prednisolone
-
competitive
Prednisone
-
competitive
progesterone
-
competitive to testosterone
Prostaglandin
prostaglandin A1
-
-
prostaglandin A2alpha
-
-
Prostaglandin B1
-
-
prostaglandin E1
-
-
prostaglandin F1alpha
-
-
pyrazole
-
10% at 0.4 mM
salicylate
-
non-competitive
testosterone
Tolmetin
-
competitive, only androsterone oxidation, pH 7.0
Zomepirac
-
competitive, only androsterone oxidation, pH 7.0
zopolrestat
additional information
-
not inhibited by dicoumarol, disulfiram and barbiturates. Inhibitory potency of non-steroidal anti-inflamatory drugs and salicylates falls sharply as the pH is increased from 6 to 9
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
prostaglandin E2 increases AKR1C9 gene promoter activity and mRNA expression, AKR1C9 promoter activity is also enhanced by overexpression of protein kinase A catalytic subunit or transcription factor C/EBPdelta, whicb is reduced by dominant negative C/EBPdelta competition or C/EBPdelta antisense expression, overview
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0013 - 0.0441
3alpha-hydroxy-5alpha-androstan-17-one
0.0011 - 0.0304
5alpha-Androstan-3,17-dione
0.004 - 0.821
NAD+
-
0.0057 - 0.0312
NADH
-
0.0052 - 0.1515
NADP+
-
0.0022 - 0.0081
NADPH
-
0.0027
(5beta,20R)-20-hydroxypregnan-3-one
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.0012 - 0.726
17beta-hydroxy-5alpha-androstan-3-one
3.54 - 33.7
2-decalone
-
-
0.029 - 0.408
3alpha-hydroxy-5alpha-androstan-17-one
0.163 - 0.211
4-nitrobenzaldehyde
-
-
0.0017 - 0.0042
5alpha-Androstan-3,17-dione
0.00065
5alpha-androstane-3,17-dione
-
pH 7.0, 25, reduction reaction
0.781 - 7.331
5alpha-androstane-3alpha,17beta-diol
0.0021
5beta-androstane-3,17-dione
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.01
5beta-pregnane-17alpha,20beta,21-triol-3,11-dione
-
-
0.0024
5beta-pregnane-3,20-dione
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.023
6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.00122 - 0.038
9,10-phenanthrenequinone
0.0041
androsterone
-
pH 7.0, 25, oxidation reaction
0.004
Dehydrolithocholic acid
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.42
diacetyl
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.022
isatin
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.04 - 0.94
NAD+
0.015 - 0.033
NADH
0.04
NADP+
-
-
0.0001
Prostaglandin
-
-
additional information
(11S,12S)-11,12-dihydrobenzo[g]chrysene-11,12-diol
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00063 - 0.85
(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
0.115
(5beta,20R)-20-hydroxypregnan-3-one
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
1.13 - 1.25
3alpha-hydroxy-5alpha-androstan-17-one
0.267 - 0.283
5alpha-Androstan-3,17-dione
0.42
5alpha-androstane-3,17-dione
-
pH 7.0, 25, reduction reaction
0.037 - 0.43
5alpha-dihydroprogesterone
0.047
5beta-androstane-3,17-dione
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.105
5beta-pregnane-3,20-dione
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.1
6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.183 - 3.93
9,10-phenanthrenequinone
0.0053 - 0.83
androsterone
0.022
Dehydrolithocholic acid
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.167
diacetyl
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.283
isatin
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
1.13 - 1.43
NAD+
0.283 - 0.367
NADH
additional information
additional information
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0022 - 0.018
4-androstene-3,17-dione
0.0075
6alpha-Methylprednisolone
-
androsterone oxidation
0.006
arachidonic acid
0.65
aspirin
-
for androsterone oxidation
0.0045
Betamethasone
-
androsterone oxidation
0.19
cortisol
-
androsterone oxidation
0.285
cortisone
-
androsterone oxidation
0.01
dexamethasone
-
androsterone oxidation
0.0002 - 0.001
indomethacin
0.017
NADH
-
-
0.0175
Prednisolone
-
androsterone oxidation
0.0175
Prednisone
-
androsterone oxidation
0.0031
prostaglandin A1
-
androsterone oxidation
0.003
prostaglandin A2alpha
-
-
0.0008
Prostaglandin B1
-
androsterone oxidation
0.0075
prostaglandin E1
-
androsterone oxidation
0.012
prostaglandin F1alpha
-
androsterone oxidation
0.115 - 0.75
salicylate
-
-
additional information
additional information
-
more Ki values given for different inhibitors of androsterone oxidation, 9,10-phenanthrenequinone- and 5alpha-androstane-3,17-dione reduction
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000735 - 0.00333
indomethacin
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.08
Q190A mutant, androsterone oxidation with NAD+
0.1
S166A mutant, androsterone oxidation with NAD+
0.81
Y216S mutant, androsterone oxidation with NADP+
1.55
recombinant wild type enzyme, androsterone oxidation with NAD+
1.6
wild type homogeneous recombinant AKR1C9, at 25°C
0.0005 - 0.0053
-
for prostaglandins A1, A2, B1, B2, D2, E1, E2, F1, F2alpha at concentrations of 0.06 mM
0.0007 - 0.0012
-
for 15-keto-prostaglandins E2 and F2alpha at concentrations of 0.06 mM
0.006
-
purified recombinant mutant W227A, substrate androsterone
0.008 - 4
-
determined for several substrates,with best activities for 9,10-phenanthrenequinone, 4-nitrobezaldehyde and androsterone
0.01
-
purified recombinant mutant F118A, substrate androsterone
0.03
-
purified recombinant mutant F129A, substrate androsterone
0.059
-
W86Y mutant
0.07
-
recombinant AKR1C17 in cell extract, substrate 4-androsten-3alpha-ol-17-one
0.09
-
purified recombinant mutant N306A, substrate androsterone
0.1
-
purified recombinant mutant Y310A, substrate androsterone
0.23
-
purified recombinant AKR1C17, substrate 4-androsten-3alpha-ol-17-one
0.674
-
W148Y mutant
0.86
-
purified recombinant mutant T24A, substrate androsterone
0.96
-
purified recombinant mutant T226A, substrate androsterone
1.5
-
native enzyme
1.6
-
purified recombinant wild-type enzyme, substrate androsterone
2
-
for androsterone
9540
-
purified enzyme
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4 - 9.5
-
recombinant enzyme
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 11
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
lumbar, of naive, sham-operated and neuropathic rats, enzyme expression analysis and cellular distribution in neurons and glial cells, immunohistochemic analysis, overview
Manually annotated by BRENDA team
-
abundant enzyme expression
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
DIDH_RAT
322
0
37028
Swiss-Prot
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37000
1 * 37000, SDS-PAGE
33000
33500
-
1 * 33500, SDS-PAGE
34000
34600
-
gel filtration
36000
-
recombinant AKR1C17, gel filtration
37000
37029
-
1 * 37029
37030
-
predicted molecular weight from the cDNA
74000 - 75000
-
native PAGE, kidney enzyme
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
1 * 37000, SDS-PAGE
monomer
additional information
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
vapor diffusion techniques using ammonium sulfate as precipitant
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
F118A
largest changes in kcat/Km
F129A
largest changes in kcat/Km, F129A alters the stereochemical preference from oxidizing predominantly the S,S-stereoisomer to oxidizing predominantly the R,R-stereoisomer of benzo[g]chrysene-11,12-dihydrodiol
L54A
mutant shows intermediate changes in kcat/Km versus wild type
N167A
site-directed mutagenesis, most impaired enzyme
N306A
mutant shows intermediate changes in kcat/Km versus wild type
Q190A
site-directed mutagenesis, decreased binding affinity to NADP(H), only binding of cofactor is affected, residue is located at the catalytic cente
R276M
elimination of salt bridge between Arg276 and the 2'-phosphate of AMP results in 100fold decrease of the affinity to NADP(H)
S166A
site-directed mutagenesis, decreased binding affinity to NADP(H), only binding of cofactor is affected, residue is located at the catalytic center
T226A
smallest change in kcat/Km is observed when alanine is used to substitute hydrophilic residues
T24A
smallest change in kcat/Km is observed when alanine is used to substitute hydrophilic residues
W227A
largest changes in kcat/Km
Y216S
site-directed mutagenesis, decreased binding affinity to NADP(H), only binding of cofactor is affected, residue is located at the catalytic cente
Y310A
mutant shows intermediate changes in kcat/Km versus wild type
C217A
-
resistant to inactivation by secosteroids, therefore Cys217 is the point of covalent attachment of acetylenic ketones
D50E
-
1/30th catalytic efficiency of wild type, unlikely to be the general amino acid for catalysis
D50N
-
1/30th catalytic efficiency of wild type, unlikely to be the general amino acid for catalysis
E276R
-
site-directed mutagenesis, the mutation alters the cofactor specificity of AKR1C17 from NAD+ to NADP+, the switch is analogy th the residues of AKRc9 and its cofactor specificity, overview
F118A
-
site-directed mutagenesis, highly reduced activity compared to the wild-type enzyme, effects of mutation on binding constants and kinetics, overview
F129A
-
site-directed mutagenesis, highly reduced activity compared to the wild-type enzyme, effects of mutation on binding constants and kinetics, overview
H117A
-
1/500th catalytic efficiency of wild type, unlikely to be the general amino acid for catalysis
K84M
-
inactive, unable to bind steroids
K84R
-
inactive, unable to bind steroids
L54A
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme, effects of mutation on binding constants and kinetics, overview
N306A
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme, effects of mutation on binding constants and kinetics, overview
Q270K
-
site-directed mutagenesis, the mutation alters the cofactor specificity of AKR1C17 from NAD+ to NADP+, the switch is analogy th the residues of AKRc9 and its cofactor specificity, overview
Q270K/E276R
-
site-directed mutagenesis, the mutation alters the cofactor specificity of AKR1C17 from NAD+ to NADP+, the switch is analogy th the residues of AKRc9 and its cofactor specificity, overview
R276E
-
site-directed mutagenesis, the mutant shows increased preference for the oxidation reaction compared to the wild-type enzyme
R276G
-
site-directed mutagenesis, the mutant shows slightly increased preference for the reduction reaction compared to the wild-type enzyme
R276M
T226A
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme, effects of mutation on binding constants and kinetics, overview
T24A
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme, effects of mutation on binding constants and kinetics, overview
W148Y
W227A
W227Y
Y205F
-
kinetically indistinguishable from the wild type, no general amino acid for catalysis in 3alpha-hydroxysteroid dehydrogenase
Y310A
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme, effects of mutation on binding constants and kinetics, overview
Y55F
-
inactive, unable to perform steroid oxidoreduction, strongest candidate for the general amino acid
Y55S
-
inactive, strongest candidate for the general amino acid
additional information
-
positions of Tyr/Lys pair are conserved across the aldo-keto reductase and short-chain dehydrogenase/reductase family. Tyr retains ability to form ternary complex and acts as general acid
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-10°C, 3 weeks, activity declines about 50%
-
-10°C, most purified preparation, 5 days, loses between 80% and 100% of activity
-
-70°C, 20 mM potassium phosphate buffer, pH 7.0, 1 mM EDTA, 1 mM beta-mercaptoethanol, 30% glycerol
-
-80°C, 20 mM potassium phosphate buffer, pH 7.0, 1 mM EDTA, 1 mM DTT, 30% glycerol
-
3°C, first ammonium sulfate fraction, stable at least 3 weeks
-
3°C, most purified preparation, 5 days, loses 50% of activity
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
anion exchange and Blue Sepharose column
N167A chromatofocusing and gel filtration introduced between the to others chromatography steps
purification of recombinant wild type and mutants of AKR1C9
ammonium sulfate precipitation, Ca2(PO4)2 gel extraction, ethanol precipitation
-
anion exchange and Blue Sepharose column
-
CaCl2 and ammonium sulfate fractionation, DEAE-cellulose- and hydroxyapatite chromatography, chromatofocusing, Sephadex G-100
-
native enzyme 73.3fold from liver by ammonium sulfate, anion-exchange chromatography, gel filtration, and affinity chromatography
-
recombinant wild-type and mutant AKR1C17s from Escherichia coli strain BL21(DE3)
-
recombinant wild-type and mutant enzymes from Escherichia coli C41(DE3), to homogeneity
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression and promoter activity analysis, genetic enzyme regulation, overview
expression of recombinant wild type and mutants of AKR1C9
expression of wild-type and mutant AKR1C17s in Escherichia coli strain BL21(DE3)
-
full-length cDNA gene is expressed in Escherichia coli DH5alpha
-
overexpression of AKR1C9 in Escherichia coli
-
overexpression of wild-type and mutant enzymes in Escherichia coli C41(DE3)
-
plasmid DNA containing cDNA is transformed in Escherichia coli HB101, cDNA is used for sequencing
-
stable expression of wild-type and mutant enzymes in HEK-293 cells
-
wild-type enzyme and mutants are overexpressed in Escherichia coli DH5alpha
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
-
the enzyme is a target for treatment of chronic pain in neuropathic diseases, overview
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Askonas, L.J.; Ricigliano, J.W.; Penning, T.M.
The kinetic mechanism catalysed by homogeneous rat liver 3alpha-hydroxysteroid dehydrogenase. Evidence for binary and ternary dead-end complexes containing non-steroidal anti-inflammatory drugs
Biochem. J.
278
835-841
1991
Rattus norvegicus
Manually annotated by BRENDA team
Penning, T.M.; Sharp, R.B
Prostaglandin dehydrogenase activity of purified rat liver 3alpha-hydroxysteroid dehydrogenase
Biochem. Biophys. Res. Commun.
148
646-652
1987
Rattus norvegicus
Manually annotated by BRENDA team
Pawlowski, J.E.; Huizinga, M.; Penning, T.M.
Cloning and sequencing of the cDNA for rat liver 3alpha-hydroxysteroid/dihydrodiol dehydrogenase
J. Biol. Chem.
266
8820-8825
1991
Rattus norvegicus, Rattus norvegicus Sprangue-Dawley
Manually annotated by BRENDA team
Penning, T.M.; Mukharji, I.; Barrows, S.; Talalay, P.
Purification and properties of a 3alpha-hydroxysteroid dehydrogenase of rat liver cytosol and its inhibition by anti-inflammatory drugs
Biochem. J.
222
601-611
1984
Rattus norvegicus, Rattus norvegicus Sprangue-Dawley
Manually annotated by BRENDA team
Tomkins, G.M.
A mammalian 3alpha-hydroxysteroid dehydrogenase
J. Biol. Chem.
218
437-447
1956
Rattus norvegicus
Manually annotated by BRENDA team
Ricigliano, J.W.; Penning, T.M.
Evidence that enzyme-generated aromatic Michael acceptors covalently modify the nucleotide-binding site of 3alpha-hydroxysteroid dehydrogenase
Biochem. J.
269
749-755
1990
Rattus norvegicus, Rattus norvegicus Sprangue-Dawley
Manually annotated by BRENDA team
Span, P.N.; Sweep, C.G.J.; Benraad, T.J.; Smals, A.G.H.
3alpha-Hydroxysteroid oxidoreductase activities in dihydrotestosterone degradation and back-formation in rat prostate and epididymis
J. Steroid Biochem. Mol. Biol.
58
319-324
1996
Rattus norvegicus
Manually annotated by BRENDA team
Jez, J.M.; Schlegel, B.P.; Penning, T.M.
Characterization of the substrate binding site in rat liver 3alpha-hydroxysteroid/dihydrodiol dehydrogenase. The roles of tryptophans in ligand binding and protein fluorescence
J. Biol. Chem.
271
30190-30198
1996
Rattus norvegicus
Manually annotated by BRENDA team
Penning, T.M.; Bennett, M.J.; Smith-Hoog, S.; Schlegel, B.P.; Jez, J.M.; Lewis, M.
Structure and function of 3alpha-hydroxysteroid dehydrogenase
Steroids
62
101-111
1997
Rattus norvegicus
Manually annotated by BRENDA team
Ma, H.; Ratnam, K.; Penning, T.M.
Mutation of nicotinamide pocket residues in rat liver 3alpha-hydroxysteroid dehydrogenase reveals different modes of cofactor binding
Biochemistry
39
102-109
2000
Rattus norvegicus (P23457)
Manually annotated by BRENDA team
Heredia, V.V.; Penning, T.M.
Dissection of the physiological interconversion of 5alpha-DHT and 3alpha-diol by rat 3alpha-HSD via transient kinetics shows that the chemical step is rate-determining: effect of mutating cofactor and substrate-binding pocket residues on catalysis
Biochemistry
43
12028-12037
2004
Rattus norvegicus
Manually annotated by BRENDA team
Heredia, V.V.; Cooper, W.C.; Kruger, R.G.; Jin, Y.; Penning, T.M.
Alanine scanning mutagenesis of the testosterone binding site of rat 3alpha-hydroxysteroid dehydrogenase demonstrates contact residues influence the rate-determining step
Biochemistry
43
5832-5841
2004
Rattus norvegicus
Manually annotated by BRENDA team
Uwai, K.; Konno, N.; Kitamura, S.; Ohta, S.; Takeshita, M.
Purification and characterization of rat liver enzyme catalyzing stereoselective reduction of acetylpyridines
Chirality
17
494-500
2005
Rattus norvegicus
Manually annotated by BRENDA team
Papari-Zareei, M.; Brandmaier, A.; Auchus, R.J.
Arginine 276 controls the directional preference of AKR1C9 (rat liver 3alpha-hydroxysteroid dehydrogenase) in human embryonic kidney 293 cells
Endocrinology
147
1591-1597
2006
Rattus norvegicus
Manually annotated by BRENDA team
Sanai, M.; Endo, S.; Matsunaga, T.; Ishikura, S.; Tajima, K.; El-Kabbani, O.; Hara, A.
Rat NAD+-dependent 3alpha-hydroxysteroid dehydrogenase (AKR1C17): a member of the aldo-keto reductase family highly expressed in kidney cytosol
Arch. Biochem. Biophys.
464
122-129
2007
Rattus norvegicus
Manually annotated by BRENDA team
Uwai, K.; Konno, N.; Yasuta, Y.; Takeshita, M.
Electronic effects of para-substitution on acetophenones in the reaction of rat liver 3alpha-hydroxysteroid dehydrogenase
Bioorg. Med. Chem.
16
1084-1089
2008
Rattus norvegicus
Manually annotated by BRENDA team
Cooper, W.C.; Jin, Y.; Penning, T.M.
Elucidation of a complete kinetic mechanism for a mammalian hydroxysteroid dehydrogenase (HSD) and identification of all enzyme forms on the reaction coordinate: the example of rat liver 3alpha-HSD (AKR1C9)
J. Biol. Chem.
282
33484-33493
2007
Rattus norvegicus
Manually annotated by BRENDA team
McCarthy, T.L.; Hochberg, R.B.; Labaree, D.C.; Centrella, M.
3-ketosteroid reductase activity and expression by fetal rat osteoblasts
J. Biol. Chem.
282
34003-34012
2007
Rattus norvegicus (P23457)
Manually annotated by BRENDA team
Azzarello, J.; Fung, K.M.; Lin, H.K.
Tissue distribution of human AKR1C3 and rat homolog in adult genitourinary system
J. Histochem. Cytochem.
56
853-861
2008
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Meyer, L.; Venard, C.; Schaeffer, V.; Patte-Mensah, C.; Mensah-Nyagan, A.G.
The biological activity of 3alpha-hydroxysteroid oxido-reductase in the spinal cord regulates thermal and mechanical pain thresholds after sciatic nerve injury
Neurobiol. Dis.
30
30-41
2008
Rattus norvegicus
Manually annotated by BRENDA team
Shultz, C.A.; Palackal, N.T.; Mangal, D.; Harvey, R.G.; Blair, I.A.; Penning, T.M.
Fjord-region benzo[g]chrysene-11,12-dihydrodiol and benzo[c]phenanthrene-3,4-dihydrodiol as substrates for rat liver dihydrodiol dehydrogenase (AKR1C9): structural basis for stereochemical preference
Chem. Res. Toxicol.
21
668-677
2008
Rattus norvegicus (P23457)
Manually annotated by BRENDA team
Björkhem, I.; Danielsson, H.
Stereochemistry of hydrogen transfer from pyridine nucleotides catalyzed by delta-4-3-oxosteroid 5-beta-reductase and 3-alpha-hydroxysteroid dehydrogenase from rat liver
Eur. J. Biochem.
12
80-4
1970
Rattus norvegicus
Manually annotated by BRENDA team
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