Information on EC 1.1.1.213 - 3alpha-hydroxysteroid 3-dehydrogenase (Re-specific)

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

EC NUMBER
COMMENTARY hide
1.1.1.213
-
RECOMMENDED NAME
GeneOntology No.
3alpha-hydroxysteroid 3-dehydrogenase (Re-specific)
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
allopregnanolone biosynthesis
-
-
bile acid biosynthesis, neutral pathway
Steroid hormone biosynthesis
-
-
testosterone and androsterone degradation to androstendione
-
-
SYSTEMATIC NAME
IUBMB Comments
3alpha-hydroxysteroid:NAD(P)+ 3-oxidoreductase (Re-specific)
The enzyme acts on multiple 3alpha-hydroxysteroids. Re-specific with respect to NAD+ or NADP+ [cf. EC 1.1.1.50, 3alpha-hydroxysteroid 3-dehydrogenase (Si-specific)]. Enzymes whose stereo-specificity with respect to NAD+ or NADP+ is not known are described by EC 1.1.1.357, 3alpha-hydroxysteroid 3-dehydrogenase.
CAS REGISTRY NUMBER
COMMENTARY hide
9028-56-2
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strain VPI 12708
-
-
Manually annotated by BRENDA team
Eubacterium sp. VPI 12708
strain VPI 12708
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
strain B-0831
-
-
Manually annotated by BRENDA team
strain B-0831
-
-
Manually annotated by BRENDA team
Rattus norvegicus Sprangue-Dawley
Sprangue-Dawley
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(11S,12S)-11,12-dihydrobenzo[g]chrysene-11,12-diol + NADP+
? + NADPH + H+
show the reaction diagram
-
enzyme is stereoselective for benzo[g]chrysene-11S,12S-dihydrodiol
-
-
?
(S)-alpha-tetralol + NADP+
alpha-tetralone + NADPH + H+ [View the structure]
show the reaction diagram
-
-
-
-
?
(S)-tetralol + NADP+
? + NADPH
show the reaction diagram
-
-
-
-
?
1-(4'nitrophenyl)prop-2-en-1-ol + NAD+
1-(4'nitrophenyl)prop-2-en-1-one + NADH
show the reaction diagram
1-(4'nitrophenyl)prop-2-yn-1-ol + NAD+
1-(4'nitrophenyl)prop-2-yn-1-one + NADH
show the reaction diagram
1-acenaphthenol + NAD(P)+
1-acenaphthenone + NAD(P)+
show the reaction diagram
1-acenaphthenol + NADPH
?
show the reaction diagram
-
-
-
-
?
1-acetophenone + NADPH
1-phenylethanol + NADP+
show the reaction diagram
-
-
-
-
?
1-indanone + NADPH
?
show the reaction diagram
-
-
-
-
?
10-oxonortriptyline + NADPH
?
show the reaction diagram
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
show the reaction diagram
-
the rate of dihydrotestosterone reduction over back-conversion is 2.4 and 5.9 for prostate and epididymis, respectively
-
r
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
show the reaction diagram
17beta-hydroxy-5alpha-androstan-3-one + NADPH
3alpha,17beta-dihydroxy-5alpha-androstan + NADP+
show the reaction diagram
-
-
-
r
2 tibolone + 2 NADPH + 2 H+
3alpha-hydroxytibolone + 3beta-hydroxytibolone + 2 NADP+
show the reaction diagram
2-acetylpyridine + NADPH
1-(2-pyridyl)ethanol + NADP+
show the reaction diagram
-
stereoselective catalysis producing mainly the (S)-alcohols
-
-
?
2-decalone + NADH
? + NAD+
show the reaction diagram
-
pH 6.0
-
?
3-acetylpyridine + NADPH
1-(3-pyridyl)ethanol + NADP+
show the reaction diagram
-
low activity, stereoselective catalysis producing mainly the (S)-alcohols
-
-
?
3-ketosteroids + NADPH
3-hydroxysteroids + NADP+
show the reaction diagram
-
-
-
?
3alpha,5alpha-allopregnenolone + NAD(P)+
5alpha-dihydroprogesterone + NAD(P)H
show the reaction diagram
3alpha-androstanediol + NAD+
5alpha-dihydrotestosterone + NADH + H+
show the reaction diagram
-
steroid reduction direction is preferred
-
-
r
3alpha-hydroxy-5alpha-androstan-17-one + NAD+
5alpha-androstan-3,17-dione + NADH
show the reaction diagram
3alpha-hydroxy-5alpha-androstan-17-one + NADP+
5alpha-androstan-3,17-dione + NADPH
show the reaction diagram
4'-methoxyacetophenone + NADPH + H+
1-(4-methoxyphenyl)ethanol + NADP+
show the reaction diagram
-
-
R,S-enantiomeric product
-
?
4-acetylpyridine + NADPH
(S)-1-(4-pyridyl)ethanol + NADP+
show the reaction diagram
-
-
-
-
?
4-acetylpyridine + NADPH
1-(4-pyridyl)ethanol + NADP+
show the reaction diagram
-
stereoselective catalysis producing mainly the (S)-alcohols
-
-
?
4-androsten-3alpha-ol-17-one + NADH + H+
4-androsten-3alpha,17beta-diol + NAD+
show the reaction diagram
-
AKR1C17
-
-
r
4-androstene-3,17-dione + NADH + H+
4-androsten-3alpha-ol-17-one + NAD+
show the reaction diagram
-
low activity
-
-
r
4-bromoacetophenone + NADPH + H+
1-(4-bromophenyl)ethanol + NADP+
show the reaction diagram
-
-
-
-
?
4-cyanoacetophenone + NADPH + H+
1-(4-cyanophenyl)ethanol + NADP+
show the reaction diagram
-
-
-
-
?
4-hydroxynonenal + NADPH
?
show the reaction diagram
-
-
-
-
?
4-methylacetophenone + NADPH + H+
1-(4-methylphenyl)ethanol + NADP+
show the reaction diagram
-
-
R,S-enantiomeric product
-
?
4-nitroacetophenone + NAD(P)H
1-(4-nitrophenyl)ethanol + NAD(P)+
show the reaction diagram
-
pH 6.0
-
?
4-nitroacetophenone + NADPH + H+
1-(4-nitrophenyl)ethanol + NADP+
show the reaction diagram
-
-
-
-
?
4-nitrobenzaldehyde + NAD(P)H
(4-nitrophenyl)methanol + NAD(P)+
show the reaction diagram
4-oxo-2-nonenal + NADPH + H+
4-hydroxynonenal + NADP+
show the reaction diagram
-
-
-
-
?
5alpha-androstan-17beta-ol-3-one + NADPH + H+
5alpha-androstan-3alpha,17beta-diol + NADP+
show the reaction diagram
-
-
-
?
5alpha-androstan-3,17-dione + NAD(P)H
3alpha-hydroxy-5alpha-androstan-17-one + NAD(P)+
show the reaction diagram
5alpha-androstan-3alpha-ol-17-one + NADH + H+
5beta-androstan-3alpha,17beta-diol + NAD+
show the reaction diagram
5alpha-androstane-3,17-dione + NADH
5alpha-androstan-3alpha-ol-17-one + NAD+
show the reaction diagram
-
low activity
AKR1C9
-
r
5alpha-androstane-3alpha,17beta-diol + NADP+
5alpha-androstane-17beta-ol-3-one + NADPH
show the reaction diagram
-
-
-
r
5alpha-androstanedione + NADPH
5alpha-pregnan-3alpha-ol-20-one + NADP+
show the reaction diagram
-
-
i.e. allopregnanolone
-
?
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
show the reaction diagram
5alpha-dihydrotestosterone + NADH
?
show the reaction diagram
-
low activity
-
-
?
5alpha-dihydrotestosterone + NADPH
3alpha-androstanediol + NADP+
show the reaction diagram
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
show the reaction diagram
5alpha-dihydrotestosterone + NADPH + H+
3alpha-androstanediol + NADP+
show the reaction diagram
5alpha-pregnan-3,20-dione + NAD(P)H + H+
5alpha-pregnan-3alpha-ol-20-one + NAD(P)+
show the reaction diagram
-
regulation of the amount of allosteric agonists that can bind to the GABA receptor in brain
-
r
5alpha-pregnan-3alpha,21-diol-20-one + NADP+
5alpha-pregnan-21-ol-3,20-dione + NADPH
show the reaction diagram
-
-
-
r
5alpha-pregnane-20alpha-ol-3-one + NADH
5alpha-pregnane-3,20alpha-diol + NAD+
show the reaction diagram
-
-
-
-
?
5alpha-pregnane-3,20-dione + NADH
5alpha-pregnan-3alpha-ol-20-one + NAD+
show the reaction diagram
-
low activity
-
-
r
5beta-androstan-3alpha-ol-17-one + NAD(P)+
5beta-androstane-3,17-dione + NAD(P)H
show the reaction diagram
-
-
-
-
r
5beta-androstan-3alpha-ol-17-one + NADH
5beta-androstane-3alpha,17beta-diol + NAD+
show the reaction diagram
-
-
-
-
r
5beta-androstan-3alpha-ol-17-one + NADP+
5beta-androstan-3,17-dione + NADPH
show the reaction diagram
-
-
-
?
5beta-androstane-3,17-dione + NADH
5beta-androstan-3alpha-ol-17-one + NAD+
show the reaction diagram
-
-
-
-
r
5beta-androstane-3alpha,17beta-diol + NADP+
5beta-androstane-17beta-ol-3-one + NADPH
show the reaction diagram
-
-
-
r
5beta-cholestane-3alpha,7alpha,12alpha-triol + NADP+
7alpha,12alpha-dihydroxy-5beta-cholestan-3-one + NADPH + H+
show the reaction diagram
-
-
-
-
?
5beta-cholestane-3alpha,7alpha-diol + NADP+
7alpha-hydroxy-5beta-cholestan-3-one + NADPH + H+
show the reaction diagram
-
-
-
-
?
5beta-dihydrocortisone + NADPH
3alpha,17alpha,21-trihydroxy-5beta-pregnan-11,20-dione + NADP+
show the reaction diagram
-
-
-
?
5beta-pregnan-3alpha-ol-20-one + NAD(P)+
5beta-pregnane-3,20-dione + NAD(P)H
show the reaction diagram
-
-
-
-
r
5beta-pregnan-3alpha-ol-20-one + NADP+
5beta-pregnane-3,20-dione + NADPH
show the reaction diagram
-
-
-
r
5beta-pregnane-17alpha,20beta,21-triol-3,11-dione + NAD(P)H
5beta-pregnane-3alpha,17alpha,20beta,21-tetraal-11-one + NAD(P)+
show the reaction diagram
5beta-pregnane-20alpha-ol-3-one + NADH + H+
5beta-pregnane-3,20alpha-diol + NAD+
show the reaction diagram
-
-
-
-
?
5beta-pregnane-3,20-dione + NADH + H+
5beta-pregnan-3alpha-ol-20-one + NAD+
show the reaction diagram
-
-
-
-
r
6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one + NADH
?
show the reaction diagram
-
the enzyme produces both R- and S-form products in a ratio of 2.3 : 1
-
-
?
9,10-phenanthrenequinone + NAD(P)H
? + NAD(P)+
show the reaction diagram
9,10-phenanthrenequinone + NADH
?
show the reaction diagram
-
-
-
-
?
9-(phenylcarbonyl)-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one + NADPH
9-[hydroxy(phenyl)methyl]-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one + NADP+
show the reaction diagram
acetohexamide + NADPH
?
show the reaction diagram
acetophenone + NADPH
1-phenylethanol + NADP+
show the reaction diagram
-
-
-
-
?
androstan-17beta-ol-3-one + NADH
androstan-3alpha,17beta-diol + NAD+
show the reaction diagram
-
-
-
?
androstan-3,17-dione + NADH
androstan-3alpha-ol-17-one + NAD+
show the reaction diagram
-
-
-
?
androsterone + NAD(P)+
5alpha-androstane-3,17-dione + NAD(P)H
show the reaction diagram
-
-
-
-
r
androsterone + NAD+
5alpha-androstane-3,17-dione + NADH
show the reaction diagram
-
-
-
-
r
androsterone + NAD+
androstanedione + NADH
show the reaction diagram
androsterone + NADP+
5alpha-androstane-3,17-dione + NADPH
show the reaction diagram
-
-
-
-
r
befunolol + NADPH
?
show the reaction diagram
benzenedihydrodiol + NAD(P)+
? + NAD(P)+
show the reaction diagram
benzo[c]phenanthrene-3,4-dihydrodiol + NADP+
? + NADPH + H+
show the reaction diagram
-
enzyme metabolizes both stereoisomers of benzo[c]phenanthrene-3,4-dihydrodiol
-
-
?
beta-muricholic acid + NADH
?
show the reaction diagram
-
low activity
-
-
?
chenodeoxycholic acid + NADH
?
show the reaction diagram
-
-
-
-
?
cholic acid + NAD(P)+
3-oxocholate + NAD(P)H
show the reaction diagram
cholic acid + NADH
?
show the reaction diagram
-
low activity
-
-
?
choloyl-CoA + NAD(P)+
3-oxocholoyl-CoA + NAD(P)H + H+
show the reaction diagram
daunorubicin + NADPH
?
show the reaction diagram
dehydrolithocholic acid + NADH + H+
?
show the reaction diagram
-
-
-
-
?
deoxycholic acid + NADH
?
show the reaction diagram
-
low activity
-
-
?
deoxycholoyl-CoA + NAD(P)+
3-oxodeoxycholoyl-CoA + NAD(P)H + H+
show the reaction diagram
diacetyl + NADH
?
show the reaction diagram
-
-
-
-
?
dihydroprogesterone + NADPH
androsterone + NADP+
show the reaction diagram
-
-
-
-
?
dolasetron + NADPH
?
show the reaction diagram
etiocholane-3,17-dione + NADH
etiocholan-3alpha-ol-17-one + NAD+
show the reaction diagram
-
-
-
?
glycochenodeoxycholic acid + NADH
?
show the reaction diagram
-
-
-
-
?
glycochenodeoxycholic acid + NADP+
7alpha-hydroxy-3-oxo-5beta-cholanoyl glycine + NADPH
show the reaction diagram
-
-
-
?
glycolithocholic acid + NADH
?
show the reaction diagram
-
-
-
-
?
glycolithocholic acid + NADP+
3-oxo-5beta-cholanoyl glycine + NADPH
show the reaction diagram
-
-
-
?
glycoursodeoxycholic acid + NADH
?
show the reaction diagram
-
-
-
-
?
haloperidol + NADPH
?
show the reaction diagram
hyodeoxycholic acid + NADH
?
show the reaction diagram
-
low activity
-
-
?
isatin + NADH
?
show the reaction diagram
-
-
-
-
?
ketoprofen + NADPH
?
show the reaction diagram
ketotifen + NADPH
?
show the reaction diagram
lithocholic acid + NADH
?
show the reaction diagram
-
-
-
-
?
lithocholic acid + NADP+
dehydrolithocholic acid + NADPH
show the reaction diagram
-
-
-
r
loxoprofen + NADPH
?
show the reaction diagram
murocholic acid + NADH
?
show the reaction diagram
-
low activity
-
-
?
Naloxone + NADPH
?
show the reaction diagram
Naltrexone + NADPH
?
show the reaction diagram
oracin + NADPH
?
show the reaction diagram
oracin + NADPH
? + NADP+
show the reaction diagram
-
-
-
-
?
oxycodone + NADPH
?
show the reaction diagram
pregnane-11beta,17alpha,21-triol-3,20-dione + NADH
pregnane-3alpha,11beta,17alpha,21-tetrol-20-one + NAD+
show the reaction diagram
-
-
-
?
progesterone + NAD(P)H
3alpha-hydroxy-pregn-4-ene-20-one + NAD(P)+
show the reaction diagram
-
-
-
-
r
prostaglandin + NADP+
? + NADPH
show the reaction diagram
-
types A1, A2, B1, B2, D2, E1, E2, F1, F2alpha and 15-keto-prostaglandinE2 and F2alpha
-
-
prostaglandin-F2alpha + NADP+
prostaglandin F2 + prostaglandin B2 + NADPH
show the reaction diagram
-
-
-
?
taurolithocholic acid + NADH
?
show the reaction diagram
-
-
-
-
?
tauroursodeoxycholic acid + NADH
?
show the reaction diagram
-
-
-
-
?
testosterone + NAD(P)H + H+
4-androsten-3alpha,17beta-diol + NAD(P)+
show the reaction diagram
-
-
-
-
r
testosterone + NADH
?
show the reaction diagram
-
low activity
-
-
?
tibolone + NADPH
3-hydroxytibolone + NADP+
show the reaction diagram
ursodeoxycholic acid + NADH
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
10-oxonortriptyline + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
show the reaction diagram
2 tibolone + 2 NADPH + 2 H+
3alpha-hydroxytibolone + 3beta-hydroxytibolone + 2 NADP+
show the reaction diagram
-
i.e. tibolone, a 3-ketosteroid androgen receptor, conversion to potent estrogen receptor alpha agonists, tibolone induces estrogen receptor alpha-dependent gene promoter activity through cis-acting estrogen response elements, increases the stimulatory effect of TGF-beta on Smad-dependent gene promoter activity, and enhances prostaglandin E2-induced activity of transcription factor Runx2, overview
3alpha-hydroxytibolone is the primary metabolite
-
r
3-ketosteroids + NADPH
3-hydroxysteroids + NADP+
show the reaction diagram
P52895
-
-
-
?
3alpha,5alpha-allopregnenolone + NAD(P)+
5alpha-dihydroprogesterone + NAD(P)H
show the reaction diagram
-
i.e. 3alpha,5alpha-tetrahydroprogesterone or 3alpha,5alpha-THP, the enzyme catalyzes the biosynthesis and oxidation of 3alpha,5alpha-reduced neurosteroids as allopregnanolone, which stimulates GABAA receptors, sciatic nerves-induced analgesia results in increased enzyme levels in neuropathic rats, overview
-
-
r
3alpha-androstanediol + NAD+
5alpha-dihydrotestosterone + NADH + H+
show the reaction diagram
-
steroid reduction direction is preferred
-
-
r
4-acetylpyridine + NADPH
(S)-1-(4-pyridyl)ethanol + NADP+
show the reaction diagram
-
-
-
-
?
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
show the reaction diagram
5alpha-dihydrotestosterone + NADPH
3alpha-androstanediol + NADP+
show the reaction diagram
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
show the reaction diagram
5alpha-dihydrotestosterone + NADPH + H+
3alpha-androstanediol + NADP+
show the reaction diagram
-
steroid reduction direction is preferred
-
-
r
5alpha-pregnan-3,20-dione + NAD(P)H + H+
5alpha-pregnan-3alpha-ol-20-one + NAD(P)+
show the reaction diagram
-
regulation of the amount of allosteric agonists that can bind to the GABA receptor in brain
-
r
5beta-pregnane-17alpha,20beta,21-triol-3,11-dione + NAD(P)H
5beta-pregnane-3alpha,17alpha,20beta,21-tetraal-11-one + NAD(P)+
show the reaction diagram
-
hepatic reduction in animal tissues
-
?
9-(phenylcarbonyl)-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one + NADPH
9-[hydroxy(phenyl)methyl]-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one + NADP+
show the reaction diagram
-
competitive substrate, fluorometric activity measurement in intact cells, overview
-
-
?
acetohexamide + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
acetophenone + NADPH
1-phenylethanol + NADP+
show the reaction diagram
-
-
-
-
?
androsterone + NAD+
5alpha-androstane-3,17-dione + NADH
show the reaction diagram
-
-
-
-
r
androsterone + NAD+
androstanedione + NADH
show the reaction diagram
-
-
-
-
r
androsterone + NADP+
5alpha-androstane-3,17-dione + NADPH
show the reaction diagram
-
-
-
-
r
befunolol + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
daunorubicin + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
dolasetron + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
haloperidol + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
ketoprofen + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
ketotifen + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
loxoprofen + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
Naloxone + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
Naltrexone + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
oracin + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
oxycodone + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
tibolone + NADPH
3-hydroxytibolone + NADP+
show the reaction diagram
-
tibolone is used to treat climacteric symptoms and prevent osteoporosis, it exerts tissue-selective effects via site-specific metabolism into 3alpha- and 3beta-hydroxymetabolites and a DELTA4-isomer
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NAD(P)+
NAD(P)H
additional information
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
citrate
-
bound to the steroid-binding cavity via Tyr55 and His117, involved in the induced fit mechanism
additional information
-
non-metallo enzyme
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2E)-3-(4-bromophenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
-
93.3% inhibition at 0.1 mM
(2E)-3-(4-ethylphenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
-
89.1% inhibition at 0.1 mM
(2E)-3-(4-methylphenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
-
92.7% inhibition at 0.1 mM
(2E)-3-[4-(methylsulfanyl)phenyl]-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
-
93.5% inhibition at 0.1 mM
(E/Z)-sulfindac
-
wild-type, W86Y and W227Y
1,10-phenanthroline
-
wild-type, W86Y and W227Y
1,7-phenanthroline
-
wild-type, W86Y and W227Y
1-(4'nitrophenyl)prop-2-en-1-ol
-
inactivation dependent on NAD+ concentration, optimal at 0.5-1.0 mM NAD+, 2-mercaptoethanol prvides a concentration-dependent protection
1-(4'nitrophenyl)prop-2-en-1-one
-
inactivation can be retarded markedly in a concentration-dependent manner by both NADH and NADPH. Competitive inhibitor of NAD+ binding, measured for androsterone oxidation
1-(4'nitrophenyl)prop-2-yn-1-one
-
competitive inhibitor of NAD+ binding, measured for androsterone oxidation
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
2-[[(3-hydroxyphenyl)carbonyl]amino]-4,5-dimethoxybenzoic acid
-
-
2-[[(3-hydroxyphenyl)carbonyl]amino]-5-nitrobenzoic acid
-
-
21-hydroxypregn-4-ene-3,20-dione
-
-
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-hydroxyflavone
-
-
3-phenoxybenzoic acid
-
inhibitor carboxylic acid binds to the oxyanion site, in which the carboxylate group very closely overlays the acetate molecule found in other AKR1C3 structures and forms hydrogen bonds to the enzyme catalytic residues His117 and Tyr55, as well as to a conserved water network located in and near the SP3 subpocket. The 3-phenoxy ring extends into the SP1 subpocket and makes van der Waals contacts with the aromatic residues Phe306, Phe311 and Tyr319 that line the pocket
3-[(4-nitrophenyl)amino]benzoic acid
-
94fold selectivity for the inhibition of isoform AKR1C3 over AKR1C2
3-[[4-(methoxymethyl)phenyl]amino]benzoic acid
-
360fold selectivity for the inhibition of isoform AKR1C3 over AKR1C2
3-[[4-(trifluoromethyl)phenyl]amino]benzoic acid
3a-phenyl-2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-one
-
inhibitor shows 17fold and 30fold selectivity against isoforms AKR1C2 and AKR1C1, respectively, and much higher selectivity against AKR1C4
4'-hydroxyflavanone
-
-
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
5-bromo-2-[[(3-hydroxyphenyl)carbonyl]amino]benzoic acid
-
-
5-chloro-2-[[(3-hydroxyphenyl)carbonyl]amino]benzoic acid
-
-
5-hydroxyflavone
-
-
5beta-Pregnan-3beta-ol-20-one
-
-
6alpha-Methylprednisolone
-
-
7-hydroxyflavone
-
very potent inhibitor, 0.02 mM inhibits by 82.5%
9-(phenylcarbonyl)-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one
-
competitive
acetaminophen
-
non-competitive, only androsterone oxidation, pH 7.0
acetylenic ketones
-
inactivation by forming Michael adducts with enzyme nucleophiles
-
apigenin
-
0.02 mM inhibits by ca. 50%
arachidonic acid
-
-
aspirin
-
salicylate, non-competitive, only androsterone oxidation, pH 7.0
Betamethasone
-
non-competitive
cacodylate
-
-
celecoxib
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.050 mM in fluorometric assay, in vitro IC50: 0.050 mM in fluorometric assay
chlorogenic acid
-
-
Cibacron blue
-
nucleotide analog, competitive with respect to NADP+, noncompetitive to androsterone
cortisol
-
competitive
cortisone
-
competitive
Cu2+
-
100% inhibition at 0.1 mM
D-glucose 6-phosphate
-
-
dexamethasone
DMSO
-
33% inhibition
epigallocatechin gallate
-
-
Flufenamic acid
Hexestrol
Ibuprofen
indomethacin
iodoacetate
-
50% inhibition at 0.1 mM
isovitexin
-
-
Ketamine
-
specific inhibitor for AKR1C17, but no inhibition of AKR1C9
luteolin
-
0.02 mM inhibits by ca. 50%
Meclofenamic acid
Medroxyprogesterone acetate
-
-
Mefenamic acid
-
wild-type, W86Y and W227Y
NADH
-
the products, 4-androstene-3,17-dione and NADH, inhibit the activity uncompetitively and competitively, respectively, with respect to NAD+ in the presence of a saturated concentration of 0.004 mM of the substrate
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
naringenin
-
very potent inhibitor, 0.02 mM inhibits by 71.9%
non-steroidal anti-inflamatory drug
Oxyphenybutazone
-
competitive
p-chloromercuribenzenesulfonate
-
-
p-chloromercuribenzoate
Phenolphthalein
-
AKR1C4-selective inhibitor, in vitro and in vivo inhibition, IC50: 0.0004 mM
Ponalrestat
-
wild-type, W86Y and W227Y, weak inhibitor
Prednisolone
-
competitive
Prednisone
-
competitive
progesterone
-
competitive to testosterone
Prostaglandin
prostaglandin A1
-
-
prostaglandin A2alpha
-
-
Prostaglandin B1
-
-
prostaglandin E1
-
-
prostaglandin F1alpha
-
-
pyrazole
-
10% at 0.4 mM
quercetin
-
0.02 mM inhibits by ca. 50%
salicylate
-
non-competitive
silibinin
-
0.02 mM inhibits by ca. 50%
stilboestrol
-
-
testosterone
Tolmetin
-
competitive, only androsterone oxidation, pH 7.0
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
vitexin
-
-
Zomepirac
-
competitive, only androsterone oxidation, pH 7.0
zopolrestat
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
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
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0027
(5beta,20R)-20-hydroxypregnan-3-one
-
pH 7.4, 25C, recombinant wild-type AKR1C17
0.0012 - 0.726
17beta-hydroxy-5alpha-androstan-3-one
3.54 - 33.7
2-decalone
-
-
0.0031
3alpha-androstanediol
-
pH 7.0, 25C, recombinant enzyme
0.0013 - 0.408
3alpha-hydroxy-5alpha-androstan-17-one
0.163 - 0.211
4-nitrobenzyldehyde
-
-
-
0.0031
4-oxo-2-nonenal
-
pH 7.4, 25C
0.0011 - 0.0304
5alpha-Androstan-3,17-dione
0.00008 - 0.00065
5alpha-androstane-3,17-dione
0.781 - 7.331
5alpha-androstane-3alpha,17beta-diol
0.0013 - 0.012
5alpha-dihydrotestosterone
0.0021
5beta-androstane-3,17-dione
-
pH 7.4, 25C, recombinant wild-type AKR1C17
0.01
5beta-pregnane-17alpha,20beta,21-triol-3,11-dione
-
-
0.0024
5beta-pregnane-3,20-dione
-
pH 7.4, 25C, recombinant wild-type AKR1C17
0.023
6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one
-
pH 7.4, 25C, recombinant wild-type AKR1C17
0.00122 - 0.038
9,10-phenanthrenequinone
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
0.00044 - 0.1
androsterone
0.004
Dehydrolithocholic acid
-
pH 7.4, 25C, recombinant wild-type AKR1C17
0.42
diacetyl
-
pH 7.4, 25C, recombinant wild-type AKR1C17
0.022
isatin
-
pH 7.4, 25C, recombinant wild-type AKR1C17
0.004 - 0.94
NAD+
0.0057 - 0.033
NADH
0.0026 - 0.1515
NADP+
0.00016 - 0.0081
NADPH
0.0001
Prostaglandin
-
-
additional information
(11S,12S)-11,12-dihydrobenzo[g]chrysene-11,12-diol
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00063 - 0.85
(2Z)-2-(5-hydroxy-4,6-dimethyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-N,N-di(prop-2-en-1-yl)hydrazinecarbothioamide
0.115
(5beta,20R)-20-hydroxypregnan-3-one
Rattus norvegicus
-
pH 7.4, 25C, recombinant wild-type AKR1C17
0.008
3alpha-androstanediol
Homo sapiens
-
pH 7.0, 25C, recombinant enzyme
1.13 - 1.25
3alpha-hydroxy-5alpha-androstan-17-one
0.148
4-oxo-2-nonenal
Homo sapiens
-
pH 7.4, 25C
0.35
5alpha-androstan-17beta-ol-3-one
Mesocricetus auratus
-
-
0.267 - 0.567
5alpha-Androstan-3,17-dione
1.33
5alpha-androstan-3alpha,17beta-diol
Mesocricetus auratus
-
-
2.72
5alpha-Androstan-3alpha-ol-17-one
Mesocricetus auratus
-
-
0.42
5alpha-androstane-3,17-dione
Rattus norvegicus
-
pH 7.0, 25, reduction reaction
0.037 - 0.43
5alpha-dihydroprogesterone
0.033 - 1339
5alpha-dihydrotestosterone
0.767
5alpha-pregnan-21-ol-3,20-one
Mesocricetus auratus
-
-
0.233
5alpha-Pregnan-3alpha,21-diol-20-one
Mesocricetus auratus
-
-
0.45
5beta-androstan-3,17-dione
Mesocricetus auratus
-
-
1.2
5beta-Androstan-3alpha,17beta-diol
Mesocricetus auratus
-
-
1.33
5beta-Androstan-3alpha-ol-17-one
Mesocricetus auratus
-
-
0.047
5beta-androstane-3,17-dione
Rattus norvegicus
-
pH 7.4, 25C, recombinant wild-type AKR1C17
0.433
5beta-Dihydrocortisone
Mesocricetus auratus
-
-
0.417
5beta-pregnan-3,20-dione
Mesocricetus auratus
-
-
0.633
5beta-Pregnan-3alpha,21-diol-20-one
Mesocricetus auratus
-
-
0.767
5beta-Pregnan-3alpha-ol-20-one
Mesocricetus auratus
-
-
0.105
5beta-pregnane-3,20-dione
Rattus norvegicus
-
pH 7.4, 25C, recombinant wild-type AKR1C17
0.1
6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one
Rattus norvegicus
-
pH 7.4, 25C, recombinant wild-type AKR1C17
0.183 - 3.93
9,10-phenanthrenequinone
0.0028 - 318
androsterone
0.022 - 0.733
Dehydrolithocholic acid
0.167
diacetyl
Rattus norvegicus
-
pH 7.4, 25C, recombinant wild-type AKR1C17
0.2
glycochenodeoxycholic acid
Mesocricetus auratus
-
-
0.233
glycolithocholic acid
Mesocricetus auratus
-
-
0.283
isatin
Rattus norvegicus
-
pH 7.4, 25C, recombinant wild-type AKR1C17
0.217
lithocholic acid
Mesocricetus auratus
-
-
1.13 - 1.43
NAD+
0.283 - 0.367
NADH
additional information
additional information
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
47.8
4-oxo-2-nonenal
Homo sapiens
-
pH 7.4, 25C
10426
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000107
2-(2,4-dioxo-1,3-thiazolidin-5-yl)-N-(2-hydroxyphenyl)acetamide
-
pH 7.0, temperature not specified in the publication
0.00273
3a-phenyl-2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-one
-
pH 7.0, temperature not specified in the publication
0.0022 - 0.018
4-androstene-3,17-dione
0.0075
6alpha-Methylprednisolone
-
androsterone oxidation
0.006
arachidonic acid
0.65
aspirin
-
for androsterone oxidation
0.0045
Betamethasone
-
androsterone oxidation
0.00001 - 0.0005
Cibacron blue
0.19
cortisol
-
androsterone oxidation
0.285
cortisone
-
androsterone oxidation
0.01
dexamethasone
-
androsterone oxidation
0.0029 - 0.0031
Hexestrol
0.0002 - 0.001
indomethacin
0.017
NADH
-
-
0.0175
Prednisolone
0.0031
prostaglandin A1
-
androsterone oxidation
0.003
prostaglandin A2alpha
-
-
0.0008
Prostaglandin B1
-
androsterone oxidation
0.0075
prostaglandin E1
-
androsterone oxidation
0.012
prostaglandin F1alpha
-
androsterone oxidation
0.115 - 0.75
salicylate
-
-
additional information
additional information
-
more Ki values given for different inhibitors of androsterone oxidation, 9,10-phenanthrenequinone- and 5alpha-androstane-3,17-dione reduction
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0136
(2E)-3-(4-bromophenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
0.0134
(2E)-3-(4-methylphenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.0058
(2E)-3-[4-(methylsulfanyl)phenyl]-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.000094
1-(4-[[(2R)-2-methylpiperidin-1-yl]sulfonyl]phenyl)-1,3-dihydro-2H-pyrrol-2-one
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.000056
1-(4-[[(2R,6S)-2,6-dimethylpiperidin-1-yl]sulfonyl]phenyl)pyrrolidin-2-one
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.000052
1-[4-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)phenyl]pyrrolidin-2-one
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.0003
2'-hydroxyflavanone
Homo sapiens
-
-
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
0.0049
7-hydroxyflavone
Homo sapiens
-
-
0.0218
apigenin
Homo sapiens
-
-
0.05
celecoxib
Homo sapiens
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.050 mM in fluorometric assay, in vitro IC50: 0.050 mM in fluorometric assay
0.00031 - 1.084
Flufenamic acid
0.009
Ibuprofen
Homo sapiens
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.017 mM in fluorometric assay, in vitro IC50: 0.009 mM in fluorometric assay
0.000735 - 0.00333
indomethacin
0.0374
luteolin
Homo sapiens
-
-
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
0.0024
naringenin
Homo sapiens
-
-
0.0004
Phenolphthalein
Homo sapiens
-
AKR1C4-selective inhibitor, in vitro and in vivo inhibition, IC50: 0.0004 mM
0.0188
quercetin
Homo sapiens
-
-
0.0062
silibinin
Homo sapiens
-
-
0.000049
ursodeoxycholate
Homo sapiens
-
natural inhibitor, in vivo IC50: 0.00024 mM in fluorometric assay, 0.00014 mM in radiometric assay, in vitro IC50: 0.000049 mM in fluorometric assay
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0005 - 0.0053
-
for prostaglandins A1, A2, B1, B2, D2, E1, E2, F1, F2alpha at concentrations of 0.06 mM
0.0007 - 0.0012
-
for 15-keto-prostaglandins E2 and F2alpha at concentrations of 0.06 mM
0.006
-
purified recombinant mutant W227A, substrate androsterone
0.008 - 4
-
determined for several substrates,with best activities for 9,10-phenanthrenequinone, 4-nitrobezaldehyde and androsterone
0.01
-
purified recombinant mutant F118A, substrate androsterone
0.03
-
purified recombinant mutant F129A, substrate androsterone
0.059
-
W86Y mutant
0.07
-
recombinant AKR1C17 in cell extract, substrate 4-androsten-3alpha-ol-17-one
0.09
-
purified recombinant mutant N306A, substrate androsterone
0.23
-
purified recombinant AKR1C17, substrate 4-androsten-3alpha-ol-17-one
0.674
-
W148Y mutant
0.71
-
NADP+ dependent
0.81
-
Y216S mutant, androsterone oxidation with NADP+
0.86
-
purified recombinant mutant T24A, substrate androsterone
0.96
-
purified recombinant mutant T226A, substrate androsterone
1.5
-
native enzyme
1.55
-
recombinant wild type enzyme, androsterone oxidation with NAD+
2
-
for androsterone
4.2
-
NAD+ dependent
26.8 - 375
-
liver
9540
-
purified enzyme
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4 - 9.5
-
recombinant enzyme
7.5
-
assay at
10.4
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 11
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
the enzyme expression is positively correlated to adiposity in woman
Manually annotated by BRENDA team
-
high expression and activity in astrocytes of glaucomatous optic nerve head
Manually annotated by BRENDA team
-
uniform, diffuse, and strong expression of isoform AKR1C3 in normal endometrial epithelium but not in endometrial stromal cells. The expression of AKR1C3 is reduced in both hyperplastic and carcinomatous endometrial epithelium
Manually annotated by BRENDA team
-
uniform, diffuse, and strong expression of isoform AKR1C3 in normal endometrial epithelium but not in endometrial stromal cells. The expression of AKR1C3 is reduced in both hyperplastic and carcinomatous endometrial epithelium
Manually annotated by BRENDA team
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
Manually annotated by BRENDA team
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
Manually annotated by BRENDA team
-
strong isoform AKR1C3 immunoreactivity in columnar epithelium but only weak immunoreactivity in squamous epithelium of the gastrointestinal junction
Manually annotated by BRENDA team
-
primary, high expression and activity in healthy hepatocytes
Manually annotated by BRENDA team
-
strong isoform AKR1C3 immunoreactivity in bronchial epithelium but not in bronchial glands or alveolar pneumocytes
Manually annotated by BRENDA team
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
Manually annotated by BRENDA team
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
Manually annotated by BRENDA team
-
6fold higher expression level in female than in male pituitary
Manually annotated by BRENDA team
-
lumbar, of naive, sham-operated and neuropathic rats, enzyme expression analysis and cellular distribution in neurons and glial cells, immunohistochemic analysis, overview
Manually annotated by BRENDA team
-
abundant enzyme expression
Manually annotated by BRENDA team
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
27000
-
PAGE, western blot
34600
-
gel filtration
35000
-
gel filtration
36000
-
recombinant AKR1C17, gel filtration
37030
-
predicted molecular weight from the cDNA
74000 - 75000
-
native PAGE, kidney enzyme
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
tetramer
additional information
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, 4C, 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, 4C, 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
-
vapor diffusion techniques using ammonium sulfate as precipitant
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-10C, 3 weeks, activity declines about 50%
-
-10C, most purified preparation, 5 days, loses between 80% and 100% of activity
-
-70C, 20 mM potassium phosphate buffer, pH 7.0, 1 mM EDTA, 1 mM beta-mercaptoethanol, 30% glycerol
-
-80C, 20 mM potassium phosphate buffer, pH 7.0, 1 mM EDTA, 1 mM DTT, 30% glycerol
-
3C, first ammonium sulfate fraction, stable at least 3 weeks
-
3C, most purified preparation, 5 days, loses 50% of activity
-
4C, 10 mM-Tris/HCl, pH 8.0, 5 mM 2-mercaptoethanol, 0.5 mM EDTA, 20% glycerol
-
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
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anion exchange and Blue Sepharose column
-
anion exchange and Blue Sepharose column; N167A chromatofocusing and gel filtration introduced between the to others chromatography steps
-
CaCl2 and ammonium sulfate fractionation, DEAE-cellulose- and hydroxyapatite chromatography, chromatofocusing, Sephadex G-100
-
Centriprep-10 concentration, DEAE-HPLC
-
native enzyme 73.3fold from liver by ammonium sulfate, anion-exchange chromatography, gel filtration, and affinity chromatography
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purification of recombinant wild type and mutants of AKR1C9
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recombinant enzyme from Escherichia coli strain C41(DE3) in a successive chromatographic procedure, to homogeneity
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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
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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
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recombinant wild-type and mutant AKR1C17s from Escherichia coli strain BL21(DE3)
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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)
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chromosomal localization is 10q15-q14, phylogenetic tree
-
DNA and amino acid sequence analysis and comparison
-
expression and promoter activity analysis, genetic enzyme regulation, overview
-
expression in Cos-1 cells
-
expression in Escherichia coli
-
expression of His-tagged wild-type and mutant enzymes in Escherichia coli
-
expression of recombinant wild type and mutants of AKR1C9
-
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)
-
full-length cDNA gene is expressed in Escherichia coli DH5alpha
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overexpressed in Escherichia coli HMS174(DE3)
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overexpression in Escherichia coli strain C41(DE3)
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overexpression of AKR1C9 in Escherichia coli
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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)
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overexpression of wild-type and mutant enzymes in Escherichia coli C41(DE3)
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plasmid DNA containing cDNA is transformed in Escherichia coli HB101, cDNA is used for sequencing
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stable expression of wild-type and mutant enzymes in HEK-293 cells
-
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
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the expression of isoform AKR1C3 is reduced in both hyperplastic and carcinomatous endometrial epithelium
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
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
H117A
-
1/500th catalytic efficiency of wild type, unlikely to be the general amino acid for catalysis
K84M
-
inactive, unable to bind steroids
K84R
-
inactive, unable to bind steroids
N167A
-
site-directed mutagenesis, most impaired enzyme
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
S166A
-
site-directed mutagenesis, decreased binding affinity to NADP(H), only binding of cofactor is affected, residue is located at the catalytic center
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
Y55F
-
inactive, unable to perform steroid oxidoreduction, strongest candidate for the general amino acid
Y55S
-
inactive, strongest candidate for the general amino acid
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
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