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Information on EC 1.1.1.213 - 3alpha-hydroxysteroid 3-dehydrogenase (Re-specific)
for references in articles please use BRENDA:EC1.1.1.213
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EC Tree 1 Oxidoreductases
1.1 Acting on the CH-OH group of donors
1.1.1 With NAD+ or NADP+ as acceptor
1.1.1.213 3alpha-hydroxysteroid 3-dehydrogenase (Re-specific)
IUBMB Comments
The enzyme acts on multiple 3α-hydroxysteroids. Re-specific with respect to NAD+ or NADP+ [cf. EC 1.1.1.50, 3α-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, 3α-hydroxysteroid 3-dehydrogenase.
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
- 1.1.1.213
-
aldo-keto
- androgen
-
5alpha-reductase
-
polycyclic
-
17beta-hydroxysteroid
- 5alpha-dihydrotestosterone
-
alpha-hydroxysteroids
- dihydrotestosterone
- androsterone
- 17beta-hsd
-
trans-dihydrodiols
- hydroxysteroids
-
20alpha-hydroxysteroid
-
5alpha-dht
-
neurosteroids
- allopregnanolone
- 20alpha-hsds
- akr1c9
-
3alpha-diol
- o-quinones
- 5alpha-androstane-3alpha,17beta-diol
- 3alpha-androstanediol
-
i-babp
-
1.1.1.50
- testosteroni
-
17beta
-
5alpha-reduced
-
alicyclic
- 5alpha-dihydroprogesterone
- 20alpha-hydroxyprogesterone
-
neurosteroidogenic
- drug development
- diagnostics
- medicine
- synthesis
showSynonyms
dihydrodiol dehydrogenase, 3alpha-hsd, 3alpha-hydroxysteroid dehydrogenase, bile acid-binding protein, 3alphahsd, type 3 3alpha-hsd, alpha-hsd/cr, akr1c17, 3alpha-hydroxysteroid oxido-reductase, 3alpha-hsd type 3, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
3alpha-HSD
3alpha-hydroxysteroid dehydrogenase
3alpha-hydroxysteroid dehydrogenase (B-specific)
-
-
-
-
3alpha-hydroxysteroid oxidoreductase
-
-
-
-
3alpha-hydroxysteroid:NAD(P) oxidoreductase
-
-
-
-
3alphaHSD
A-specific 3alpha-hydroxysteroid dehydrogenase
-
-
-
-
AKR1C2
AKR1C3
AKR1C9
B-specific 3alpha-hydroxysteroid dehydrogenase
-
-
-
-
type 2 3alpha-hydroxysteroid dehydrogenase/type 5 17beta-hydroxysteroid dehydrogenase
-
-
type 3 3alpha-hydroxysteroid dehydrogenase
additional information
3alpha-hydroxysteroid dehydrogenase
-
-
-
-
additional information
-
cf. EC 1.1.1.50, the enzyme belongs to the short chain dehydrogenase/reductase protein superfamily
additional information
-
the enzyme belongs to the short-chain dehydrogenase/reductase family
additional information
-
cf. EC 1.1.1.50, the enzyme belongs to the aldo-keto reductase subfamily AKR1C
additional information
-
cf. EC 1.1.1.50, the enzyme belongs to the aldo-keto reductase, AKR, superfamily
additional information
cf. EC 1.1.1.239, the enzyme belongs to the AKR1C subfamily
additional information
the enzyme is a member of the aldo-keto reductase family
additional information
-
cf. EC 1.1.1.50, the enzyme belongs to the AKR1C family
additional information
-
cf. EC 1.1.1.50, the enzyme belongs to the short-chain dehydrogenase/reductase family
additional information
-
cf. EC 1.1.1.50, the enzyme is a member of the aldo-keto reductase superfamily
additional information
-
see also EC 1.1.1.50, 3alpha-hydroxysteroid dehydrogenase (B-specific), for enzymes catalyzing the same reaction, but which are B-specific with respect to hydrogen transfer to/from NAD(P)+/NAD(P)H. Enzymes without information of stereospecificity are summarized under EC 1.1.1.50, but may in fact belong to EC 1.1.1.213
additional information
-
see also EC 1.1.1.50, 3alpha-hydroxysteroid dehydrogenase (B-specific), for enzymes catalyzing the same reaction, but which are B-specific with respect to hydrogen transfer to/from NAD(P)+/NAD(P)H. Enzymes without information of stereospecificity are summarized under EC 1.1.1.50, but may in fact belong to EC 1.1.1.213
additional information
the enzyme belongs to the aldo-keto reductase gene family
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
binding and release or pyridine is rate-limiting
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
aldoketoreductase superfamily
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
aldoketoreductase superfamily
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
bi bi mechanism, NADP+ binds to the free enzyme before the hydroxysteroid substrate, the ketosteroid product leaves first, followed by NADPH
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
bi bi mechanism, pyridine nucleotide binds first and leaves last
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
bi bi mechanism, pyridine nucleotide binds first and leaves last
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
bi bi mechanism, pyridine nucleotide binds before substrate
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
ordered and sequential mechanism, nucleotide binds first and leaves last
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
ordered and sequential mechanism, nucleotide binds first and leaves last
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
short-chain alcohol/polyol dehydrogenase family
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
ordered bi bi reaction mechanism
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
catalytic triad residues Ser114, Tyr155, and Lys159 have mechanistic roles in the catalytic reaction
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
the enzyme reveals an 'induced-fit' mechanism involving a bound citrate ion and a conserved basic motif involved in the binding of androgen, the enzyme also binds many structurally different molecules such as 4-hydroxynonenal, polycyclic aromatic hydrocarbons, and indanone, modeling of substrate binding
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
the reduction reaction is slightly preferred by the wild-type enzyme, which is determined by residue Arg276
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
the enzyme shows a sequential ordered reaction mechanism, where NAD+ binds to the enzyme first and NADH leaves last
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
The overall oxidoreductive reaction comprises the deprotonation of tyrosine, proton abstraction by the tyrosinate anion, and hydride transfer from the hydroxysteroid to NAD+, followed by the release of a proton from the hydroxy group of tyrosine to the solution., The proton transfer to the external base, from Tyr155 to Lys159 via 2'-OH of ribose, with a late transition state is the rate-limiting step, mechanism, overview
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a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
bi bi ordered mechanism, kinetic analysis, overview
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
short-chain alcohol/polyol dehydrogenase family
-
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
bi bi mechanism, pyridine nucleotide binds before substrate
-
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
ordered and sequential mechanism, nucleotide binds first and leaves last
-
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
redox reaction
-
-
-
-
reduction
-
-
-
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oxidation
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
MetaCyc
allopregnanolone biosynthesis, backdoor pathway of androgen biosynthesis, bile acid biosynthesis, neutral pathway, testosterone and androsterone degradation to androstendione (aerobic)
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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.
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CAS REGISTRY NUMBER
COMMENTARY
9028-56-2
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(11S,12S)-11,12-dihydrobenzo[g]chrysene-11,12-diol + NADP+
? + NADPH + H+
Substrates: enzyme is stereoselective for benzo[g]chrysene-11S,12S-dihydrodiol
Products: -
Products: -
?
(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+
?
-
Substrates: -
Products: -
Products: -
r
(5beta,20R)-20-hydroxypregnan-3-one + NADH + H+
?
-
Substrates: -
Products: -
Products: -
r
(S)-alpha-tetralol + NADP+
alpha-tetralone + NADPH + H+
Substrates: -
Products: -
Products: -
?
1-acetophenone + NADPH
1-phenylethanol + NADP+
-
Substrates: -
Products: -
Products: -
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
-
Substrates: the rate of dihydrotestosterone reduction over back-conversion is 2.4 and 5.9 for prostate and epididymis, respectively
Products: -
Products: -
r
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
17beta-hydroxy-5alpha-androstan-3-one + NADPH
3alpha,17beta-dihydroxy-5alpha-androstan + NADP+
-
Substrates: -
Products: -
Products: -
r
2-acetylpyridine + NADPH
1-(2-pyridyl)ethanol + NADP+
-
Substrates: stereoselective catalysis producing mainly the (S)-alcohols
Products: -
Products: -
?
3-acetylpyridine + NADPH
1-(3-pyridyl)ethanol + NADP+
-
Substrates: low activity, stereoselective catalysis producing mainly the (S)-alcohols
Products: -
Products: -
?
3-ketosteroids + NADPH
3-hydroxysteroids + NADP+
Substrates: -
Products: -
Products: -
?
3-oxo-cholic acid + NAD(P)H + H+
cholic acid + NAD(P)+
R7B6R4
Substrates: 84.5% of the activity compared to the substrate 3-oxodeoxycholic acid
Products: -
Products: -
r
3-oxo-deoxycholic acid + NAD(P)H + H+
deoxycholic acid + NAD(P)+
R7B6R4
Substrates: -
Products: -
Products: -
r
3alpha-androstanediol + NAD+
5alpha-dihydrotestosterone + NADH + H+
-
Substrates: steroid reduction direction is preferred
Products: -
Products: -
r
3alpha-hydroxy-5alpha-androstan-17-one + NADP+
5alpha-androstan-3,17-dione + NADPH
-
Substrates: -
Products: -
Products: -
r
4-acetylpyridine + NADPH + H+
(S)-1-(4-pyridyl)ethanol + NADP+
-
Substrates: -
Products: -
Products: -
?
4-acetylpyridine + NADPH + H+
1-(4-pyridyl)ethanol + NADP+
-
Substrates: stereoselective catalysis producing mainly the (S)-alcohols
Products: -
Products: -
?
4-androsten-3alpha-ol-17-one + NADH + H+
4-androsten-3alpha,17beta-diol + NAD+
-
Substrates: AKR1C17
Products: -
Products: -
r
4-androstene-3,17-dione + NADH + H+
4-androsten-3alpha-ol-17-one + NAD+
-
Substrates: low activity
Products: -
Products: -
r
4-bromoacetophenone + NADPH + H+
1-(4-bromophenyl)ethanol + NADP+
-
Substrates: -
Products: -
Products: -
?
4-cyanoacetophenone + NADPH + H+
1-(4-cyanophenyl)ethanol + NADP+
-
Substrates: -
Products: -
Products: -
?
4-methylacetophenone + NADPH + H+
1-(4-methylphenyl)ethanol + NADP+
-
Substrates: -
Products: R,S-enantiomeric product
Products: R,S-enantiomeric product
?
4-nitroacetophenone + NAD(P)H
1-(4-nitrophenyl)ethanol + NAD(P)+
-
Substrates: pH 6.0
Products: -
Products: -
?
4-nitroacetophenone + NADPH + H+
1-(4-nitrophenyl)ethanol + NADP+
-
Substrates: -
Products: -
Products: -
?
4-oxo-2-nonenal + NADPH + H+
4-hydroxynonenal + NADP+
Substrates: -
Products: -
Products: -
?
5alpha-androstan-17beta-ol-3-one + NADPH + H+
5alpha-androstan-3alpha,17beta-diol + NADP+
-
Substrates: -
Products: -
Products: -
?
5alpha-androstane-3,17-dione + NADH
5alpha-androstan-3alpha-ol-17-one + NAD+
-
Substrates: low activity
Products: AKR1C9
Products: AKR1C9
r
5alpha-androstane-3alpha,17beta-diol + NADP+
5alpha-androstane-17beta-ol-3-one + NADPH
-
Substrates: -
Products: -
Products: -
r
5alpha-androstanedione + NADPH + H+
5alpha-androstan-3alpha-ol-17-one + NADP+
-
Substrates: -
Products: i.e. allopregnanolone
Products: i.e. allopregnanolone
?
5alpha-dihydrotestosterone + NAD(P)H + H+
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
-
Substrates: -
Products: -
Products: -
?
5alpha-dihydrotestosterone + NADH
?
-
Substrates: low activity
Products: -
Products: -
?
5alpha-pregnan-3,20-dione + NAD(P)H + H+
5alpha-pregnan-3alpha-ol-20-one + NAD(P)+
-
Substrates: regulation of the amount of allosteric agonists that can bind to the GABA receptor in brain
Products: -
Products: -
r
5alpha-pregnan-3alpha,21-diol-20-one + NADP+
5alpha-pregnan-21-ol-3,20-dione + NADPH
-
Substrates: -
Products: -
Products: -
r
5alpha-pregnane-20alpha-ol-3-one + NADH
5alpha-pregnane-3,20alpha-diol + NAD+
-
Substrates: -
Products: -
Products: -
?
5alpha-pregnane-3,20-dione + NADH
5alpha-pregnan-3alpha-ol-20-one + NAD+
-
Substrates: low activity
Products: -
Products: -
r
5beta-androstan-3alpha-ol-17-one + NAD(P)+
5beta-androstane-3,17-dione + NAD(P)H
-
Substrates: -
Products: -
Products: -
r
5beta-androstan-3alpha-ol-17-one + NADH
5beta-androstane-3alpha,17beta-diol + NAD+
-
Substrates: -
Products: -
Products: -
r
5beta-androstan-3alpha-ol-17-one + NADP+
5beta-androstan-3,17-dione + NADPH
-
Substrates: -
Products: -
Products: -
?
5beta-androstane-3,17-dione + NADH
5beta-androstan-3alpha-ol-17-one + NAD+
-
Substrates: -
Products: -
Products: -
r
5beta-androstane-3alpha,17beta-diol + NADP+
5beta-androstane-17beta-ol-3-one + NADPH
-
Substrates: -
Products: -
Products: -
r
5beta-dihydrocortisone + NADPH
3alpha,17alpha,21-trihydroxy-5beta-pregnan-11,20-dione + NADP+
-
Substrates: -
Products: -
Products: -
?
5beta-pregnan-3alpha-ol-20-one + NAD(P)+
5beta-pregnane-3,20-dione + NAD(P)H
-
Substrates: -
Products: -
Products: -
r
5beta-pregnan-3alpha-ol-20-one + NADP+
5beta-pregnane-3,20-dione + NADPH
-
Substrates: -
Products: -
Products: -
r
5beta-pregnane-17alpha,20beta,21-triol-3,11-dione + NAD(P)H
5beta-pregnane-3alpha,17alpha,20beta,21-tetraol-11-one + NAD(P)+
5beta-pregnane-20alpha-ol-3-one + NADH + H+
5beta-pregnane-3,20alpha-diol + NAD+
-
Substrates: -
Products: -
Products: -
?
5beta-pregnane-3,20-dione + NADH + H+
5beta-pregnan-3alpha-ol-20-one + NAD+
-
Substrates: -
Products: -
Products: -
r
6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one + NADH
?
-
Substrates: the enzyme produces both R- and S-form products in a ratio of 2.3 : 1
Products: -
Products: -
?
7alpha,12alpha-dihydroxy-5beta-cholestan-3-one + NADPH + H+
5beta-cholestane-3alpha,7alpha,12alpha-triol + NADP+
-
Substrates: -
Products: -
Products: -
?
7alpha-hydroxy-5beta-cholestan-3-one + NADPH + H+
5beta-cholestane-3alpha,7alpha-diol + NADP+
-
Substrates: -
Products: -
Products: -
?
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+
acetophenone + NADPH + H+
1-phenylethanol + NADP+
-
Substrates: -
Products: -
Products: -
?
androstan-17beta-ol-3-one + NADH
androstan-3alpha,17beta-diol + NAD+
-
Substrates: -
Products: -
Products: -
?
androstan-3,17-dione + NADH
androstan-3alpha-ol-17-one + NAD+
-
Substrates: -
Products: -
Products: -
?
androsterone + NAD(P)+
5alpha-androstane-3,17-dione + NAD(P)H
-
Substrates: -
Products: -
Products: -
r
androsterone + NAD+
5alpha-androstane-3,17-dione + NADH
-
Substrates: -
Products: -
Products: -
r
androsterone + NADP+
5alpha-androstane-3,17-dione + NADPH
-
Substrates: -
Products: -
Products: -
r
benzo[c]phenanthrene-3,4-dihydrodiol + NADP+
? + NADPH + H+
Substrates: enzyme metabolizes both stereoisomers of benzo[c]phenanthrene-3,4-dihydrodiol
Products: -
Products: -
?
chenodeoxycholic acid + NAD(P)+
3-oxo-chenodeoxycholic acid + NAD(P)H + H+
R7B6R4
Substrates: 19.8% of the activity compared to the substrate 3-oxodeoxycholic acid
Products: -
Products: -
r
cholic acid + NAD(P)+
3-oxo-cholic acid + NAD(P)H + H+
R7B6R4
Substrates: 65.5% of the activity compared to the substrate 3-oxodeoxycholic acid
Products: -
Products: -
r
deoxycholic acid + NAD(P)+
3-oxo-deoxycholic acid + NAD(P)H + H+
R7B6R4
Substrates: 71.7% of the activity compared to the substrate 3-oxodeoxycholic acid
Products: -
Products: -
r
etiocholane-3,17-dione + NADH
etiocholan-3alpha-ol-17-one + NAD+
-
Substrates: -
Products: -
Products: -
?
glycochenodeoxycholic acid + NAD(P)+
? + NAD(P)H + H+
R7B6R4
Substrates: 50.7% of the activity compared to the substrate 3-oxodeoxycholic acid
Products: -
Products: -
r
glycochenodeoxycholic acid + NADP+
7alpha-hydroxy-3-oxo-5beta-cholanoyl glycine + NADPH
-
Substrates: -
Products: -
Products: -
?
glycocholic acid + NAD(P)+
? + NAD(P)H + H+
R7B6R4
Substrates: 61.2% of the activity compared to the substrate 3-oxodeoxycholic acid
Products: -
Products: -
r
glycodeoxycholic acid + NAD(P)+
? + NAD(P)H + H+
R7B6R4
Substrates: 57.8% of the activity compared to the substrate 3-oxodeoxycholic acid
Products: -
Products: -
r
glycolithocholic acid + NADP+
3-oxo-5beta-cholanoyl glycine + NADPH
-
Substrates: -
Products: -
Products: -
?
lithocholic acid + NADP+
dehydrolithocholic acid + NADPH
-
Substrates: -
Products: -
Products: -
r
pregnane-11beta,17alpha,21-triol-3,20-dione + NADH
pregnane-3alpha,11beta,17alpha,21-tetrol-20-one + NAD+
-
Substrates: -
Products: -
Products: -
?
progesterone + NAD(P)H
3alpha-hydroxy-pregn-4-ene-20-one + NAD(P)+
-
Substrates: -
Products: -
Products: -
r
prostaglandin + NADP+
? + NADPH
-
Substrates: types A1, A2, B1, B2, D2, E1, E2, F1, F2alpha and 15-keto-prostaglandinE2 and F2alpha
Products: -
Products: -
?
prostaglandin-F2alpha + NADP+
prostaglandin F2 + prostaglandin B2 + NADPH
-
Substrates: -
Products: -
Products: -
?
taurochenodeoxycholic acid + NAD(P)+
? + NAD(P)H + H+
R7B6R4
Substrates: 53.3% of the activity compared to the substrate 3-oxodeoxycholic acid
Products: -
Products: -
r
taurocholic acid + NAD(P)+
? + NAD(P)H + H+
R7B6R4
Substrates: 63.9% of the activity compared to the substrate 3-oxodeoxycholic acid
Products: -
Products: -
r
taurodeoxychloic acid + NAD(P)+
? + NAD(P)H + H+
R7B6R4
Substrates: 59.2% of the activity compared to the substrate 3-oxodeoxycholic acid
Products: -
Products: -
r
testosterone + NAD(P)H + H+
4-androsten-3alpha,17beta-diol + NAD(P)+
-
Substrates: -
Products: -
Products: -
r
1-(4'nitrophenyl)prop-2-en-1-ol + NAD+
1-(4'nitrophenyl)prop-2-en-1-one + NADH
-
Substrates: -
Products: -
Products: -
?
1-(4'nitrophenyl)prop-2-en-1-ol + NAD+
1-(4'nitrophenyl)prop-2-en-1-one + NADH
-
Substrates: -
Products: -
Products: -
?
1-(4'nitrophenyl)prop-2-yn-1-ol + NAD+
1-(4'nitrophenyl)prop-2-yn-1-one + NADH
-
Substrates: -
Products: -
Products: -
?
1-(4'nitrophenyl)prop-2-yn-1-ol + NAD+
1-(4'nitrophenyl)prop-2-yn-1-one + NADH
-
Substrates: -
Products: -
Products: -
?
1-acenaphthenol + NAD(P)+
1-acenaphthenone + NAD(P)H + H+
-
Substrates: pH 9.0
Products: -
Products: -
?
1-acenaphthenol + NAD(P)+
1-acenaphthenone + NAD(P)H + H+
-
Substrates: pH 9.0
Products: -
Products: -
?
10-oxonortriptyline + NADPH
?
Substrates: a drug acting as substrate
Products: -
Products: -
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
-
Substrates: -
Products: -
Products: -
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
Substrates: -
Products: -
Products: -
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
-
Substrates: termination of androgen action
Products: -
Products: -
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
-
Substrates: conversion in animal tissues
Products: -
Products: -
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
-
Substrates: regulation of the amount of androgen in prostate, high levels of substrate are required for normal and abnormal growth of prostate
Products: -
Products: -
r
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
-
Substrates: termination of androgen action
Products: -
Products: -
?
2 tibolone + 2 NADPH + 2 H+
3alpha-hydroxytibolone + 3beta-hydroxytibolone + 2 NADP+
Substrates: 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
Products: 3alpha-hydroxytibolone is the primary metabolite
Products: 3alpha-hydroxytibolone is the primary metabolite
r
2 tibolone + 2 NADPH + 2 H+
3alpha-hydroxytibolone + 3beta-hydroxytibolone + 2 NADP+
Substrates: i.e. tibolone, a 3-ketosteroid androgen receptor, conversion to potent estrogen receptor alpha agonists, overview
Products: 3alpha-hydroxytibolone is the primary metabolite
Products: 3alpha-hydroxytibolone is the primary metabolite
r
3alpha,5alpha-allopregnenolone + NAD(P)+
5alpha-dihydroprogesterone + NAD(P)H
-
Substrates: 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
Products: -
Products: -
r
3alpha,5alpha-allopregnenolone + NAD(P)+
5alpha-dihydroprogesterone + NAD(P)H
-
Substrates: i.e. 3alpha,5alpha-tetrahydroprogesterone or 3alpha,5alpha-THP
Products: -
Products: -
r
3alpha-hydroxy-5alpha-androstan-17-one + NAD+
5alpha-androstan-3,17-dione + NADH
-
Substrates: -
Products: -
Products: -
r
3alpha-hydroxy-5alpha-androstan-17-one + NAD+
5alpha-androstan-3,17-dione + NADH
-
Substrates: pH 9.0
Products: -
Products: -
?
3alpha-hydroxy-5alpha-androstan-17-one + NAD+
5alpha-androstan-3,17-dione + NADH
-
Substrates: pH 9.0
Products: -
Products: -
?
4'-methoxyacetophenone + NADPH + H+
1-(4-methoxyphenyl)ethanol + NADP+
-
Substrates: -
Products: -
Products: -
?
4'-methoxyacetophenone + NADPH + H+
1-(4-methoxyphenyl)ethanol + NADP+
-
Substrates: -
Products: R,S-enantiomeric product
Products: R,S-enantiomeric product
?
4-nitrobenzaldehyde + NAD(P)H
(4-nitrophenyl)methanol + NAD(P)+
-
Substrates: pH 6.0
Products: -
Products: -
?
4-nitrobenzaldehyde + NAD(P)H
(4-nitrophenyl)methanol + NAD(P)+
-
Substrates: NADH as cofactor
Products: -
Products: -
?
5alpha-androstan-3,17-dione + NAD(P)H
3alpha-hydroxy-5alpha-androstan-17-one + NAD(P)+
Substrates: -
Products: -
Products: -
r
5alpha-androstan-3,17-dione + NAD(P)H
3alpha-hydroxy-5alpha-androstan-17-one + NAD(P)+
-
Substrates: pH 6.0 for reduction, pH 7.0 and 9.0 for androsterone oxidation
Products: -
Products: -
r
5alpha-androstan-3,17-dione + NAD(P)H
3alpha-hydroxy-5alpha-androstan-17-one + NAD(P)+
-
Substrates: pH 6.0 for reduction, pH 7.0 and 9.0 for androsterone oxidation
Products: -
Products: -
r
5alpha-androstan-3alpha-ol-17-one + NADH + H+
5beta-androstan-3alpha,17beta-diol + NAD+
-
Substrates: -
Products: -
Products: -
?
5alpha-androstan-3alpha-ol-17-one + NADH + H+
5beta-androstan-3alpha,17beta-diol + NAD+
-
Substrates: -
Products: -
Products: -
r
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
Substrates: the enzyme plays a crucial role in the regulation of the intracellular concentrations of testosterone and 5alpha-dihydrotestosterone, two steroids directly linked to the etiology and the progression of many prostate diseases and cancer, overview
Products: -
Products: -
r
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
Substrates: the enzyme is important in inactivation of DHT
Products: -
Products: -
?
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
Substrates: androgen-inactivating enzyme
Products: -
Products: -
r
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
Substrates: i.e. DHT, substrate and cofactor binding site structure
Products: -
Products: -
r
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
Substrates: i.e. DHT
Products: -
Products: -
?
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
Substrates: i.e. DHT, the enzyme prefers the reductive reaction
Products: -
Products: -
r
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
-
Substrates: i.e. DHT
Products: -
Products: -
?
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
-
Substrates: -
Products: -
Products: -
?
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
-
Substrates: i.e. DHT or 5alpha-androstane-17beta-ol-3-one, the reduction reaction is slightly preferred by the wild-type enzyme, which is determined by residue Arg276
Products: i.e. 5alpha-androstane-3alpha,17beta-diol
Products: i.e. 5alpha-androstane-3alpha,17beta-diol
?
5alpha-dihydrotestosterone + NADPH + H+
3alpha-androstanediol + NADP+
-
Substrates: steroid reduction direction is preferred
Products: -
Products: -
r
5alpha-dihydrotestosterone + NADPH + H+
3alpha-androstanediol + NADP+
-
Substrates: the chemical oxidation step is rate-limiting, W227 is very important for cataylsis, steroid reduction direction is preferred
Products: -
Products: -
r
5alpha-dihydrotestosterone + NADPH + H+
5alpha-androstan-3alpha,17beta-diol + NADP+
-
Substrates: inactivation of the potent androgen in human prostate
Products: -
Products: -
r
5alpha-dihydrotestosterone + NADPH + H+
5alpha-androstan-3alpha,17beta-diol + NADP+
-
Substrates: inactivation of the potent androgen in human prostate, fluorometric activity measurement in intact cells, overview
Products: -
Products: -
?
5alpha-dihydrotestosterone + NADPH + H+
5alpha-androstan-3alpha,17beta-diol + NADP+
-
Substrates: i.e. DHT
Products: -
Products: -
r
5alpha-dihydrotestosterone + NADPH + H+
5alpha-androstan-3alpha,17beta-diol + NADP+
-
Substrates: i.e. DHT
Products: -
Products: -
?
5beta-pregnane-17alpha,20beta,21-triol-3,11-dione + NAD(P)H
5beta-pregnane-3alpha,17alpha,20beta,21-tetraol-11-one + NAD(P)+
-
Substrates: -
Products: -
Products: -
r
5beta-pregnane-17alpha,20beta,21-triol-3,11-dione + NAD(P)H
5beta-pregnane-3alpha,17alpha,20beta,21-tetraol-11-one + NAD(P)+
-
Substrates: hepatic reduction in animal tissues
Products: -
Products: -
?
9,10-phenanthrenequinone + NAD(P)H
? + NAD(P)+
-
Substrates: NADPH
Products: -
Products: -
?
9,10-phenanthrenequinone + NAD(P)H
? + NAD(P)+
-
Substrates: pH 6.0
Products: -
Products: -
?
9,10-phenanthrenequinone + NAD(P)H
? + NAD(P)+
-
Substrates: pH 6.0
Products: -
Products: -
?
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+
-
Substrates: competitive substrate, fluorometric activity measurement in intact cells, overview
Products: -
Products: -
?
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+
-
Substrates: competitive substrate
Products: -
Products: -
?
acetohexamide + NADPH
?
Substrates: a drug acting as substrate
Products: -
Products: -
?
androsterone + NAD+
androstanedione + NADH
-
Substrates: -
Products: -
Products: -
r
androsterone + NAD+
androstanedione + NADH
-
Substrates: the intramolecular proton transfer is a rate-limiting step, with a concomitant releasing of protons to bulk solvent
Products: -
Products: -
r
benzenedihydrodiol + NAD(P)+
?
-
Substrates: pH 9.0
Products: -
Products: -
?
cholic acid + NAD(P)+
3-oxocholate + NAD(P)H
-
Substrates: -
Products: very little activity
Products: very little activity
?
cholic acid + NAD(P)+
3-oxocholate + NAD(P)H
-
Substrates: -
Products: very little activity
Products: very little activity
?
choloyl-CoA + NAD(P)+
3-oxocholoyl-CoA + NAD(P)H + H+
-
Substrates: -
Products: -
Products: -
r
choloyl-CoA + NAD(P)+
3-oxocholoyl-CoA + NAD(P)H + H+
-
Substrates: -
Products: -
Products: -
r
daunorubicin + NADPH
?
Substrates: a drug acting as substrate
Products: -
Products: -
?
deoxycholoyl-CoA + NAD(P)+
3-oxodeoxycholoyl-CoA + NAD(P)H + H+
-
Substrates: 75% activity compared with cholyl-CoA
Products: -
Products: -
?
deoxycholoyl-CoA + NAD(P)+
3-oxodeoxycholoyl-CoA + NAD(P)H + H+
-
Substrates: 75% activity compared with cholyl-CoA
Products: -
Products: -
?
dolasetron + NADPH
?
Substrates: a drug acting as substrate
Products: -
Products: -
?
haloperidol + NADPH
?
Substrates: a drug acting as substrate
Products: -
Products: -
?
ketoprofen + NADPH
?
Substrates: a drug acting as substrate
Products: -
Products: -
?
loxoprofen + NADPH
?
Substrates: a drug acting as substrate
Products: -
Products: -
?
Naltrexone + NADPH
?
Substrates: a drug acting as substrate
Products: -
Products: -
?
tibolone + NADPH + H+
3-hydroxytibolone + NADP+
-
Substrates: 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
Products: -
Products: -
?
tibolone + NADPH + H+
3-hydroxytibolone + NADP+
-
Substrates: i.e. [7alpha,17alpha]-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one, stereoselctive reaction to the 3alpha-hydroxytibolone product
Products: -
Products: -
?
additional information
?
-
-
Substrates: bifunctional enzyme exhibiting 3alpha-hydroxysteroid dehydrogenase activity and carbonyl reductase activity
Products: -
Products: -
?
additional information
?
-
R7B6R4
Substrates: no activity with isodeoxycholic acid
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity with cholate, chenodeoxycholate, deoxycholate, glycocholate, taurocholate, ursodeoxycholate and bile acid
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity with cholate, chenodeoxycholate, deoxycholate, glycocholate, taurocholate, ursodeoxycholate and bile acid
Products: -
Products: -
?
additional information
?
-
Substrates: the enzyme is important in the synthesis of neuroactive 5alpha/beta-pregnan-3alpha-ol-20-ones from their precursors, the enzyme plays a role in development and progression of prostate cancer
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme is important in the synthesis of neuroactive 5alpha/beta-pregnan-3alpha-ol-20-ones from their precursors, the enzyme plays a role in development and progression of prostate cancer
Products: -
Products: -
?
additional information
?
-
Substrates: the RODH like 3alpha/17beta-HSD, EC 1.1.1.239, regulates the transactivation of AKR1C2, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: the RODH like 3alpha/17beta-HSD, EC 1.1.1.239, regulates the transactivation of AKR1C2, overview
Products: -
Products: -
?
additional information
?
-
Substrates: besides 3alpha-hydroxysteroid dehydrogenase activity, the enzyme shows also 17beta-hydroxysteroid dehydrogenase activity towards 5alpha-dihydrotestosterone, EC 1.1.1.239, overview, the enzyme reveals an 'induced-fit' mechanism and a conserved basic motif involved in the binding of androgen, the enzyme also binds many structurally different molecules such as 4-hydroxynonenal, polycyclic aromatic hydrocarbons, and indanone
Products: -
Products: -
?
additional information
?
-
-
Substrates: besides 3alpha-hydroxysteroid dehydrogenase activity, the enzyme shows also 17beta-hydroxysteroid dehydrogenase activity towards 5alpha-dihydrotestosterone, EC 1.1.1.239, overview, the enzyme reveals an 'induced-fit' mechanism and a conserved basic motif involved in the binding of androgen, the enzyme also binds many structurally different molecules such as 4-hydroxynonenal, polycyclic aromatic hydrocarbons, and indanone
Products: -
Products: -
?
additional information
?
-
-
Substrates: AKR1C3 catalyzes androgen, estrogen, and prostaglandin metabolism, AKR1C3 is also involved in cancer development or progression
Products: -
Products: -
?
additional information
?
-
-
Substrates: an androgen-inactivating enzyme, important in androgen and progesterone metabolism
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme might play an important role in female physiology, substrate specificity, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: metabolizes androgens and glucocorticoids, function as a dihydrodiol dehydrogenase as well as 9-, 11-, and 15-hydroxyprostaglandin dehydrogenase, enzyme catalyzes both oxidation and reduction reaction at physiological pH and is able to reduce aromatic ketones
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme displays a distinct preference for the reduction of quinones, e.g. 9,10-phenanthrenequinone, and 3-oxo steroids, e.g. androstane, pregnane and cholane, over aromatic aldehydes and ketones, whereas 3alpha-hydroxy steroids are overwhelmingly more efficiently oxidized than are 1-acenaphthenol or benzenedihydrodiol. Ethanol and 3beta-hydroxy steroids no substrates
Products: -
Products: -
?
additional information
?
-
-
Substrates: oxidation of 3alpha-hydroxysteroids, secondary alcohols and trans-dihydrodiol proximate carcinogens derived from polycyclic aromatic hydrocarbons, reduction of quinones, aromatic aldehydes and ketones, 9-, 11-, and 15-hydroxyprostaglandin dehydrogenase activity of enzyme
Products: -
Products: -
?
additional information
?
-
Substrates: biosynthesis and inactivation of steroid hormones, physiological role is to inactivate circulating androgens, progestins and glucocorticoids
Products: -
Products: -
?
additional information
?
-
-
Substrates: involved in biosynthesis of bile acids
Products: -
Products: -
?
additional information
?
-
-
Substrates: inactivating circulating androgens, progestins and glucocorticoids. Regulation of hormone levels in endocrine target tissues and in carcinogen actibation
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity with acetylpyrroles
Products: -
Products: -
?
additional information
?
-
Substrates: C/EBPdelta regulates the AKR1C9 gene promoter in osteoblasts, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: AKR1C9 catalyzes androgen, estrogen, and prostaglandin metabolism
Products: -
Products: -
?
additional information
?
-
-
Substrates: substrate specificty, overview, recombinant AKR1C17 efficiently oxidizes 3alpha-hydroxysteroids and diverse bile acids using NAD+ as the preferred coenzyme, no activity with progesterone, cortisone, and aldosterone. The enzyme also reduces non-steroidal alpha-dicarbonyl compounds such as 9,10-phenanethrenequinone, isatin, 6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one and diacetyl, but does not show significant activities towards 4-nitrobenzaldehyde and 4-nitroacetophenone
Products: -
Products: -
?
additional information
?
-
-
Substrates: acetophenone derivatives are reduced enantioselectively by rat liver 3alpha-HSD to give (S)-alcohols
Products: -
Products: -
?
additional information
?
-
-
Substrates: metabolizes androgens and glucocorticoids, function as a dihydrodiol dehydrogenase as well as 9-, 11-, and 15-hydroxyprostaglandin dehydrogenase, enzyme catalyzes both oxidation and reduction reaction at physiological pH and is able to reduce aromatic ketones
Products: -
Products: -
?
additional information
?
-
-
Substrates: involved in biosynthesis of bile acids
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
10-oxonortriptyline + NADPH
?
Substrates: a drug acting as substrate
Products: -
Products: -
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
2 tibolone + 2 NADPH + 2 H+
3alpha-hydroxytibolone + 3beta-hydroxytibolone + 2 NADP+
Substrates: 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
Products: 3alpha-hydroxytibolone is the primary metabolite
Products: 3alpha-hydroxytibolone is the primary metabolite
r
3-ketosteroids + NADPH
3-hydroxysteroids + NADP+
Substrates: -
Products: -
Products: -
?
3alpha,5alpha-allopregnenolone + NAD(P)+
5alpha-dihydroprogesterone + NAD(P)H
-
Substrates: 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
Products: -
Products: -
r
3alpha-androstanediol + NAD+
5alpha-dihydrotestosterone + NADH + H+
-
Substrates: steroid reduction direction is preferred
Products: -
Products: -
r
4-acetylpyridine + NADPH + H+
(S)-1-(4-pyridyl)ethanol + NADP+
-
Substrates: -
Products: -
Products: -
?
5alpha-dihydrotestosterone + NAD(P)H + H+
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
-
Substrates: -
Products: -
Products: -
?
5alpha-dihydrotestosterone + NADPH + H+
3alpha-androstanediol + NADP+
-
Substrates: steroid reduction direction is preferred
Products: -
Products: -
r
5alpha-pregnan-3,20-dione + NAD(P)H + H+
5alpha-pregnan-3alpha-ol-20-one + NAD(P)+
-
Substrates: regulation of the amount of allosteric agonists that can bind to the GABA receptor in brain
Products: -
Products: -
r
5beta-pregnane-17alpha,20beta,21-triol-3,11-dione + NAD(P)H
5beta-pregnane-3alpha,17alpha,20beta,21-tetraol-11-one + NAD(P)+
-
Substrates: hepatic reduction in animal tissues
Products: -
Products: -
?
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+
-
Substrates: competitive substrate, fluorometric activity measurement in intact cells, overview
Products: -
Products: -
?
acetohexamide + NADPH
?
Substrates: a drug acting as substrate
Products: -
Products: -
?
acetophenone + NADPH + H+
1-phenylethanol + NADP+
-
Substrates: -
Products: -
Products: -
?
androsterone + NAD+
5alpha-androstane-3,17-dione + NADH
-
Substrates: -
Products: -
Products: -
r
androsterone + NAD+
androstanedione + NADH
-
Substrates: -
Products: -
Products: -
r
androsterone + NADP+
5alpha-androstane-3,17-dione + NADPH
-
Substrates: -
Products: -
Products: -
r
daunorubicin + NADPH
?
Substrates: a drug acting as substrate
Products: -
Products: -
?
dolasetron + NADPH
?
Substrates: a drug acting as substrate
Products: -
Products: -
?
haloperidol + NADPH
?
Substrates: a drug acting as substrate
Products: -
Products: -
?
ketoprofen + NADPH
?
Substrates: a drug acting as substrate
Products: -
Products: -
?
loxoprofen + NADPH
?
Substrates: a drug acting as substrate
Products: -
Products: -
?
Naltrexone + NADPH
?
Substrates: a drug acting as substrate
Products: -
Products: -
?
tibolone + NADPH + H+
3-hydroxytibolone + NADP+
-
Substrates: 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
Products: -
Products: -
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
-
Substrates: -
Products: -
Products: -
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
Substrates: -
Products: -
Products: -
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
-
Substrates: termination of androgen action
Products: -
Products: -
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
-
Substrates: conversion in animal tissues
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17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
-
Substrates: regulation of the amount of androgen in prostate, high levels of substrate are required for normal and abnormal growth of prostate
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r
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
-
Substrates: termination of androgen action
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5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
Substrates: the enzyme plays a crucial role in the regulation of the intracellular concentrations of testosterone and 5alpha-dihydrotestosterone, two steroids directly linked to the etiology and the progression of many prostate diseases and cancer, overview
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r
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
Substrates: the enzyme is important in inactivation of DHT
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?
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
Substrates: androgen-inactivating enzyme
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r
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
-
Substrates: -
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5alpha-dihydrotestosterone + NADPH + H+
5alpha-androstan-3alpha,17beta-diol + NADP+
-
Substrates: inactivation of the potent androgen in human prostate
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r
5alpha-dihydrotestosterone + NADPH + H+
5alpha-androstan-3alpha,17beta-diol + NADP+
-
Substrates: inactivation of the potent androgen in human prostate, fluorometric activity measurement in intact cells, overview
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additional information
?
-
Substrates: the enzyme is important in the synthesis of neuroactive 5alpha/beta-pregnan-3alpha-ol-20-ones from their precursors, the enzyme plays a role in development and progression of prostate cancer
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additional information
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-
-
Substrates: the enzyme is important in the synthesis of neuroactive 5alpha/beta-pregnan-3alpha-ol-20-ones from their precursors, the enzyme plays a role in development and progression of prostate cancer
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additional information
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-
Substrates: the RODH like 3alpha/17beta-HSD, EC 1.1.1.239, regulates the transactivation of AKR1C2, overview
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additional information
?
-
-
Substrates: the RODH like 3alpha/17beta-HSD, EC 1.1.1.239, regulates the transactivation of AKR1C2, overview
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additional information
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-
-
Substrates: AKR1C3 catalyzes androgen, estrogen, and prostaglandin metabolism, AKR1C3 is also involved in cancer development or progression
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additional information
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-
-
Substrates: an androgen-inactivating enzyme, important in androgen and progesterone metabolism
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additional information
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-
Substrates: biosynthesis and inactivation of steroid hormones, physiological role is to inactivate circulating androgens, progestins and glucocorticoids
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additional information
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-
-
Substrates: involved in biosynthesis of bile acids
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additional information
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-
-
Substrates: inactivating circulating androgens, progestins and glucocorticoids. Regulation of hormone levels in endocrine target tissues and in carcinogen actibation
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additional information
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Substrates: C/EBPdelta regulates the AKR1C9 gene promoter in osteoblasts, overview
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additional information
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-
-
Substrates: AKR1C9 catalyzes androgen, estrogen, and prostaglandin metabolism
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additional information
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-
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Substrates: involved in biosynthesis of bile acids
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NAD+
-
preferred by AKR1C17, dependent on, residues Gln270 and Glu276 are important for cofactor specificity, overview
NADH
-
A-specific, hydride transfer occurs from the 4-pro-R-position of the cofactor to the C-3 position of the steroid
NADP+
-
preferred by AKR1C9, dependent on, residues Gln270 and Glu276 are important for cofactor specificity, overview
NADP+
-
loose association of the NADP(H) is followed by two conformational changes, which increases cofactor affinity by 86fold
NADPH
-
pro-R-hydrogen atom is transferred to the carbonyl substrate, A-specific
NADPH
-
loose association of the NADP(H) is followed by two conformational changes, which increases cofactor affinity by 86fold
additional information
-
dual pyridine nucleotide specificity, cofactor binding-site is located at the NH2 terminus
-
additional information
-
for a number of substrates the reactions are more efficient in the presence of NADPH and NADP+
-
additional information
-
4-pro-(R) hydrogen is transferred from the A-face of the cofactor to the B-face of the steroid
-
additional information
-
4-pro-R-hydride transfer of the nicotinamide cofactor
-
additional information
transfer of the 4-pro-R hydrogen from A-face of cofactor to the beta-face of the steroid substrate. Different binding modes for NAD(H) and NADP(H)
-
additional information
-
R276 plays an important role in cofactor binding
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
citrate
bound to the steroid-binding cavity via Tyr55 and His117, involved in the induced fit mechanism
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INHIBITOR
ORGANISM
UNIPROT
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
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
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
17beta-bromoacetoxy-5alpha-dihydrotestosterone
-
inactivation by modification of steroid-binding site
2'-hydroxyflavanone
-
most potent inhibitor, 0.02 mM inhibits by 98.9% and in an uncompetitive manner
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
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
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
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
9-(phenylcarbonyl)-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one
-
competitive
acetylenic ketones
-
inactivation by forming Michael adducts with enzyme nucleophiles
-
celecoxib
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.050 mM in fluorometric assay, in vitro IC50: 0.050 mM in fluorometric assay
Cibacron blue
-
nucleotide analog, competitive with respect to NADP+, noncompetitive to androsterone
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
naphthalene-1,2-dione
naphthalene-1,2-dione leads to the time and concentration dependent irreversible inactivation of AKR1C9 via alkylation
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
Phenolphthalein
-
AKR1C4-selective inhibitor, in vitro and in vivo inhibition, IC50: 0.0004 mM
ursodeoxycholate
-
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
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
Flufenamic acid
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.0040 mM in fluorometric assay, in vitro IC50: 0.00031 mM in fluorometric assay
Hexestrol
-
hydroxysteroid analog, uncompetitive versus NADP+, competitive versus androsterone
Ibuprofen
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.017 mM in fluorometric assay, in vitro IC50: 0.009 mM in fluorometric assay
indomethacin
-
non-steroidal anti-inflamatory drug, uncompetitive against NAD+, competitive against androsterone
indomethacin
-
competitive, IC50 for reduction of 9,10-phenanthrenequinone is 0.000735 mM and of androsterone 0.00333 mM
p-chloromercuribenzoate
-
non-competitive with respect to dihydrocortisone 46-100% inhibition at 0.01 mM, preincubation with NADH lowers the inhibitory effect
Prostaglandin
-
A1, B1, E1, F1, F1alpha, A2, B2, E2 and F2alpha, inhibit 9,10-phenanthrenequinone reduction and androsterone oxidation, the order of inhibitory potency is related to their lipophilicity
additional information
-
no inhibition by the bile acid 5beta-cholanic acid-3alpha,7alpha-diol
-
additional information
-
dutasteride alters the expression level of the enzyme in breast cancer cells, the inhibitor affects the 5alpha-progesterone reductase and the progesterone metabolism, overview
-
additional information
-
is not inhibited by 0.02 mM caffeic acid, rutin, 4-hydroxybenzoic acid, cyanin chloride and taxifolin
-
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
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-butyl-3-methylimidazolium L-lactate
-
enhanced activity of 3alpha-hydroxysteroid dehydrogenase by addition of the co-solvent to 50 mM Tris-HCl buffer in aqueous phase of biphasic systems for reductive production of steroids. In a coupled-enzyme system comprising HSDH and formate dehydrogenase, a twofold increase in production rate of androsterone is obtained when utilizing 1-butyl-3-methylimidazolium L-lactate with NADH regeneration, overview
1-ethyl-3-methylimidazolium trifluoromethanesulfonate
-
addition of the co-solvent leads to slightly enhanced enzyme activity n an aqueous-organic solvent system with Tris-HCl buffer, overview
additional information
-
poor activation by 1-butyl-3-methylimidazolium trifluoromethanesulfonate and 1-butyl-3-methylimidazolium tetrafluoroborate
-
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
-
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Adenocarcinoma
Expression of dihydrodiol dehydrogenase and resistance to chemotherapy and radiotherapy in adenocarcinoma cells of lung.
Adenocarcinoma
[Gene expression profiling of human ovarian epithelial tumors by digo nucleotide microarray]
Breast Neoplasms
An indomethacin analogue, N-(4-chlorobenzoyl)-melatonin, is a selective inhibitor of aldo-keto reductase 1C3 (type 2 3alpha-HSD, type 5 17beta-HSD, and prostaglandin F synthase), a potential target for the treatment of hormone dependent and hormone independent malignancies.
Breast Neoplasms
Selective loss of AKR1C1 and AKR1C2 in breast cancer and their potential effect on progesterone signaling.
Carcinoma
Dihydrodiol dehydrogenase in drug resistance and sensitivity of human carcinomas.
Carcinoma
Expression and characterization of recombinant type 2 3 alpha-hydroxysteroid dehydrogenase (HSD) from human prostate: demonstration of bifunctional 3 alpha/17 beta-HSD activity and cellular distribution.
Carcinoma
Expression of dihydrodiol dehydrogenase plays important roles in apoptosis- and drug-resistance of A431 squamous cell carcinoma.
Carcinoma
Increased expression of dihydrodiol dehydrogenase induces resistance to cisplatin in human ovarian carcinoma cells.
Carcinoma
Inverse expression of dihydrodiol dehydrogenase and glutathione-S-transferase in patients with esophageal squamous cell carcinoma.
Carcinoma
Sequence of the cDNA of a human dihydrodiol dehydrogenase isoform (AKR1C2) and tissue distribution of its mRNA.
Carcinoma
Ubiquitous induction of resistance to platinum drugs in human ovarian, cervical, germ-cell and lung carcinoma tumor cells overexpressing isoforms 1 and 2 of dihydrodiol dehydrogenase.
Carcinoma
[Gene expression profiling of human ovarian epithelial tumors by digo nucleotide microarray]
Carcinoma, Hepatocellular
Characterization of dihydrodiol dehydrogenase in rat H-4IIe hepatoma cells.
Carcinoma, Hepatocellular
Proteome analysis of rat hepatomas: carcinogen-dependent tumor-associated protein variants.
Carcinoma, Hepatocellular
Reduction of dihydrodiol dehydrogenase expression in resected hepatocellular carcinoma.
Carcinoma, Non-Small-Cell Lung
Expression of dihydrodiol dehydrogenase in the resected stage I non-small cell lung cancer.
Carcinoma, Non-Small-Cell Lung
Overexpression of dihydrodiol dehydrogenase as a prognostic marker of non-small cell lung cancer.
Carcinoma, Non-Small-Cell Lung
Proteomics-based identification of secreted protein dihydrodiol dehydrogenase as a novel serum markers of non-small cell lung cancer.
Carcinoma, Squamous Cell
Expression of dihydrodiol dehydrogenase plays important roles in apoptosis- and drug-resistance of A431 squamous cell carcinoma.
Colorectal Neoplasms
The long variant of human ileal bile acid-binding protein associated with colorectal cancer exhibits sub-cellular localization and lipid binding behaviour distinct from those of the common isoform.
Dupuytren Contracture
Common Variants of the ALDH2 and DHDH Genes and the Risk of Dupuytren's Disease.
Epilepsy
Characterization of the 5alpha-reductase-3alpha-hydroxysteroid dehydrogenase complex in the human brain.
Esophageal Squamous Cell Carcinoma
Inverse expression of dihydrodiol dehydrogenase and glutathione-S-transferase in patients with esophageal squamous cell carcinoma.
Glaucoma
Altered expression of 3 alpha-hydroxysteroid dehydrogenases in human glaucomatous optic nerve head astrocytes.
Hepatoblastoma
Hepatocyte nuclear factor (HNF)-4 alpha/gamma, HNF-1 alpha, and vHNF-1 regulate the cell-specific expression of the human dihydrodiol dehydrogenase (DD)4/AKR1C4 gene.
Hirsutism
3{alpha}-Hydroxysteroid Dehydrogenase Type III Deficiency: A Novel Mechanism for Hirsutism.
Hypercholesterolemia
Identification of a novel hypocholesterolemic protein, major royal jelly protein 1, derived from royal jelly.
Hyperglycemia
Pathogenesis of diabetic neuropathy--do hyperglycemia and aldose reductase inhibitors affect neuroactive steroid formation in the rat sciatic nerves?
Infections
Infection of human papillomavirus and overexpression of dihydrodiol dehydrogenase in uterine cervical cancer.
Lung Neoplasms
A possible role for dihydrodiol dehydrogenase in the formation of benzo[a]pyrene-DNA adducts in lung cancer cells and tumor tissues.
Lung Neoplasms
Diagnostic value of serum dihydrodiol dehydrogenase 2 levels in patients with non-small-cell lung cancer.
Lung Neoplasms
Expression of dihydrodiol dehydrogenase in the resected stage I non-small cell lung cancer.
Lung Neoplasms
Overexpression of dihydrodiol dehydrogenase as a prognostic marker of non-small cell lung cancer.
Lung Neoplasms
Proteomics-based identification of secreted protein dihydrodiol dehydrogenase as a novel serum markers of non-small cell lung cancer.
Neoplasm Metastasis
Extracts of Koelreuteria henryi Dummer induce apoptosis and autophagy by inhibiting dihydrodiol dehydrogenase, thus enhancing anticancer effects.
Neoplasm Metastasis
Hepatocyte growth factor and HER2/neu downregulate expression of apoptosis-inducing factor in non-small cell lung cancer.
Neoplasms
A possible role for dihydrodiol dehydrogenase in the formation of benzo[a]pyrene-DNA adducts in lung cancer cells and tumor tissues.
Neoplasms
An indomethacin analogue, N-(4-chlorobenzoyl)-melatonin, is a selective inhibitor of aldo-keto reductase 1C3 (type 2 3alpha-HSD, type 5 17beta-HSD, and prostaglandin F synthase), a potential target for the treatment of hormone dependent and hormone independent malignancies.
Neoplasms
Dihydrodiol dehydrogenases regulate the generation of reactive oxygen species and the development of cisplatin resistance in human ovarian carcinoma cells.
Neoplasms
Evaluation of the prognostic role of a panel of biomarkers in stage IB-IIIA non-small cell lung cancer patients.
Neoplasms
Extracts of Koelreuteria henryi Dummer induce apoptosis and autophagy by inhibiting dihydrodiol dehydrogenase, thus enhancing anticancer effects.
Neoplasms
Glutathione-related enzymes contribute to resistance of tumor cells and low toxicity in normal organs to artesunate.
Neoplasms
Hepatocyte growth factor and HER2/neu downregulate expression of apoptosis-inducing factor in non-small cell lung cancer.
Neoplasms
Inhibition of 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) activity of human lung microsomes by genistein, daidzein, coumestrol and C(18)-, C(19)- and C(21)-hydroxysteroids and ketosteroids.
Neoplasms
Temporal and spatial patterns of ovarian gene transcription following an ovulatory dose of gonadotropin in the rat.
Neoplasms
Ubiquitous induction of resistance to platinum drugs in human ovarian, cervical, germ-cell and lung carcinoma tumor cells overexpressing isoforms 1 and 2 of dihydrodiol dehydrogenase.
Neoplasms
[Gene expression profiling of human ovarian epithelial tumors by digo nucleotide microarray]
Neoplasms, Germ Cell and Embryonal
Dihydrodiol dehydrogenases regulate the generation of reactive oxygen species and the development of cisplatin resistance in human ovarian carcinoma cells.
Optic Nerve Injuries
Altered expression of 3 alpha-hydroxysteroid dehydrogenases in human glaucomatous optic nerve head astrocytes.
Ovarian Neoplasms
Overexpression of dihydrodiol dehydrogenase is associated with cisplatin-based chemotherapy resistance in ovarian cancer patients.
Pneumonia
Increased annexin A1 and A2 levels in bronchoalveolar lavage fluid are associated with resistance to respiratory disease in beef calves.
Prostatic Hyperplasia
Expression and characterization of recombinant type 2 3 alpha-hydroxysteroid dehydrogenase (HSD) from human prostate: demonstration of bifunctional 3 alpha/17 beta-HSD activity and cellular distribution.
Prostatic Hyperplasia
Function of human brain short chain L-3-hydroxyacyl coenzyme A dehydrogenase in androgen metabolism.
Prostatic Neoplasms
5alpha-androstane-3alpha,17beta-diol selectively activates the canonical PI3K/AKT pathway: a bioinformatics-based evidence for androgen-activated cytoplasmic signaling.
Prostatic Neoplasms
5alpha-androstane-3alpha,17beta-diol supports human prostate cancer cell survival and proliferation through androgen receptor-independent signaling pathways: implication of androgen-independent prostate cancer progression.
Stomach Neoplasms
Identification of genes differentially expressed between gastric cancers and normal gastric mucosa with cDNA microarrays.
Stomach Neoplasms
Overexpression of dihydrodiol dehydrogenase as a prognostic marker in resected gastric cancer patients.
Uterine Cervical Neoplasms
Infection of human papillomavirus and overexpression of dihydrodiol dehydrogenase in uterine cervical cancer.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0027
(5beta,20R)-20-hydroxypregnan-3-one
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.179
3-oxo-deoxycholic acid
R7B6R4
coenzyme: NADPH, pH 7.0, temperature not specified in the publication
0.0021
5beta-androstane-3,17-dione
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
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
0.003
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
0.004
Dehydrolithocholic acid
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.155
deoxycholic acid
R7B6R4
coenzyme: NADP+, pH 10, temperature not specified in the publication
0.0012
17beta-hydroxy-5alpha-androstan-3-one
-
cloned human liver enzyme type I
0.0192
17beta-hydroxy-5alpha-androstan-3-one
-
cloned human liver enzyme type II
0.046
3alpha-hydroxy-5alpha-androstan-17-one
-
recombinant wild type enzyme
0.038
9,10-phenanthrenequinone
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
additional information
(11S,12S)-11,12-dihydrobenzo[g]chrysene-11,12-diol
racemic benzo[g]chrysene-11,12-dihydrodiol derived from the fjord-region parent hydrocarbon benzo[g]chrysene is oxidized with a kcat/Km of 1520 min/mM, which is more than 100 times greater than that observed with benzo[a]pyrene-7,8-dihydrodiol
additional information
benzo[a]pyrene-7,8-dihydrodiol
kcat/Km of 39 min/mM
additional information
additional information
-
transient-state and steady-state kinetics
-
additional information
additional information
-
steady-state kinetics
-
additional information
additional information
-
transient single and multiple turnover kinetics, stopped flow kinetics, isotope kinetics, ligand binding analysis, kinetics with deuterium-substituted cofactor and binary complex of enzyme and cofactor, overview
-
additional information
additional information
-
stereoselectivity, kinetics
-
additional information
additional information
-
equilibrium kinetics of wild-type and mutant enzymes
-
additional information
additional information
-
cofactor kinetics of wild-type and mutant enzymes, overview
-
additional information
additional information
-
kinetics of wild-type and mutant enzymes in presence or absence of CAPS and methylamine, overview
-
additional information
additional information
-
kinetics in absence and presence of co-solvents, overview
-
additional information
additional information
-
steady-state, transient state kinetics, and kinetic isotope effects, kinetic analysis and mechanism, ordered bi-bi mechanism, detailed overview
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
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
54.5
3-oxo-deoxycholic acid
R7B6R4
coenzyme: NADPH, pH 7.0, temperature not specified in the publication
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
55.9
deoxycholic acid
R7B6R4
coenzyme: NADP+, pH 10, temperature not specified in the publication
0.00063
(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
-
cofactor NADP+, pH 7.0, 25°C, steroid oxidation, recombinant mutant W227A
0.37
(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
-
cofactor NADP+, pH 7.0, 25°C, steroid oxidation, recombinant wild-type enzyme
0.8
(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
-
cofactor NADP+, pH 7.0, 25°C, steroid oxidation, recombinant mutant R276M
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
-
cofactor NAD+, pH 7.0, 25°C, steroid oxidation, recombinant wild-type enzyme
0.037
5alpha-dihydroprogesterone
-
cofactor NADPH, pH 7.0, 25°C, steroid reduction, recombinant mutant W227A
0.3
5alpha-dihydroprogesterone
-
cofactor NADPH, pH 7.0, 25°C, steroid reduction, recombinant wild-type enzyme
0.4
5alpha-dihydroprogesterone
-
cofactor NADPH, pH 7.0, 25°C, steroid reduction, recombinant mutant R276M
0.43
5alpha-dihydroprogesterone
-
cofactor NADH, pH 7.0, 25°C, steroid reduction, recombinant wild-type enzyme
0.183
9,10-phenanthrenequinone
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.83
androsterone
-
steady-state, pH 8.0, 25°C, recombinant wild-type enzyme
0.022
Dehydrolithocholic acid
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
additional information
additional information
-
kcat in steady-state, single turnover, burst in multiple turnover, steady-state in multiple turnover
-
additional information
additional information
-
single turnover, and multiple burst and steady-state in turnover, kinetic isotope effects with 4-pro-R-[2H]-NADPH on recombinant wild-type and mutant enzymes
-
additional information
additional information
-
cofactor kinetics of wild-type and mutant enzymes, overview
-
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
581.6
12-oxo-deoxycholic acid
R7B6R4
coenzyme: NADPH, pH 7.0, temperature not specified in the publication
304.5
3-oxo-deoxycholic acid
R7B6R4
coenzyme: NADPH, pH 7.0, temperature not specified in the publication
0.015
3-oxodeoxycholic acid
R7B6R4
coenzyme: NADPH, pH 6.5, temperature not specified in the publication
0.078
isodeoxycholic acid
R7B6R4
coenzyme: NADP+, pH 9.5, temperature not specified in the publication
71.6
deoxycholic acid
R7B6R4
coenzyme: NADP+, pH 7.0, temperature not specified in the publication
360.6
deoxycholic acid
R7B6R4
coenzyme: NADP+, pH 10, temperature not specified in the publication
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
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
additional information
additional information
-
more Ki values given for different inhibitors of androsterone oxidation, 9,10-phenanthrenequinone- and 5alpha-androstane-3,17-dione reduction
-
0.00001
Cibacron blue
-
slope effect, 0.025 mM androsterone, varying NADP+ concentrations
0.0002
Cibacron blue
-
slope effect, 0.25 mM NADP+, varying androsterone concentrations
0.0005
Cibacron blue
-
intercept effect, 0.25 mM NADP+, varying androsterone concentrations
0.0029
Hexestrol
-
slope effect, 0.25 mM NADP+, varying androsterone concentrations
0.0031
Hexestrol
-
intercept effect, 0.025 mM androsterone, varying NADP+ concentrations
0.0002
indomethacin
-
competitive, for 9,10-phenanthrenequinone and 5alpha-androstane-3,17-dione reduction at pH 6.0
0.000835
indomethacin
-
competitive for androstene oxidation at pH 7.0. IC50 is 0.003 mM at H 7.0, 0.045 at pH 9.0
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0136
(2E)-3-(4-bromophenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
Homo sapiens
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
Homo sapiens
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
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
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
0.009
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
0.00031
Flufenamic acid
Homo sapiens
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.0040 mM in fluorometric assay, in vitro IC50: 0.00031 mM in fluorometric assay
0.000735
indomethacin
Rattus norvegicus
-
competitive, IC50 for reduction of 9,10-phenanthrenequinone by NADPH at pH6.0 is 0.000735 mM
0.00333
indomethacin
Rattus norvegicus
-
competitive, IC50 for oxidation of androsterone by NAD+ at pH 7.0 0.00333 mM
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
0.008 - 4
-
determined for several substrates,with best activities for 9,10-phenanthrenequinone, 4-nitrobezaldehyde and androsterone
0.07
-
recombinant AKR1C17 in cell extract, substrate 4-androsten-3alpha-ol-17-one
0.08
0.1
0.23
-
purified recombinant AKR1C17, substrate 4-androsten-3alpha-ol-17-one
1.6
additional information
additional information
-
enzyme contains conserved catalytic tetrad of Asp50, Tyr55, Lys84 and His117
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5 - 11
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
37
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
the enzyme expression is positively correlated to adiposity in woman
brenda
high expression and activity in astrocytes of glaucomatous optic nerve head
brenda
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
brenda
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
brenda
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
brenda
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
brenda
-
strong isoform AKR1C3 immunoreactivity in columnar epithelium but only weak immunoreactivity in squamous epithelium of the gastrointestinal junction
brenda
-
primary, high expression and activity in healthy hepatocytes
brenda
-
strong isoform AKR1C3 immunoreactivity in bronchial epithelium but not in bronchial glands or alveolar pneumocytes
brenda
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
brenda
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
brenda
-
6fold higher expression level in female than in male pituitary
brenda
-
lumbar, of naive, sham-operated and neuropathic rats, enzyme expression analysis and cellular distribution in neurons and glial cells, immunohistochemic analysis, overview
brenda
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
brenda
additional information
-
the urothelial epithelium lining the renal pelvis is strongly immunoreactive, but stromal cells in the underlying supporting connective tissue are negative
brenda
-
only a small number of epithelial cells are immunoreactive with both nuclear and cytoplasmic reactivity
brenda
-
no activity in the stromal cells or endothelial cells, but weak immunoreactivity in the epididymal epithelial cells
brenda
-
in renal cortex, endothelial cells of the glomeruli lack immunoreactivity for AKR1C3, but the Bowmans capsule and mesangial cells are strongly reactive, as well as larger epithelial cells of the medulla, overview
brenda
-
specific expression of AKR1C17, two enzymes are expressed more highly in renal cortex than in the medulla
brenda
in primary prostate stromal cells, co-localization with RODH like 3alpha/17beta-HSD, EC 1.1.1.239
brenda
-
epithelial cells, but not the stromal cells or endothelial cells
brenda
-
in Leydig cells, but no or poor activity in germ cells and Sertoli cells
brenda
additional information
-
tissue distribution of AKR1C3, immunohistochemic analysis, overview
brenda
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
brenda
additional information
-
the androgen-inactivating enzyme is selectively expressed in female tissue, while it is mostly absent in male tissue, tissue distribution, overview
brenda
additional information
-
indomethacin-sensitive 3alpha-hydroxysteroid dehydrogenase widely distributed in prostate, spleen, heart, testis, small intestine, stomach, lung and brain
brenda
additional information
-
low activities found in dog and rabbit liver, no significant activities are detected in extracts of beef, hog, guinea pig, mouse and human liver
brenda
additional information
-
tissue distribution of AKR1C9, immunohistochemic analysis, overview
brenda
additional information
-
indomethacin-sensitive 3alpha-hydroxysteroid dehydrogenase widely distributed in prostate, spleen, heart, testis, small intestine, stomach, lung and brain
-
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
additional information
-
tissue-dependent subcellular localization, overview
-
brenda
additional information
-
subcellular localization of isozymes, overview
-
brenda
additional information
-
tissue-dependent subcellular localization, overview
-
brenda
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
comparison of a common non-synonymous polymorphism, AKR1C3-2 in the gene encoding the enzyme 3alpha-HSD2/17beta-HSD5 and a synonymous SNP, rs248793, in SRD5A1, which encodes 5alpha-reductase: for caucasian males, carriers of the alcohol dependence-protective AK1C3-2 G-allele have higher levels of 5alpha-androstane-3alpha1beta-diol relative to the precursor 3alpha,5alpha-androsterone than C-allele homozygotes. AKR1C3-2 G-allele carriers exhibit greater increases in heart rate and stimulant and sedative effects of alcohol than C-allele homozygotes
physiological function
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
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
the enzyme 3alpha-hydroxysteroid dehydrogenase is involved in neuroactive steroid biosynthesis. Genetic variation in a region of chromosome 10 containing the genes AKR1C1, AKR1C3 and AKR1C4, which encode 3 isoforms of 3alpha-HSD, is associated with variation in subjective alcohol response. Enzyme mutant variant H5Q is associated with reduced risk of both alcohol dependence and bladder cancer, moderates the stimulant or sedative effects of alcohol
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). AK1C2_HUMAN
323
0
36735
Swiss-Prot
other Location (Reliability: 3)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
32000
-
x * 32000, about, recombinant His-tagged wild-type and mutant enzymes, SDS-PAGE
33000
34000
37000
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
monomer
tetramer
additional information
?
-
x * 32000, about, recombinant His-tagged wild-type and mutant enzymes, SDS-PAGE
dimer
-
the dimerization takes place via an interface axis. The formation of a tetramer is blocked in 3alpha-HSD/CR by the presence of a predominantly alpha-helical subdomain which is missing in all other SDRs of known structure, overview
additional information
-
domain structure, the enzyme possessses a 28 amino acids insertion into the classical Rossmann-fold motif between strand betaE and helix alphaF, preventing the formation of a four helix bundle and enables the dimerization via a P-axis interface, structure homology modelling and simulation, structure comparison, overview
additional information
-
comparison of the folding topologies found in the crystal structures of the holo-enzyme and the apo-enzyme, structural changes in solution, overview
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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
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
purified recombinant wild-type enzyme, hanging drop vapour diffusion method, 4°C, mixing of equal volumes of 14 mg/ml protein solution and mother liquor containing 0.1 M sodium citrate, pH 6.5, 0.1 M ammonium acetate, and 24-30% PEG 4000, cryoprotection of crystals in 20% ethylene glycol in mother liquor, X-ray diffraction structure determination and analysis at 1.9 A resolution, molecular replacement study
purified enzyme with NADH, hanging drop vapour diffusion method, 4°C, in presence of 1.4 M ammonium sulfate, 0.14 M NaCl, and 0.1 M Tris, pH 9.0, rod cluster crystals appear within 1 week, X-ray diffraction structure determination and analysis at 1.8 A resolution, modeling
-
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K159A
K159M
-
site-directed mutagenesis, the mutation changes the rate-limiting step to the hydride transfer, proton transfer is blocked in the mutant but can be rescued using exogenous proton acceptors, such as buffers, small primary amines, and azide, overview
S114A
-
site-directed mutagenesis, altered kinetics in comparison to the wild-type enzyme
S114A/Y155F
-
site-directed mutagenesis, altered kinetics in comparison to the wild-type enzyme
Y155F
-
site-directed mutagenesis, altered kinetics in comparison to the wild-type enzyme
Y155F/K159A
-
site-directed mutagenesis, altered kinetics in comparison to the wild-type enzyme
H5Q
a naturally occuring non-synonymous single nucleotide polymorphism (SNP), rs12529 C>G or AKR1C3-2 in exon 1 of AKR1C3
R301L
site-directed mutagenesis, the mutation greatly affects the 3alpha-hydroxysteroid dehydrogenase activity towards 5alpha-dihydrotestosterone and almost completely abolishes the 17beta-hydroxysteroid dehydrogenase activity of the enzyme
R304L
site-directed mutagenesis, the mutation greatly affects the 3alpha-hydroxysteroid dehydrogenase activity towards 5alpha-dihydrotestosterone and abolishes the 17beta-hydroxysteroid dehydrogenase activity of the enzyme
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
F129A
H117A
-
1/500th catalytic efficiency of wild type, unlikely to be the general amino acid for catalysis
L54A
N306A
Q190A
site-directed mutagenesis, decreased binding affinity to NADP(H), only binding of cofactor is affected, residue is located at the catalytic cente
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
S166A
site-directed mutagenesis, decreased binding affinity to NADP(H), only binding of cofactor is affected, residue is located at the catalytic center
T226A
T24A
W148Y
W227A
W227Y
W86Y
Y205F
-
kinetically indistinguishable from the wild type, no general amino acid for catalysis in 3alpha-hydroxysteroid dehydrogenase
Y216S
site-directed mutagenesis, decreased binding affinity to NADP(H), only binding of cofactor is affected, residue is located at the catalytic cente
Y310A
Y55F
-
inactive, unable to perform steroid oxidoreduction, strongest candidate for the general amino acid
additional information
K159A
-
site-directed mutagenesis, altered kinetics in comparison to the wild-type enzyme
K159A
-
site-directed mutagenesis, the mutation changes the rate-limiting step to the hydride transfer, proton transfer is blocked in the mutant but can be rescued using exogenous proton acceptors, such as buffers, small primary amines, and azide, 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
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
-
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
R276M
elimination of salt bridge between Arg276 and the 2'-phosphate of AMP results in 100fold decrease of the affinity to NADP(H)
R276M
-
site-directed mutagenesis, mutant does no longer form a salt-linkage to the phosphate of 2'-AMP, and does no longer bind tightly to NAD(P)H, the burst phase kinetics for the NADP+-dependent oxidation of 3alpha-diol is eliminated
R276M
-
site-directed mutagenesis, the mutant shows slightly increased preference for the reduction reaction compared to the wild-type enzyme
T226A
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme, effects of mutation on binding constants and kinetics, overview
T226A
smallest change in kcat/Km is observed when alanine is used to substitute hydrophilic residues
T24A
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme, effects of mutation on binding constants and kinetics, overview
T24A
smallest change in kcat/Km is observed when alanine is used to substitute hydrophilic residues
W148Y
-
site-directed mutagenesis, kinetically similar to wild type enzyme, no function in ligand binding
W148Y
-
can catalyse steroid oxidoreduction similar to wild type, plays no role in steroid binding or catalysis
W227A
-
site-directed mutagenesis, highly reduced activity compared to the wild-type enzyme, 23fold decreased affinity for progesterone, effects of mutation on binding constants and kinetics, overview
W227A
-
site-directed mutagenesis, highly reduced activity compared to the wild-type, very slow chemical transformation
W227Y
-
site-directed mutagenesis, important role in binding steroid hormones, but not small substrates or inhibitors, interacts with the C and/or D-rings of steroid ligand
W86Y
-
site-directed mutagenesis, important in binding steroids and non-steroidal anti-inflamatory drugs, region in which it resides is part of the substrate/inhibitor binding pocket, near the A-, and B-rings of bound steroid
Y310A
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme, effects of mutation on binding constants and kinetics, overview
additional information
-
co-immobilization of the enzyme with diaphorase of Clostridum sp. onto alkylamine glass beads through glutaraldehyde coupling for determination of bile acids, method opimization and evaluation, loss of 30% of activity after 4 months of regular use, overview
additional information
-
potential CoA binding sites spanning residues 182 to 193. N-terminal region is thought to contain the NAD(P)+ binding site, the middle and C-terminal regions the active site of the enzyme
additional information
-
potential CoA binding sites spanning residues 182 to 193. N-terminal region is thought to contain the NAD(P)+ binding site, the middle and C-terminal regions the active site of the enzyme
-
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
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45
45
-
inactivated in absence of ligand, protected only by the addition of NADP+
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-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
-
4°C, 10 mM-Tris/HCl, pH 8.0, 5 mM 2-mercaptoethanol, 0.5 mM EDTA, 20% glycerol
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
ammonium sulfate precipitation, Ca2(PO4)2 gel extraction, ethanol precipitation
-
ammonium sulfate precipitation, Q-Sepharose, Red A, HA-Ultrogel, Sephadex G-100, copurification with NAD+ dependent enzyme
-
anion exchange and Blue Sepharose column
CaCl2 and ammonium sulfate fractionation, DEAE-cellulose- and hydroxyapatite chromatography, chromatofocusing, Sephadex G-100
-
N167A chromatofocusing and gel filtration introduced between the to others chromatography steps
native enzyme 73.3fold from liver by ammonium sulfate, anion-exchange chromatography, gel filtration, and affinity chromatography
-
recombinant enzyme from Escherichia coli strain C41(DE3) in a successive chromatographic procedure, to homogeneity
-
recombinant GST-fusion wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by glutathione affinity and anion exchange chromatography, and gel filtration to homogeneity
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli by nickel affinity chromatography
-
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain Bl21(DE3) by nickel affinity chromatography, to homogeneity
-
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
-
recombinant wild-type and mutant enzymes ifrom Escherichia coli strain BL21(DE3)
-
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
AKR1C3 PCR fragment cloned into pCR2.1-TOPO and then into vector pET15b and overexpressed in Escherichia coli strain BL21(DE3)
-
expression and promoter activity analysis, genetic enzyme regulation, overview
expression of His-tagged wild-type and mutant enzymes in Escherichia coli
-
expression of wild-type and mutant AKR1C17s in Escherichia coli strain BL21(DE3)
-
expression of wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
-
genetic variation in a region of chromosome 10 containing the genes AKR1C1, AKR1C3 and AKR1C4, which encode 3 isoforms of 3alpha-HSD
overexpression of GST-fusion wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
overexpression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
-
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
-
transient functional expression in PC3 and COS-1 cells, trans-activation of the enzyme using a CAT reporter gene assay, overview
wild-type enzyme and mutants are overexpressed in Escherichia coli DH5alpha
-
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
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 expression of isoform AKR1C3 is reduced in both hyperplastic and carcinomatous endometrial epithelium
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
-
co-immobilization of the enzyme with diaphorase of Clostridum sp. onto alkylamine glass beads through glutaraldehyde coupling for determination of bile acids in serum and bile in a cost-effective colorimetric assay
drug development
medicine
synthesis
-
the enzyme is useful in reductive production of steroids. In a coupled-enzyme system comprising HSDH and formate dehydrogenase, a twofold increase in production rate of androsterone is obtained when utilizing 1-butyl-3-methylimidazolium L-lactate with NADH regeneration
drug development
-
the enzyme is a target for treatment of chronic pain in neuropathic diseases, overview
drug development
-
2'-hydroxyflavanone may be useful for clinical therapy of malignancies where AKR1C3 is overexpressed like in prostate and breast cancer
medicine
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
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
-
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
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ohmura, M.; Hara, A.; Nakagawa, M.; Sawada, H.
Demonstration of 3alpha(17beta)-hydroxysteroid dehydrogenase distinct from 3alpha-hydroxysteroid dehydrogenase in hamster liver
Biochem. J.
266
583-589
1990
Mesocricetus auratus
brenda
Sawada, H.; Hara, A.; Ohmura, M.; Nakayama, T.; Deyashi, Y.
Kinetic and stereochemical characterization of hamster liver 3alpha-hydroxysteroid dehydrogenase and 3alpha(17beta)-hydroxysteroid dehydrogenase
J. Biochem.
109
770-775
1991
Mesocricetus auratus
brenda
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
brenda
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
brenda
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
brenda
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
brenda
Tomkins, G.M.
A mammalian 3alpha-hydroxysteroid dehydrogenase
J. Biol. Chem.
218
437-447
1956
Rattus norvegicus
brenda
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
brenda
Mallonee, D.H.; Lijewski, M.A.; Hylemon, P.B.
Expression in Escherichia coli and characterization of a bile acid-inducible 3alpha-hydroxysteroid dehydrogenase from Eubacterium sp. strain VPI 12708
Curr. Microbiol.
30
259-263
1995
Eubacterium sp., Eubacterium sp. VPI 12708
brenda
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
brenda
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
brenda
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
brenda
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)
brenda
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
brenda
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
brenda
Matsunaga, T.; Shintani, S.; Hara, A.
Multiplicity of mammalian reductases for xenobiotic carbonyl compounds
Drug Metab. Pharmacokinet.
21
1-18
2006
Homo sapiens (P52895), Homo sapiens
brenda
Hwang, C.; Chang, Y.; Hsu, C.; Hsu, H.; Li, C.; Pon, H.
Mechanistic roles of Ser-114, Tyr-155, and Lys-159 in 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase from Comamonas testosteroni
J. Biol. Chem.
280
3522-3528
2005
Comamonas testosteroni
brenda
Jin, Y.; Penning, T.M.
Multiple steps determine the overall rate of the reduction of 5alpha-dihydrotestosterone catalyzed by human type 3 3alpha-hydroxysteroid dehydrogenase: implications for the elimination of androgens
Biochemistry
45
13054-13063
2006
Homo sapiens
brenda
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
brenda
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
brenda
Rani, K.; Garg, P.; Pundir, C.S.
Discrete analysis of bile acid in serum and bile with 3alpha-hydroxysteroid dehydrogenase and diaphorase immobilized onto alkylamine glass beads
Indian J. Biochem. Biophys.
43
98-104
2006
Comamonas testosteroni
brenda
Nakamura, S.; Oda, M.; Kataoka, S.; Ueda, S.; Uchiyama, S.; Yoshida, T.; Kobayashi, Y.; Ohkubo, T.
Apo- and holo-structures of 3alpha-hydroxysteroid dehydrogenase from Pseudomonas sp. B-0831. Loop-helix transition induced by coenzyme binding
J. Biol. Chem.
281
31876-31884
2006
Pseudomonas sp.
brenda
Okochi, M.; Nakagawa, I.; Kobayashi, T.; Hayashi, S.; Furusaki, S.; Honda, H.
Enhanced activity of 3alpha-hydroxysteroid dehydrogenase by addition of the co-solvent 1-butyl-3-methylimidazolium (l)-lactate in aqueous phase of biphasic systems for reductive production of steroids
J. Biotechnol.
128
376-382
2006
Comamonas testosteroni
brenda
Steckelbroeck, S.; Oyesanmi, B.; Jin, Y.; Lee, S.H.; Kloosterboer, H.J.; Penning, T.M.
Tibolone metabolism in human liver is catalyzed by 3alpha/3beta-hydroxysteroid dehydrogenase activities of the four isoforms of the aldo-keto reductase (AKR)1C subfamily
J. Pharmacol. Exp. Ther.
316
1300-1309
2006
Homo sapiens
brenda
Wiebe, J.P.; Souter, L.; Zhang, G.
Dutasteride affects progesterone metabolizing enzyme activity/expression in human breast cell lines resulting in suppression of cell proliferation and detachment
J. Steroid Biochem. Mol. Biol.
100
129-140
2006
Homo sapiens
brenda
Bellemare, V.; Labrie, F.; Luu-The, V.
Isolation and characterization of a cDNA encoding mouse 3alpha-hydroxysteroid dehydrogenase: an androgen-inactivating enzyme selectively expressed in female tissues
J. Steroid Biochem. Mol. Biol.
98
18-24
2006
Mus musculus
brenda
Bauman, D.R.; Steckelbroeck, S.; Williams, M.V.; Peehl, D.M.; Penning, T.M.
Identification of the major oxidative 3alpha-hydroxysteroid dehydrogenase in human prostate that converts 5alpha-androstane-3alpha,17beta-diol to 5alpha-dihydrotestosterone: a potential therapeutic target for androgen-dependent disease
Mol. Endocrinol.
20
444-458
2006
Homo sapiens (P52895), Homo sapiens
brenda
Yee, D.J.; Balsanek, V.; Bauman, D.R.; Penning, T.M.; Sames, D.
Fluorogenic metabolic probes for direct activity readout of redox enzymes: Selective measurement of human AKR1C2 in living cells
Proc. Natl. Acad. Sci. USA
103
13304-13309
2006
Homo sapiens
brenda
Couture, J.F.; de Jesus-Tran, K.P.; Roy, A.M.; Cantin, L.; Cote, P.L.; Legrand, P.; Luu-The, V.; Labrie, F.; Breton, R.
Comparison of crystal structures of human type 3 3alpha-hydroxysteroid dehydrogenase reveals an 'induced-fit' mechanism and a conserved basic motif involved in the binding of androgen
Protein Sci.
14
1485-1497
2005
Homo sapiens (P52895), Homo sapiens
brenda
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
brenda
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
brenda
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
brenda
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)
brenda
Chang, Y.H.; Chuang, L.Y.; Hwang, C.C.
Mechanism of proton transfer in the 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase from Comamonas testosteroni
J. Biol. Chem.
282
34306-34314
2007
Comamonas testosteroni
brenda
Hoffmann, F.; Sotriffer, C.; Evers, A.; Xiong, G.; Maser, E.
Understanding oligomerization in 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase from Comamonas testosteroni: an in silico approach and evidence for an active protein
J. Biotechnol.
129
131-139
2007
Comamonas testosteroni
brenda
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
brenda
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
brenda
Skarydova, L.; Zivna, L.; Xiong, G.; Maser, E.; Wsol, V.
AKR1C3 as a potential target for the inhibitory effect of dietary flavonoids
Chem. Biol. Interact.
178
138-144
2009
Homo sapiens
brenda
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)
brenda
Bjrkhem, 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
brenda
Jackson, V.J.; Yosaatmadja, Y.; Flanagan, J.U.; Squire, C.J.
Structure of AKR1C3 with 3-phenoxybenzoic acid bound
Acta Crystallogr. Sect. F
68
409-413
2012
Homo sapiens (P42330)
brenda
Adeniji, A.O.; Twenter, B.M.; Byrns, M.C.; Jin, Y.; Winkler, J.D.; Penning, T.M.
Discovery of substituted 3-(phenylamino)benzoic acids as potent and selective inhibitors of type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3)
Bioorg. Med. Chem. Lett.
21
1464-1468
2011
Homo sapiens (P42330)
brenda
Chen, M.; Adeniji, A.O.; Twenter, B.M.; Winkler, J.D.; Christianson, D.W.; Penning, T.M.
Crystal structures of AKR1C3 containing an N-(aryl)amino-benzoate inhibitor and a bifunctional AKR1C3 inhibitor and androgen receptor antagonist. Therapeutic leads for castrate resistant prostate cancer
Bioorg. Med. Chem. Lett.
22
3492-3497
2012
Homo sapiens (P42330)
brenda
Sinreih, M.; Sosic, I.; Beranic, N.; Turk, S.; Adeniji, A.O.; Penning, T.M.; Rizner, T.L.; Gobec, S.
N-Benzoyl anthranilic acid derivatives as selective inhibitors of aldo-keto reductase AKR1C3
Bioorg. Med. Chem. Lett.
22
5948-5951
2012
Homo sapiens (P42330)
brenda
Matsunaga, T.; Hojo, A.; Yamane, Y.; Endo, S.; El-Kabbani, O.; Hara, A.
Pathophysiological roles of aldo-keto reductases (AKR1C1 and AKR1C3) in development of cisplatin resistance in human colon cancers
Chem. Biol. Interact.
202
234-242
2013
Homo sapiens (P42330)
brenda
Heinrich, D.M.; Flanagan, J.U.; Jamieson, S.M.; Silva, S.; Rigoreau, L.J.; Trivier, E.; Raynham, T.; Turnbull, A.P.; Denny, W.A.
Synthesis and structure-activity relationships for 1-(4-(piperidin-1-ylsulfonyl)phenyl)pyrrolidin-2-ones as novel non-carboxylate inhibitors of the aldo-keto reductase enzyme AKR1C3
Eur. J. Med. Chem.
62
738-744
2013
Homo sapiens (P42330)
brenda
Gazvoda, M.; Beranic, N.; Turk, S.; Burja, B.; Kocevar, M.; Rizner, T.L.; Gobec, S.; Polanc, S.
2,3-diarylpropenoic acids as selective non-steroidal inhibitors of type-5 17?-hydroxysteroid dehydrogenase (AKR1C3)
Eur. J. Med. Chem.
62
89-97
2013
Homo sapiens (P42330)
brenda
Zakharov, V.; Lin, H.K.; Azzarello, J.; McMeekin, S.; Moore, K.N.; Penning, T.M.; Fung, K.M.
Suppressed expression of type 2 3alpha/type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3) in endometrial hyperplasia and carcinoma
Int. J. Clin. Exp. Pathol.
3
608-617
2010
Homo sapiens (P42330)
brenda
Miller, V.L.; Lin, H.K.; Murugan, P.; Fan, M.; Penning, T.M.; Brame, L.S.; Yang, Q.; Fung, K.M.
Aldo-keto reductase family 1 member C3 (AKR1C3) is expressed in adenocarcinoma and squamous cell carcinoma but not small cell carcinoma
Int. J. Clin. Exp. Pathol.
5
278-289
2012
Homo sapiens
brenda
Brozic, P.; Turk, S.; Adeniji, A.O.; Konc, J.; Janezic, D.; Penning, T.M.; Lanisnik Rizner, T.; Gobec, S.
Selective inhibitors of aldo-keto reductases AKR1C1 and AKR1C3 discovered by virtual screening of a fragment library
J. Med. Chem.
55
7417-7424
2012
Homo sapiens (P42330)
brenda
Byrns, M.C.; Mindnich, R.; Duan, L.; Penning, T.M.
Overexpression of aldo-keto reductase 1C3 (AKR1C3) in LNCaP cells diverts androgen metabolism towards testosterone resulting in resistance to the 5alpha-reductase inhibitor finasteride
J. Steroid Biochem. Mol. Biol.
130
7-15
2012
Homo sapiens (P42330)
brenda
Milivojevic, V.; Feinn, R.; Kranzler, H.R.; Covault, J.
Variation in AKR1C3, which encodes the neuroactive steroid synthetic enzyme 3alpha-HSD type 2 (17beta-HSD type 5), moderates the subjective effects of alcohol
Psychopharmacology
231
3597-3608
2014
Homo sapiens (P42330)
brenda
Mythen, S.; Devendran, S.; Mndez-Garca, C.; Cann, I.; Ridlon, J.
Targeted synthesis and characterization of a gene cluster encoding NAD(P)H-dependent 3alpha-, 3beta-, and 12alpha-hydroxysteroid dehydrogenases from Eggerthella CAG 298, a gut metagenomic sequence
Appl. Environ. Microbiol.
84
e02475-17
2018
Eggerthella sp. CAG:298 (R7B6R4)
brenda
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