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Information on EC 1.1.1.357 - 3alpha-hydroxysteroid 3-dehydrogenase
for references in articles please use BRENDA:EC1.1.1.357
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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
1.1.1.357 3alpha-hydroxysteroid 3-dehydrogenase
IUBMB Comments
The enzyme acts on multiple 3α-hydroxysteroids, such as androsterone and 5 α-dihydrotestosterone. The mammalian enzymes are involved in inactivation of steroid hormones, while the bacterial enzymes are involved in steroid degradation. This entry stands for enzymes whose stereo-specificity with respect to NAD+ or NADP+ is not known. [cf. EC 1.1.1.50, 3α-hydroxysteroid 3-dehydrogenase (Si-specific) and EC 1.1.1.213, 3α-hydroxysteroid 3-dehydrogenase (Re-specific)].
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
- 1.1.1.357
- ileal
-
ibabp
-
farnesoid
-
enterohepatic
- akr1c2
- 3alpha-hydroxysteroids
- glycocholate
- 3alpha-hsds
- gcda
- glycochenodeoxycholate
- drug development
showSynonyms
bile acid binding protein, aldo-keto reductase family 1 member c3, akr1c33, 3alpha-hsd type iii, aldo-keto reductase family 1 member c2, type 1 3alpha-hsd, 3alpha-hydroxysteroid dehydrogenase type iii, hsd 28, dihydrodiol dehydrogenase 4, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
3alpha-HSD
3alpha-HSD/CR
3alpha-HSD3
3alpha-HSOR
3alpha-hydroxysteroid dehydrogenase
3alpha-hydroxysteroid dehydrogenase/carbonyl reductase
3alpha-hydroxysteroid oxidoreductase
AKR1C14
AKR1C2
AKR1C4
DD2
HSD 28
type 3 3alpha-hydroxysteroid dehydrogenase
type I 3alpha-HSD
3alpha-hydroxysteroid dehydrogenase/carbonyl reductase
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
-
-
-
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
the reaction catalyzed by the enzyme shows an ordered bi bi kinetic mechanism with NAD+ being the first substrate to be bound and NADH the last product to be released. The rate-limiting steps along the reaction pathway is the release of NADH for reaction with andosterone or androsterol, while the hydride transfer for 2-decalol is rate limiting for the overall reaction. Structure of the transition state by measuring the rate constant of a reaction upon substitution of a heavy atom for a light one at or adjacent to the bond cleavage during the reaction
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
rate-limiting step in the reaction is the release of NADH and proton. P185, T188 and the flexible substrate-binding loop are involved in binding with the nucleotide cofactor and with androsterone and are also involved in catalysis, catalytic mechanism, overview
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
rapid equilibrium ordered bi bi kinetic mechanism
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PATHWAY SOURCE
PATHWAYS
MetaCyc
brassinolide biosynthesis I, brassinolide biosynthesis II, testosterone and androsterone degradation to androstendione (aerobic)
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SYSTEMATIC NAME
IUBMB Comments
3alpha-hydroxysteroid:NAD(P)+ 3-oxidoreductase
The enzyme acts on multiple 3alpha-hydroxysteroids, such as androsterone and 5 alpha-dihydrotestosterone. The mammalian enzymes are involved in inactivation of steroid hormones, while the bacterial enzymes are involved in steroid degradation. This entry stands for enzymes whose stereo-specificity with respect to NAD+ or NADP+ is not known. [cf. EC 1.1.1.50, 3alpha-hydroxysteroid 3-dehydrogenase (Si-specific) and EC 1.1.1.213, 3alpha-hydroxysteroid 3-dehydrogenase (Re-specific)].
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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
(S)-1,2,3,4-tetrahydronaphth-1-ol + NADP+
1,2,3,4-tetrahydronaphth-1-one + NADPH + H+
-
Substrates: -
Products: -
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?
(S)-indan-1-ol + NADP+
indan-1-one + NADPH + H+
-
Substrates: -
Products: -
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?
1-acenaphthenol + NADP+
acenaphthylen-1(2H)-one + NADPH + H+
Substrates: -
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?
17beta-estradiol + NAD(P)H + H+
estrone + NAD(P)+
Substrates: -
Products: -
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?
2-(1-imidazolyl)-1-(4-methoxyphenyl)-2-methyl-1-propanone + NAD(P)H + H+
2-(1H-imidazol-1-yl)-1-(4-methoxyphenyl)-2-methylpropan-1-ol + NAD(P)+
Substrates: 2-(1-imidazolyl)-1-(4-methoxyphenyl)-2-methyl-1-propanone i.e. NKI 42255
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?
2-decalol + NAD+
2-decalone + NADH + H+
Substrates: -
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r
2-decalol + NAD+
2-decanone + NADH + H+
Substrates: -
Products: -
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r
20alpha-hydroxyprogesterone + NAD(P)H + H+
progesterone + NAD(P)+
Substrates: -
Products: -
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?
3-dehydro-beta-ecdysone + NAD(P)H + H+
beta-ecdysone + NAD(P)+
Substrates: -
Products: -
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?
3alpha-androstanediol + NAD(P)+
5alpha-dihydrotestosterone + NAD(P)H + H+
Substrates: -
Products: -
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r
3alpha-androstanediol + NAD+
5alpha-dihydrotestosterone + NADH + H+
-
Substrates: -
Products: -
Products: -
?
4-androstenedione + NADPH
?
Substrates: the enzyme act as reductase for 4-hydroxyandrostenedione in both COS-1 cells and in reaction systems with purified enzymes. It exerts 3alpha-, 3beta-, and 17beta-hydroxysteroid dehydrogenase activities
Products: -
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?
4-hydroxyandrostenedione + NADPH + H+
3alpha,4beta-dihydroxy-5alpha-androstan-17-one + NADP+
Substrates: -
Products: -
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?
4-hydroxytestosterone + NADPH + H+
3alpha,4beta-dihydroxy-5alpha-androstan-17-ol + NADP+
Substrates: -
Products: -
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?
5alpha-androstan-17-beta-ol-3-one + NADH + H+
5alpha-androstane-3alpha,17beta-diol + NAD+
Substrates: NADH is not a substrate for wild-type
Products: -
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r
5alpha-androstan-17-beta-ol-3-one + NADPH + H+
5alpha-androstane-3alpha,17beta-diol + NADP+
Substrates: -
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r
5alpha-androstan-3alpha-ol-17-one + NADP+
(5alpha)-androstan-3,17-dione + NADPH + H+
-
Substrates: -
Products: -
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?
5alpha-androstane-3,17-dione + NAD(P)H + H+
androsterone + NAD(P)+
Substrates: -
Products: -
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?
5alpha-androstane-3alpha,17beta-diol + NAD+
5alpha-androstan-17-beta-ol-3-one + NADH + H+
Substrates: -
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r
5alpha-androstane-3alpha,17beta-diol + NADP+
(5alpha)-androstan-17-beta-ol-3-one + NADPH + H+
-
Substrates: -
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?
5alpha-androstane-3alpha,17beta-diol + NADP+
5alpha-androstan-17-beta-ol-3-one + NADPH + H+
Substrates: -
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r
5alpha-dihydroprogesterone + NADPH + H+
allopregnanolone + 5alpha,20alpha-tetrahydroprogesterone + NADP+
Substrates: -
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r
5alpha-pregnan-20alpha-ol-3-one + NADP+
5alpha-pregnane-3,20-dione + NADPH + H+
Substrates: -
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r
5beta-androstan-3,17-dione + NADPH + H+
5beta-androstan-3alpha-ol-17-one + NADP+
Substrates: -
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r
5beta-androstan-3alpha-ol-17-one + NADP+
(5beta)-androstan-3,17-dione + NADPH + H+
-
Substrates: -
Products: -
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?
5beta-androstan-3alpha-ol-17-one + NADP+
5beta-androstan-3,17-dione + NADPH + H+
Substrates: -
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r
5beta-androstane-3alpha,17beta-diol + NADP+
5beta-androstan-17beta-ol-3-one + NADPH + H+
-
Substrates: -
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?
5beta-dihydroprogesterone + NADPH + H+
pregnanolone + NADP+
Substrates: -
Products: -
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r
5beta-pregnane-3,20-dione + NADPH + H+
5beta-pregnan-20alpha-ol-3-one + NADP+
Substrates: -
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r
5beta-pregnane-3alpha,20alpha-diol + NADP+
(5beta)-pregnan-20alpha-ol-3-one + NADPH + H+
-
Substrates: -
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?
7alpha,12alpha-dihydroxy-5beta-cholestan-3-one + NAD(P)+
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestane + NAD(P)H + H+
-
Substrates: -
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?
9alpha,11beta-prostaglandin F2 + NADP+
? + NADPH + H+
-
Substrates: -
Products: -
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?
a 3-alpha-hydroxysteroid + NAD(P)+
a 3-oxosteroid + NAD(P)H + H+
Substrates: -
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?
allopregnanolone + 5alpha,20alpha-tetrahydroprogesterone + NADP+
5alpha-dihydroprogesterone + NADPH + H+
Substrates: -
Products: -
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r
androstandiol + NAD(P)+
(5alpha,17beta)-17-hydroxyandrostan-3-one + NAD(P)H + H+
Substrates: -
Products: -
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?
androstenol + NAD+
5alpha-androst-16-en-3-one + NADH + H+
Substrates: -
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r
androsterone + NAD(P)+
5alpha-androstane-3,17-dione + NAD(P)H + H+
Substrates: -
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?
androsterone + NAD+
(5alpha)-androstane-3,17-dione + NADH + H+
-
Substrates: -
Products: -
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?
androsterone + NAD+
androstanedione + NADH + H+
Substrates: -
Products: -
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r
androsterone + NADP+
(5alpha)-androstane-3,17-dione + NADPH + H+
-
Substrates: -
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?
androsterone + NADP+
5alpha-androstane-3,17-dione + NADPH + H+
Substrates: -
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?
chenodeoxycholic acid + NADP+
(5beta,7alpha,8xi)-7-hydroxy-3-oxocholan-24-oic acid + NADPH + H+
Substrates: -
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?
cholate + NAD+
7alpha,12alpha-dihydroxy-3-oxo-5beta-cholan-24-oic acid + NADH + H+
Substrates: -
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r
cholic acid + NAD(P)+
(5beta,7alpha,8xi,12alpha)-7,12-dihydroxy-3-oxocholan-24-oic acid + NAD(P)H + H+
cholic acid + NAD+
dehydrocholic acid + NADH + H+
-
Substrates: -
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r
cyclohexanol + NAD+
cyclohexanone + NADH + H+
Substrates: -
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r
dehydrocholic acid + NADH + H+
cholic acid + NAD+
-
Substrates: -
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r
dehydrolithocholic acid + NADPH + H+
?
Substrates: -
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r
deoxycholic acid + NADH
12alpha-hydroxy-3-oxo-5beta-cholan-24-oic acid + NAD+
Substrates: -
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r
dihydrotestosterone + NAD(P)H + H+
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
Substrates: -
Products: -
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?
epiandrosterone + NAD(P)+
(5alpha)-androstane-3,17-dione + NAD(P)H + H+
Substrates: -
Products: -
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?
estrone + NAD(P)H + H+
17beta-estradiol + NAD(P)+
Substrates: -
Products: -
Products: -
?
fusidic acid + NAD(P)+
(2Z)-2-[(4alpha,5alpha,8alpha,9beta,11alpha,13alpha,14beta,16beta,17Z)-16-(acetyloxy)-11-hydroxy-4,8,10,14-tetramethyl-3-oxogonan-17-ylidene]-6-methylhept-5-enoic acid + NAD(P)H + H+
fusidic acid + NADP+
(2Z)-2-[(4alpha,5alpha,8alpha,9beta,11alpha,13alpha,14beta,16beta,17Z)-16-(acetyloxy)-11-hydroxy-4,8,10,14-tetramethyl-3-oxogonan-17-ylidene]-6-methylhept-5-enoic acid + NADPH + H+
metyrapol + NAD(P)+
2-methyl-1,2-di(pyridin-3-yl)propan-1-one + NAD(P)H + H+
Substrates: -
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?
pregn-4-en-3,20-dione + NADPH + H+
3alpha-hydroxypregn-4-en-20-one + NADP+
Substrates: -
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r
progesterone + NAD(P)H + H+
20alpha-hydroxyprogesterone + NAD(P)+
Substrates: -
Products: -
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?
testosterone + NAD(P)H + H+
DELTA4-androstene-3,17-dione + NAD(P)+
Substrates: -
Products: -
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?
testosterone + NADPH + H+
?
Substrates: the enzyme act as reductase for 4-hydroxyandrostenedione in both COS-1 cells and in reaction systems with purified enzymes. It exerts 3alpha-, 3beta-, and 17beta-hydroxysteroid dehydrogenase activities
Products: -
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?
3-dehydro-alpha-ecdysone + NAD(P)H + H+
alpha-ecdysone + NAD(P)+
Substrates: -
Products: -
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?
3-dehydro-alpha-ecdysone + NAD(P)H + H+
alpha-ecdysone + NAD(P)+
Substrates: -
Products: -
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?
3-dehydro-alpha-ecdysone + NAD(P)H + H+
alpha-ecdysone + NAD(P)+
Substrates: -
Products: -
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?
3alpha-hydroxydesogestrel + NAD(P)+
3-oxodesogestrel + NAD(P)H + H+
Substrates: -
Products: -
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?
3alpha-hydroxydesogestrel + NAD(P)+
3-oxodesogestrel + NAD(P)H + H+
Substrates: -
Products: -
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?
4-hydroxyandrostenedione + NADPH
?
Substrates: the enzyme act as reductase for 4-hydroxyandrostenedione in both COS-1 cells and in reaction systems with purified enzymes. It exerts 3alpha-, 3beta-, and 17beta-hydroxysteroid dehydrogenase activities
Products: -
Products: -
?
4-hydroxyandrostenedione + NADPH
?
Substrates: the enzyme act as reductase for 4-hydroxandrostenedione in both COS-1 cells and in reaction systems with purified enzymes. It exerts 3alpha-, 3beta-, and 17beta-hydroxysteroid dehydrogenase activities
Products: -
Products: -
?
4-hydroxytestosterone + NADPH
?
Substrates: the enzyme act as reductase for 4-hydroxyandrostenedione in both COS-1 cells and in reaction systems with purified enzymes. It exerts 3alpha-, 3beta-, and 17beta-hydroxysteroid dehydrogenase activities
Products: -
Products: -
?
4-hydroxytestosterone + NADPH
?
Substrates: the enzyme act as reductase for 4-hydroxandrostenedione in both COS-1 cells and in reaction systems with purified enzymes. It exerts 3alpha-, 3beta-, and 17beta-hydroxysteroid dehydrogenase activities
Products: -
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?
4-nitroacetophenone + NAD(P)H + H+
1-(4-nitrophenyl)ethanol + NAD(P)+
Substrates: -
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?
4-nitroacetophenone + NAD(P)H + H+
1-(4-nitrophenyl)ethanol + NAD(P)+
Substrates: -
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?
4-nitrobenzaldehyde + NAD(P)H + H+
(4-nitrophenyl)methanol + NAD(P)+
Substrates: -
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?
4-nitrobenzaldehyde + NAD(P)H + H+
(4-nitrophenyl)methanol + NAD(P)+
Substrates: -
Products: -
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?
5alpha-dihydroprogesterone + NADPH + H+
5alpha,20alpha-tetrahydroprogesterone + NADP+
Substrates: reaction of EC 1.1.1.149
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5alpha-dihydroprogesterone + NADPH + H+
5alpha,20alpha-tetrahydroprogesterone + NADP+
Substrates: reaction of EC 1.1.1.149
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5alpha-dihydroprogesterone + NADPH + H+
5alpha,20alpha-tetrahydroprogesterone + NADP+
Substrates: reaction of EC 1.1.1.149
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r
5alpha-dihydrotestosterone + NAD(P)H + H+
(5alpha,17beta)-androstane-3,17-diol + NAD(P)+
Substrates: -
Products: -
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?
5alpha-dihydrotestosterone + NAD(P)H + H+
(5alpha,17beta)-androstane-3,17-diol + NAD(P)+
Substrates: -
Products: -
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?
5alpha-dihydrotestosterone + NAD(P)H + H+
(5alpha,17beta)-androstane-3,17-diol + NAD(P)+
Substrates: -
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?
5alpha-dihydrotestosterone + NAD(P)H + H+
3alpha-androstanediol + NAD(P)+
Substrates: -
Products: -
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r
5alpha-dihydrotestosterone + NAD(P)H + H+
3alpha-androstanediol + NAD(P)+
-
Substrates: -
Products: -
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?
5alpha-dihydrotestosterone + NADPH + H+
3alpha-androstanediol + NADP+
-
Substrates: -
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?
5alpha-dihydrotestosterone + NADPH + H+
3alpha-androstanediol + NADP+
Substrates: physiological inactivation of the most potent androgen 5alpha dihydrotestosterone
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5alpha-dihydrotestosterone + NADPH + H+
3alpha-androstanediol + NADP+
Substrates: -
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r
5alpha-dihydrotestosterone + NADPH + H+
5alpha-androstane-3alpha,17beta-diol + NADP+
Substrates: -
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r
5alpha-dihydrotestosterone + NADPH + H+
5alpha-androstane-3alpha,17beta-diol + NADP+
Substrates: -
Products: -
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r
5beta-dihydrotestosterone + NAD(P)H + H+
(5beta,17beta)-androstane-3,17-diol + NAD(P)+
Substrates: -
Products: -
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?
5beta-dihydrotestosterone + NAD(P)H + H+
(5beta,17beta)-androstane-3,17-diol + NAD(P)+
Substrates: -
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?
5beta-dihydrotestosterone + NAD(P)H + H+
(5beta,17beta)-androstane-3,17-diol + NAD(P)+
Substrates: -
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?
a 3alpha-hydroxysteroid + NAD(P)+
a 3-oxosteroid + NAD(P)H + H+
Substrates: -
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?
a 3alpha-hydroxysteroid + NAD(P)+
a 3-oxosteroid + NAD(P)H + H+
Substrates: -
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a 3alpha-hydroxysteroid + NAD(P)+
a 3-oxosteroid + NAD(P)H + H+
Substrates: -
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a 3alpha-hydroxysteroid + NAD(P)+
a 3-oxosteroid + NAD(P)H + H+
Substrates: -
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a 3alpha-hydroxysteroid + NAD+
a 3-oxosteroid + NADH + H+
Substrates: -
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a 3alpha-hydroxysteroid + NAD+
a 3-oxosteroid + NADH + H+
Substrates: -
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a 3alpha-hydroxysteroid + NAD+
a 3-oxosteroid + NADH + H+
Substrates: -
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androstandione + NAD(P)H + H+
3-hydroxyandrostan-17-one + NAD(P)+
Substrates: -
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?
androstandione + NAD(P)H + H+
3-hydroxyandrostan-17-one + NAD(P)+
Substrates: -
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?
androsterone + NAD(P)+
(5alpha)-androstane-3,17-dione + NAD(P)H + H+
Substrates: -
Products: -
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?
androsterone + NAD(P)+
(5alpha)-androstane-3,17-dione + NAD(P)H + H+
Substrates: -
Products: -
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?
androsterone + NAD+
5alpha-androstan-3,17-dione + NADH + H+
Substrates: -
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r
androsterone + NAD+
5alpha-androstan-3,17-dione + NADH + H+
Substrates: rate-limiting step in the reaction is the release of NADH
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r
cholic acid + NAD(P)+
(5beta,7alpha,8xi,12alpha)-7,12-dihydroxy-3-oxocholan-24-oic acid + NAD(P)H + H+
Substrates: -
Products: -
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?
cholic acid + NAD(P)+
(5beta,7alpha,8xi,12alpha)-7,12-dihydroxy-3-oxocholan-24-oic acid + NAD(P)H + H+
Substrates: -
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?
dihydroprogesterone + NADPH + H+
allopregnanolone + NADP+
Substrates: -
Products: -
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?
dihydroprogesterone + NADPH + H+
allopregnanolone + NADP+
-
Substrates: -
Products: -
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?
dihydrotestosterone + NADPH
?
Substrates: the enzyme act as reductase for 4-hydroxyandrostenedione in both COS-1 cells and in reaction systems with purified enzymes. It exerts 3alpha-, 3beta-, and 17beta-hydroxysteroid dehydrogenase activities
Products: -
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dihydrotestosterone + NADPH
?
Substrates: the enzyme act as reductase for 4-hydroxandrostenedione in both COS-1 cells and in reaction systems with purified enzymes. It exerts 3alpha-, 3beta-, and 17beta-hydroxysteroid dehydrogenase activities
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dihydrotestosterone + NADPH + H+
4-androsten-3alpha,17beta-diol + NADP+
Substrates: low activity
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dihydrotestosterone + NADPH + H+
4-androsten-3alpha,17beta-diol + NADP+
Substrates: high activity
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dihydrotestosterone + NADPH + H+
4-androsten-3alpha,17beta-diol + NADP+
Substrates: -
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dihydrotestosterone + NADPH + H+
4-androsten-3alpha,17beta-diol + NADP+
Substrates: -
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dihydrotestosterone + NADPH + H+
4-androsten-3alpha,17beta-diol + NADP+
Substrates: -
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dihydrotestosterone + NADPH + H+
5alpha-androstane-3alpha,17beta-diol + NADP+
Substrates: -
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?
dihydrotestosterone + NADPH + H+
5alpha-androstane-3alpha,17beta-diol + NADP+
-
Substrates: -
Products: -
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fusidic acid + NAD(P)+
(2Z)-2-[(4alpha,5alpha,8alpha,9beta,11alpha,13alpha,14beta,16beta,17Z)-16-(acetyloxy)-11-hydroxy-4,8,10,14-tetramethyl-3-oxogonan-17-ylidene]-6-methylhept-5-enoic acid + NAD(P)H + H+
Substrates: -
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?
fusidic acid + NAD(P)+
(2Z)-2-[(4alpha,5alpha,8alpha,9beta,11alpha,13alpha,14beta,16beta,17Z)-16-(acetyloxy)-11-hydroxy-4,8,10,14-tetramethyl-3-oxogonan-17-ylidene]-6-methylhept-5-enoic acid + NAD(P)H + H+
Substrates: -
Products: -
Products: -
?
fusidic acid + NADP+
(2Z)-2-[(4alpha,5alpha,8alpha,9beta,11alpha,13alpha,14beta,16beta,17Z)-16-(acetyloxy)-11-hydroxy-4,8,10,14-tetramethyl-3-oxogonan-17-ylidene]-6-methylhept-5-enoic acid + NADPH + H+
Substrates: -
Products: -
Products: -
?
fusidic acid + NADP+
(2Z)-2-[(4alpha,5alpha,8alpha,9beta,11alpha,13alpha,14beta,16beta,17Z)-16-(acetyloxy)-11-hydroxy-4,8,10,14-tetramethyl-3-oxogonan-17-ylidene]-6-methylhept-5-enoic acid + NADPH + H+
Substrates: -
Products: -
Products: -
?
metyrapone + NAD(P)H + H+
2-methyl-1,2-di(pyridin-3-yl)propan-1-ol + NAD(P)+
Substrates: -
Products: -
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?
metyrapone + NAD(P)H + H+
2-methyl-1,2-di(pyridin-3-yl)propan-1-ol + NAD(P)+
Substrates: -
Products: -
Products: -
?
additional information
?
-
Substrates: no activity with testosterone, 3-oxo-desogestrel, progesterone, 4-nitrobenzalcohol, trans-benzene dihydrodiol and cis-benzene dihydrodiol
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity with testosterone, 3-oxo-desogestrel, progesterone, 4-nitrobenzalcohol, trans-benzene dihydrodiol and cis-benzene dihydrodiol
Products: -
Products: -
?
additional information
?
-
Substrates: recombinant 3alpha-HSD/CR protein is active with a variety of C1927 steroid substrates, catalyzing the 3-oxo reduction and 3alpha-hydroxy dehydrogenation of steroids of the androstane and bile acid series with Km-values in the low micromolar range, 1842 microM
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?
additional information
?
-
Substrates: recombinant enzyme catalyzes carbonyl reduction of nonsteroidal aldehyde and ketone compounds e.g. metyrapone, 4-nitrobenzaldehyde and insecticide NKI 42255, no reverse oxidation of the formed hydroxy derivatives 4-nitrobenzalcohol and NKI 42455 observed
Products: -
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?
additional information
?
-
Substrates: no activity with testosterone and progesterone
Products: -
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?
additional information
?
-
Substrates: the enzyme catalyzes reversibly the oxidoreduction of 3alpha-hydroxyl groups of steroid hormones
Products: -
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?
additional information
?
-
Substrates: 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase catalyzes the oxidation of androsterone with NAD+ to form androstanedione and NADH with the rate-limiting step being the release of NADH in the overall reaction. No enzyme activity is detected for methanol, ethanol, and 2-propanol, which lack the steroid scaffold of androsterone, implying that the steroid scaffold plays an important role in enzyme catalytic specificity. Role of remote substrate binding interactions contributing to the rate enhancement by 3apha-HSD/CR, overview. Uniform binding improves catalysis with simple cyclic alcohols, differential binding improves catalysis of steroid substrates. Reaction product identifcation by LC-MS/MS analysis
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?
additional information
?
-
Substrates: recombinant 3alpha-HSD/CR protein is active with a variety of C1927 steroid substrates, catalyzing the 3-oxo reduction and 3alpha-hydroxy dehydrogenation of steroids of the androstane and bile acid series with Km-values in the low micromolar range, 1842 microM
Products: -
Products: -
?
additional information
?
-
Substrates: recombinant enzyme catalyzes carbonyl reduction of nonsteroidal aldehyde and ketone compounds e.g. metyrapone, 4-nitrobenzaldehyde and insecticide NKI 42255, no reverse oxidation of the formed hydroxy derivatives 4-nitrobenzalcohol and NKI 42455 observed
Products: -
Products: -
?
additional information
?
-
Substrates: no activity with testosterone and progesterone
Products: -
Products: -
?
additional information
?
-
Substrates: the enzyme catalyzes reversibly the oxidoreduction of 3alpha-hydroxyl groups of steroid hormones
Products: -
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?
additional information
?
-
-
Substrates: isoform AKR1C2 functions preferentially as a 3-ketosteroid reductase
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?
additional information
?
-
Substrates: DD2 is an isoenzyme of DD4 sharing 82% amino acid sequence identity
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?
additional information
?
-
Substrates: DD2 is an isoenzyme of DD4 sharing 82% amino acid sequence identity
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?
additional information
?
-
Substrates: DD4 is an isoenzyme of DD2 sharing 82% amino acid sequence identity
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?
additional information
?
-
Substrates: DD4 is an isoenzyme of DD2 sharing 82% amino acid sequence identity
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?
additional information
?
-
Substrates: the enzyme also exhibits a weak 17beta-hydroxysteroid dehydrogenase activity transforming androstenedione into testosterone
Products: -
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?
additional information
?
-
Substrates: identification of metabolites by GC-MSMS in feeding experiments of recombinant COS-1 cells. Substrate specificity of recombinant AKR1C isozymes, overview. The isozymes also have 17beta-hydroxysteroid dehydrogenase activity. No activity with 4-androstenedione, testosterone and poor activity with 4-hydroxytestosterone (4-OHT)
Products: -
Products: -
?
additional information
?
-
Substrates: identification of metabolites by GC-MSMS in feeding experiments of recombinant COS-1 cells. Substrate specificity of recombinant AKR1C isozymes, overview. The isozymes also have 17beta-hydroxysteroid dehydrogenase activity. No activity with 4-androstenedione, testosterone and poor activity with 4-hydroxytestosterone (4-OHT)
Products: -
Products: -
?
additional information
?
-
Substrates: identification of metabolites by GC-MSMS in feeding experiments of recombinant COS-1 cells. Substrate specificity of recombinant AKR1C isozymes, overview. The isozymes also have 17beta-hydroxysteroid dehydrogenase activity. No activity with 4-androstenedione, testosterone and poor activity with 4-hydroxytestosterone (4-OHT)
Products: -
Products: -
?
additional information
?
-
Substrates: identification of metabolites by GC-MSMS in feeding experiments of recombinant COS-1 cells. Substrate specificity of recombinant AKR1C isozymes, overview. The isozymes also have 17beta-hydroxysteroid dehydrogenase activity. No activity with 4-androstenedione, testosterone and poor activity with 4-hydroxytestosterone (4-OHT)
Products: -
Products: -
?
additional information
?
-
Substrates: identification of metabolites by GC-MSMS in feeding experiments of recombinant COS-1 cells. Substrate specificity of recombinant AKR1C isozymes, overview. The isozymes also have 17beta-hydroxysteroid dehydrogenase activity. No activity with 4-androstenedione and testosterone, and poor activity with 4-hydroxytestosterone (4-OHT)
Products: -
Products: -
?
additional information
?
-
Substrates: identification of metabolites by GC-MSMS in feeding experiments of recombinant COS-1 cells. Substrate specificity of recombinant AKR1C isozymes, overview. The isozymes also have 17beta-hydroxysteroid dehydrogenase activity. No activity with 4-androstenedione and testosterone, and poor activity with 4-hydroxytestosterone (4-OHT)
Products: -
Products: -
?
additional information
?
-
Substrates: identification of metabolites by GC-MSMS in feeding experiments of recombinant COS-1 cells. Substrate specificity of recombinant AKR1C isozymes, overview. The isozymes also have 17beta-hydroxysteroid dehydrogenase activity. No activity with 4-androstenedione and testosterone, and poor activity with 4-hydroxytestosterone (4-OHT)
Products: -
Products: -
?
additional information
?
-
Substrates: identification of metabolites by GC-MSMS in feeding experiments of recombinant COS-1 cells. Substrate specificity of recombinant AKR1C isozymes, overview. The isozymes also have 17beta-hydroxysteroid dehydrogenase activity. No activity with 4-androstenedione and testosterone, and poor activity with 4-hydroxytestosterone (4-OHT)
Products: -
Products: -
?
additional information
?
-
Substrates: identification of metabolites by GC-MSMS in feeding experiments of recombinant COS-1 cells. Substrate specificity of recombinant AKR1C isozymes, overview. The isozymes also have 17beta-hydroxysteroid dehydrogenase activity. No activity with 4-androstenedione, testosterone, and 4-hydroxytestosterone (4-OHT)
Products: -
Products: -
?
additional information
?
-
Substrates: identification of metabolites by GC-MSMS in feeding experiments of recombinant COS-1 cells. Substrate specificity of recombinant AKR1C isozymes, overview. The isozymes also have 17beta-hydroxysteroid dehydrogenase activity. No activity with 4-androstenedione, testosterone, and 4-hydroxytestosterone (4-OHT)
Products: -
Products: -
?
additional information
?
-
Substrates: identification of metabolites by GC-MSMS in feeding experiments of recombinant COS-1 cells. Substrate specificity of recombinant AKR1C isozymes, overview. The isozymes also have 17beta-hydroxysteroid dehydrogenase activity. No activity with 4-androstenedione, testosterone, and 4-hydroxytestosterone (4-OHT)
Products: -
Products: -
?
additional information
?
-
Substrates: identification of metabolites by GC-MSMS in feeding experiments of recombinant COS-1 cells. Substrate specificity of recombinant AKR1C isozymes, overview. The isozymes also have 17beta-hydroxysteroid dehydrogenase activity. No activity with 4-androstenedione, testosterone, and 4-hydroxytestosterone (4-OHT)
Products: -
Products: -
?
additional information
?
-
Substrates: identification of metabolites by GC-MSMS in feeding experiments of recombinant COS-1 cells. Substrate specificity of recombinant AKR1C isozymes, overview. The isozymes also have 17beta-hydroxysteroid dehydrogenase activity. No activity with testosterone and 4-androstenedione
Products: -
Products: -
?
additional information
?
-
Substrates: identification of metabolites by GC-MSMS in feeding experiments of recombinant COS-1 cells. Substrate specificity of recombinant AKR1C isozymes, overview. The isozymes also have 17beta-hydroxysteroid dehydrogenase activity. No activity with testosterone and 4-androstenedione
Products: -
Products: -
?
additional information
?
-
Substrates: identification of metabolites by GC-MSMS in feeding experiments of recombinant COS-1 cells. Substrate specificity of recombinant AKR1C isozymes, overview. The isozymes also have 17beta-hydroxysteroid dehydrogenase activity. No activity with testosterone and 4-androstenedione
Products: -
Products: -
?
additional information
?
-
Substrates: identification of metabolites by GC-MSMS in feeding experiments of recombinant COS-1 cells. Substrate specificity of recombinant AKR1C isozymes, overview. The isozymes also have 17beta-hydroxysteroid dehydrogenase activity. No activity with testosterone and 4-androstenedione
Products: -
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?
additional information
?
-
Substrates: enzyme is strictly NADPH-specific
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?
additional information
?
-
-
Substrates: enzyme is strictly NADPH-specific
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?
additional information
?
-
Substrates: no activity with testosterone, 3-oxo-desogestrel, progesterone, NKI 42255, trans-benzene dihydrodiol and cis-benzene dihydrodiol
Products: -
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?
additional information
?
-
-
Substrates: NADH binding to the recombinant enzyme Ps3alphaHSD and its mutants is thermodynamically analyzed using isothermal titration calorimetry
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
17beta-estradiol + NAD(P)H + H+
estrone + NAD(P)+
Substrates: -
Products: -
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?
20alpha-hydroxyprogesterone + NAD(P)H + H+
progesterone + NAD(P)+
Substrates: -
Products: -
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?
3alpha-androstanediol + NAD(P)+
5alpha-dihydrotestosterone + NAD(P)H + H+
Substrates: -
Products: -
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r
4-hydroxyandrostenedione + NADPH + H+
3alpha,4beta-dihydroxy-5alpha-androstan-17-one + NADP+
Substrates: -
Products: -
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?
5alpha-androstane-3,17-dione + NAD(P)H + H+
androsterone + NAD(P)+
Substrates: -
Products: -
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?
5alpha-androstane-3alpha,17beta-diol + NADP+
(5alpha)-androstan-17-beta-ol-3-one + NADPH + H+
-
Substrates: -
Products: -
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?
5alpha-dihydroprogesterone + NADPH + H+
allopregnanolone + 5alpha,20alpha-tetrahydroprogesterone + NADP+
Substrates: -
Products: -
Products: -
r
5alpha-dihydrotestosterone + NADPH + H+
3alpha-androstanediol + NADP+
Substrates: physiological inactivation of the most potent androgen 5alpha dihydrotestosterone
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r
5alpha-dihydrotestosterone + NADPH + H+
5alpha-androstane-3alpha,17beta-diol + NADP+
Substrates: -
Products: -
Products: -
r
5beta-androstan-3alpha-ol-17-one + NADP+
(5beta)-androstan-3,17-dione + NADPH + H+
-
Substrates: -
Products: -
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?
5beta-androstane-3alpha,17beta-diol + NADP+
5beta-androstan-17beta-ol-3-one + NADPH + H+
-
Substrates: -
Products: -
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?
5beta-dihydroprogesterone + NADPH + H+
pregnanolone + NADP+
Substrates: -
Products: -
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r
7alpha,12alpha-dihydroxy-5beta-cholestan-3-one + NAD(P)+
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestane + NAD(P)H + H+
-
Substrates: -
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?
allopregnanolone + 5alpha,20alpha-tetrahydroprogesterone + NADP+
5alpha-dihydroprogesterone + NADPH + H+
Substrates: -
Products: -
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r
androsterone + NAD(P)+
5alpha-androstane-3,17-dione + NAD(P)H + H+
Substrates: -
Products: -
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?
androsterone + NAD+
(5alpha)-androstane-3,17-dione + NADH + H+
-
Substrates: -
Products: -
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?
androsterone + NAD+
5alpha-androstan-3,17-dione + NADH + H+
Substrates: -
Products: -
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r
androsterone + NAD+
androstanedione + NADH + H+
Substrates: -
Products: -
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r
androsterone + NADP+
(5alpha)-androstane-3,17-dione + NADPH + H+
-
Substrates: -
Products: -
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?
cholic acid + NAD+
dehydrocholic acid + NADH + H+
-
Substrates: -
Products: -
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r
estrone + NAD(P)H + H+
17beta-estradiol + NAD(P)+
Substrates: -
Products: -
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?
progesterone + NAD(P)H + H+
20alpha-hydroxyprogesterone + NAD(P)+
Substrates: -
Products: -
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?
testosterone + NAD(P)H + H+
DELTA4-androstene-3,17-dione + NAD(P)+
Substrates: -
Products: -
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?
5alpha-dihydroprogesterone + NADPH + H+
5alpha,20alpha-tetrahydroprogesterone + NADP+
Substrates: reaction of EC 1.1.1.149
Products: -
Products: -
r
5alpha-dihydroprogesterone + NADPH + H+
5alpha,20alpha-tetrahydroprogesterone + NADP+
Substrates: reaction of EC 1.1.1.149
Products: -
Products: -
r
5alpha-dihydroprogesterone + NADPH + H+
5alpha,20alpha-tetrahydroprogesterone + NADP+
Substrates: reaction of EC 1.1.1.149
Products: -
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r
5alpha-dihydrotestosterone + NAD(P)H + H+
3alpha-androstanediol + NAD(P)+
Substrates: -
Products: -
Products: -
r
5alpha-dihydrotestosterone + NAD(P)H + H+
3alpha-androstanediol + NAD(P)+
-
Substrates: -
Products: -
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?
a 3alpha-hydroxysteroid + NAD(P)+
a 3-oxosteroid + NAD(P)H + H+
Substrates: -
Products: -
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?
a 3alpha-hydroxysteroid + NAD(P)+
a 3-oxosteroid + NAD(P)H + H+
Substrates: -
Products: -
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?
a 3alpha-hydroxysteroid + NAD(P)+
a 3-oxosteroid + NAD(P)H + H+
Substrates: -
Products: -
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r
a 3alpha-hydroxysteroid + NAD(P)+
a 3-oxosteroid + NAD(P)H + H+
Substrates: -
Products: -
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?
a 3alpha-hydroxysteroid + NAD+
a 3-oxosteroid + NADH + H+
Substrates: -
Products: -
Products: -
r
a 3alpha-hydroxysteroid + NAD+
a 3-oxosteroid + NADH + H+
Substrates: -
Products: -
Products: -
r
a 3alpha-hydroxysteroid + NAD+
a 3-oxosteroid + NADH + H+
Substrates: -
Products: -
Products: -
r
dihydroprogesterone + NADPH + H+
allopregnanolone + NADP+
Substrates: -
Products: -
Products: -
?
dihydroprogesterone + NADPH + H+
allopregnanolone + NADP+
-
Substrates: -
Products: -
Products: -
?
dihydrotestosterone + NADPH + H+
4-androsten-3alpha,17beta-diol + NADP+
Substrates: low activity
Products: -
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?
dihydrotestosterone + NADPH + H+
4-androsten-3alpha,17beta-diol + NADP+
Substrates: high activity
Products: -
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?
dihydrotestosterone + NADPH + H+
4-androsten-3alpha,17beta-diol + NADP+
Substrates: -
Products: -
Products: -
r
dihydrotestosterone + NADPH + H+
4-androsten-3alpha,17beta-diol + NADP+
Substrates: -
Products: -
Products: -
r
dihydrotestosterone + NADPH + H+
4-androsten-3alpha,17beta-diol + NADP+
Substrates: -
Products: -
Products: -
r
dihydrotestosterone + NADPH + H+
5alpha-androstane-3alpha,17beta-diol + NADP+
Substrates: -
Products: -
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?
dihydrotestosterone + NADPH + H+
5alpha-androstane-3alpha,17beta-diol + NADP+
-
Substrates: -
Products: -
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?
additional information
?
-
Substrates: the enzyme catalyzes reversibly the oxidoreduction of 3alpha-hydroxyl groups of steroid hormones
Products: -
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?
additional information
?
-
Substrates: the enzyme catalyzes reversibly the oxidoreduction of 3alpha-hydroxyl groups of steroid hormones
Products: -
Products: -
?
additional information
?
-
-
Substrates: isoform AKR1C2 functions preferentially as a 3-ketosteroid reductase
Products: -
Products: -
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NADPH
usage of NADPH-Na4 to NADP-Na2 in enzyme activity assays
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
no effect by 0.5 mM of Mg2+, Ni2+, and Al3+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(3,6-dihydropyridin-1(2H)-yl)(1H-indol-2-yl)methanone
crystal structure analysis of enzyme-inhibitor complex
(5-methyl-1H-indol-2-yl)(4-propylpiperidin-1-yl)methanone
crystal structure analysis of enzyme-inhibitor complex
2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane
-
hydroxychlor (HPTE), competitive without cofactor but mixed-type inhibition with cofactor, methoxychlor and its metabolite HPTE inhibit rat neurosteroidogenic 3alpha-hydroxysteroid dehydrogenase
3-pentyl-2-[[(pyridin-2-yl)methyl]sulfanyl]-7-(pyrrolidine-1-carbonyl)quinazolin-4(3H)-one
crystal structure analysis of enzyme-inhibitor complex
4-chloro-N-[(4-chlorophenyl)methyl]-5-nitro-1H-pyrazole-3-carboxamide
crystal structure analysis of enzyme-inhibitor complex
4-nitro-2-([4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]methyl)phenol
crystal structure analysis of enzyme-inhibitor complex
5-(benzenesulfonyl)-2-nitrophenol
crystal structure analysis of enzyme-inhibitor complex
apigenin
about 90% inhibition at 0.1 mM, inhibition kinetics. Apigenin inhibits AKR1C9 in a mixed-type inhibitory mode when the cofactor is used. This indicates that apigenin also affects the cofactor-binding site besides its binding to the active site of the steroid substrate. Docking analysis of the binding of apigenin to rat AKR1C9 with bound NADPH and substrate dihydrotestsosterone
methoxychlor
-
MXC, methoxychlor and its metabolite hydroxychlor (HPTE) inhibit rat neurosteroidogenic 3alpha-hydroxysteroid dehydrogenase. Methoxychlor is primarily used as an insecticide, and it is widely present in the environment
ursodeoxycholate
micromolar inhibitor, competitive inhibitor versus 5alpha-dihydroprogesterone and uncompetitive inhibitor versus NADPH
additional information
crystal structures of complexes of 17beta-HSD5 with structurally diverse inhibitors derived from high-throughput inhibitor screening, overview. Analysis of interactions between 17beta-HSD5 and inhibitors at the atomic level which enable structure-based drug design for anti-CRPC therapy
-
additional information
flufenamic acid inhibits the isozyme's 17beta-oxosteroid reductase activity
-
additional information
flufenamic acid inhibits the isozyme's 17beta-oxosteroid reductase activity
-
additional information
flufenamic acid inhibits the isozyme's 17beta-oxosteroid reductase activity
-
additional information
flufenamic acid inhibits the isozyme's 17beta-oxosteroid reductase activity
-
additional information
-
binding mode determination of methoxychlor (MXC) and HPTE from the crystal structure of AKR1C14 by molecular docking. HPTE has a higher affinity with the enzyme than methoxychlor. HPTE is more potent than methoxychlor to inhibit both AKR1C14 and retinol dehydrogenase 2 (RDH2, EC 1.1.1.53). Both MXC and HPTE interact with Y55, K84, H117, W227, and Y310 of the enzyme. HPTE also forms hydrogen bond with V25 residue of AKR1C14. Both MXC and HPTE inhibit rat AKR1C14 in a competitive mode against DHT. No inhibition by DMSO
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Adenocarcinoma
A novel variant of ileal bile acid binding protein is up-regulated through nuclear factor-kappaB activation in colorectal adenocarcinoma.
Adenocarcinoma
Aldo-keto reductase family 1 member C3 (AKR1C3) is expressed in adenocarcinoma and squamous cell carcinoma but not small cell carcinoma.
Adenocarcinoma
Expression of aldo-keto reductase family 1 member C3 (AKR1C3) in neuroendocrine tumors & adenocarcinomas of pancreas, gastrointestinal tract, and lung.
Alzheimer Disease
Increased ileal bile acid binding protein and galectin-9 are associated with mild cognitive impairment and Alzheimer's disease.
Carcinoma
Aldo-keto reductase family 1 member C3 (AKR1C3) is expressed in adenocarcinoma and squamous cell carcinoma but not small cell carcinoma.
Carcinoma, Small Cell
Aldo-keto reductase family 1 member C3 (AKR1C3) is expressed in adenocarcinoma and squamous cell carcinoma but not small cell carcinoma.
Carcinoma, Squamous Cell
Aldo-keto reductase family 1 member C3 (AKR1C3) is expressed in adenocarcinoma and squamous cell carcinoma but not small cell carcinoma.
Choriocarcinoma
AKR1C3 overexpression mediates methotrexate resistance in choriocarcinoma cells.
Colitis, Ulcerative
Microproteomics and Immunohistochemistry Reveal Differences in Aldo-Keto Reductase Family 1 Member C3 in Tissue Specimens of Ulcerative Colitis and Crohn's Disease.
Colonic Neoplasms
The bile acid nuclear receptor FXR and the bile acid binding protein IBABP are differently expressed in colon cancer.
Crohn Disease
Microproteomics and Immunohistochemistry Reveal Differences in Aldo-Keto Reductase Family 1 Member C3 in Tissue Specimens of Ulcerative Colitis and Crohn's Disease.
Fatty Liver
Effects of sanshoamides and capsaicinoids on plasma and liver lipid metabolism in hyperlipidemic rats.
Hyperandrogenism
DNA methylome profiling of granulosa cells reveals altered methylation in genes regulating vital ovarian functions in polycystic ovary syndrome.
Hypercholesterolemia
The role of the enterohepatic circulation of bile salts and nuclear hormone receptors in the regulation of cholesterol homeostasis: Bile salts as ligands for nuclear hormone receptors.
Neoplasms
Bruton's Tyrosine Kinase Inhibitors Ibrutinib and Acalabrutinib Counteract Anthracycline Resistance in Cancer Cells Expressing AKR1C3.
Neoplasms
Clinical implications of aldo-keto reductase family 1 member C3 and its relationship with lipocalin 2 in cancer of the uterine cervix.
Neoplasms
DNA methylome profiling of granulosa cells reveals altered methylation in genes regulating vital ovarian functions in polycystic ovary syndrome.
Neoplasms
Expression of androgen receptor through androgen-converting enzymes is associated with biological aggressiveness in prostate cancer.
Neuroendocrine Tumors
Expression of aldo-keto reductase family 1 member C3 (AKR1C3) in neuroendocrine tumors & adenocarcinomas of pancreas, gastrointestinal tract, and lung.
Prostatic Neoplasms
AKR1C3 expression in primary lesion rebiopsy at the time of metastatic castration-resistant prostate cancer is strongly associated with poor efficacy of abiraterone as a first-line therapy.
Prostatic Neoplasms
AKR1C3 overexpression may serve as a promising biomarker for prostate cancer progression.
Prostatic Neoplasms
Aldo-keto reductase family 1 member C3 (AKR1C3) is a biomarker and therapeutic target for castration-resistant prostate cancer.
Prostatic Neoplasms
Berberine inhibits androgen synthesis by interaction with aldo-keto reductase 1C3 in 22Rv1 prostate cancer cells.
Prostatic Neoplasms
Consecutive Prostate Cancer Specimens Revealed Increased Aldo?Keto Reductase Family 1 Member C3 Expression with Progression to Castration-Resistant Prostate Cancer.
Prostatic Neoplasms
Quality of life effects of androgen deprivation therapy in a prostate cancer cohort in New Zealand: can we minimize effects using a stratification based on the aldo-keto reductase family 1, member C3 rs12529 gene polymorphism?
Urinary Bladder Neoplasms
Cisplatin resistance by induction of aldo-keto reductase family 1 member C2 in human bladder cancer cells.
Uterine Cervical Neoplasms
Clinical implications of aldo-keto reductase family 1 member C3 and its relationship with lipocalin 2 in cancer of the uterine cervix.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1
2-(1-imidazolyl)-1-(4-methoxyphenyl)-2-methyl-1-propanone
pH 7.0, temperature not specified in the publication, NAD(P)H
0.035
3-dehydro-beta-ecdysone
pH 7.0, temperature not specified in the publication, NAD(P)H
0.0018
5alpha-dihydroprogesterone
in 100 mM potassium phosphate, pH 7.0, at 25°C
0.0328
androstandiol
pH 8.9, temperature not specified in the publication, NAD(P)+
0.0357
androstandione
pH 7.0, temperature not specified in the publication, NAD(P)H
0.0207
epiandrosterone
pH 8.9, temperature not specified in the publication, NAD(P)+
2.1
metyrapol
pH 8.9, temperature not specified in the publication, NAD(P)+
0.16
(R)-tetralol
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.38
(R)-tetralol
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.68
(R)-tetralol
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.146
(S)-indan-1-ol
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.28
(S)-indan-1-ol
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.42
(S)-indan-1-ol
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.11
(S)-tetralol
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.24
(S)-tetralol
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.29
(S)-tetralol
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.025
3-dehydro-alpha-ecdysone
pH 7.0, temperature not specified in the publication, NAD(P)H
0.028
3-dehydro-alpha-ecdysone
pH 7.0, temperature not specified in the publication, NAD(P)H
0.0152
3alpha-hydroxydesogestrel
pH 8.9, temperature not specified in the publication, NAD(P)+
0.0216
3alpha-hydroxydesogestrel
pH 8.9, temperature not specified in the publication, NAD(P)+
0.9
4-Nitroacetophenone
pH 7.0, temperature not specified in the publication, NAD(P)H
1
4-Nitroacetophenone
pH 7.0, temperature not specified in the publication, NAD(P)H
1
4-nitrobenzaldehyde
pH 7.0, temperature not specified in the publication, NAD(P)H
1.09
4-nitrobenzaldehyde
pH 7.0, temperature not specified in the publication, NAD(P)H
0.0001
5alpha-androstan-17-beta-ol-3-one
mutant F217S, pH 7.4, 25°C
0.0022
5alpha-Androstan-3alpha-ol-17-one
-
recombinant enzyme, at pH 7.4 and 25°C
0.0008
5alpha-androstane-3alpha,17beta-diol
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.0026
5alpha-androstane-3alpha,17beta-diol
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.0031
5alpha-androstane-3alpha,17beta-diol
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.00218
5alpha-dihydrotestosterone
pH 7.4, 37°C, recombinant wild-type enzyme
0.0161
5alpha-dihydrotestosterone
pH 7.0, temperature not specified in the publication, NAD(P)H
0.019
5alpha-dihydrotestosterone
pH 7.0, temperature not specified in the publication, NAD(P)H
0.0002
5alpha-pregnan-20alpha-ol-3-one
mutant F217S, pH 7.4, 25°C
0.0006
5beta-Androstan-3alpha-ol-17-one
mutant F217S, pH 7.4, 25°C
0.0009
5beta-Androstan-3alpha-ol-17-one
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.0014
5beta-Androstan-3alpha-ol-17-one
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.0018
5beta-Androstan-3alpha-ol-17-one
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.0012
5beta-androstane-3alpha,17beta-diol
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.0021
5beta-androstane-3alpha,17beta-diol
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.0022
5beta-androstane-3alpha,17beta-diol
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.0111
5beta-dihydrotestosterone
pH 7.0, temperature not specified in the publication, NAD(P)H
0.0201
5beta-dihydrotestosterone
pH 7.0, temperature not specified in the publication, NAD(P)H
0.001
5beta-pregnane-3alpha,20alpha-diol
-
recombinant enzyme, at pH 7.4 and 25°C
0.0005
androsterone
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.0022
androsterone
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.0027
androsterone
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.0028
androsterone
reombinant His-tagged enzyme, pH 10.5, 25°C
0.0244
androsterone
pH 8.9, temperature not specified in the publication, NAD(P)+
0.0267
androsterone
pH 8.9, temperature not specified in the publication, NAD(P)+
0.0011
chenodeoxycholic acid
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.0023
chenodeoxycholic acid
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.0029
chenodeoxycholic acid
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.025
cholic acid
pH 8.9, temperature not specified in the publication, NAD(P)+
0.0301
cholic acid
pH 8.9, temperature not specified in the publication, NAD(P)+
0.032
cholic acid
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.041
cholic acid
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.059
cholic acid
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
56
cholic acid
-
recombinant His-tagged wild-type enzyme, pH 8.0, 37°C
78
cholic acid
-
recombinant His-tagged mutant S114A/Y153F, pH 8.0, 37°C
51
Dehydrocholic acid
-
recombinant His-tagged wild-type enzyme, pH 8.0, 37°C
239
Dehydrocholic acid
-
recombinant His-tagged mutant S114A, pH 8.0, 37°C
2489
Dehydrocholic acid
-
recombinant His-tagged mutant Y153F, pH 8.0, 37°C
0.0013
deoxycholic acid
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.0014
deoxycholic acid
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.0097
deoxycholic acid
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.003
Fusidic acid
pH 8.9, temperature not specified in the publication, NAD(P)+
0.0061
Fusidic acid
pH 8.9, temperature not specified in the publication
0.0068
Fusidic acid
pH 8.9, temperature not specified in the publication, NAD(P)+
0.001
lithocholic acid
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.0018
lithocholic acid
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.0019
lithocholic acid
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.61
Metyrapone
pH 7.0, temperature not specified in the publication, NAD(P)H
0.63
Metyrapone
pH 7.0, temperature not specified in the publication, NAD(P)H
0.14
NAD+
reombinant His-tagged enzyme, pH 10.5, 25°C, with androstenol
0.39
NAD+
reombinant His-tagged enzyme, pH 10.5, 25°C, with androsterone
0.0005
NADP+
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.0006
NADP+
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
additional information
additional information
Km-value for the 17beta-oxidation of testosterone is 0.00067 mM, and Km-value for the 17beta-reduction of androstenedione is 0.00138 mM
-
additional information
additional information
steady-state kinetics of 3alpha-HSD/CR catalyzed reaction of NADþ with androsterone and the truncated analogues, overview. The uniform binding energy from the B-ring of steroids with the active site of 3alpha-HSD/CR equally contributes 2.1 kcal/mol to stabilize both the transition state and ground state of the ternary complex, leading to the similarity in kcat for 2-decalol and cyclohexanol. Differential binding interactions of the remote BCD-ring and CD-ring of androsterone with the active site of 3alpha-HSD/CR contribute 8.5 and 6.4 kcal/mol to the stabilization of the transition state, respectively. The removal of the carbonyl group at C17 of androsterone has small effects on catalysis. Both uniform and differential binding energies from the remote sites of androsterone compared to cyclohexanol contribute to the 3a-HSD/CR catalysis, resulting in the increases in kcat and kcat/KB
-
additional information
additional information
steady-state kinetics, and stopped-flow study, kinetics of enzyme mutants P185A, P185G, T188A, and T188S showing an increase in kcat, Ka drosterone and KiNAD and equal primary isotope effects of DV and D(V/K)
-
additional information
additional information
steady-state kinetics
-
additional information
additional information
-
steady-state kinetics
-
additional information
additional information
AKR1C isozymes kinetics analysis, steady-state Michaelis-Menten kinetics
-
additional information
additional information
AKR1C isozymes kinetics analysis, steady-state Michaelis-Menten kinetics
-
additional information
additional information
AKR1C isozymes kinetics analysis, steady-state Michaelis-Menten kinetics
-
additional information
additional information
AKR1C isozymes kinetics analysis, steady-state Michaelis-Menten kinetics
-
additional information
additional information
steady-state kinetics and thermodynamics. The effects of temperature on kcat/Km for 3alpha-HSD/CR acting on androsterone, 2-decalol, and cyclohexanol show the reactions are entropically favorable but enthalpically unfavorable. Thermodynamic analysis from the temperature-dependent values of Km and kcat shows the binding of the E-NAD+ complex with either 2-decalol or cyclohexanol to form the ternary complex is endothermic and entropy-driven, and the subsequent conversion to the transition state is both enthalpically and entropically unfavorable
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.003
5alpha-dihydroprogesterone
in 100 mM potassium phosphate, pH 7.0, at 25°C
additional information
additional information
Kcat-value for the 17beta-oxidation of testosterone is 0.000118 1/sec, and Kcat-value for the 17beta-reduction of androstenedione is 0.00112 1/sec
-
0.18
(R)-tetralol
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.38
(R)-tetralol
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.77
(R)-tetralol
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.1
(S)-indan-1-ol
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.27
(S)-indan-1-ol
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.4
(S)-indan-1-ol
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.2
(S)-tetralol
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.27
(S)-tetralol
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.43
(S)-tetralol
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.004
5alpha-androstan-17-beta-ol-3-one
mutant F217S, pH 7.4, 25°C
0.007
5alpha-Androstan-3alpha-ol-17-one
-
recombinant enzyme, at pH 7.4 and 25°C
0.087
5alpha-androstane-3alpha,17beta-diol
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.135
5alpha-androstane-3alpha,17beta-diol
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.35
5alpha-androstane-3alpha,17beta-diol
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.0612
5alpha-dihydrotestosterone
pH 7.4, 37°C, recombinant wild-type enzyme
0.0025
5alpha-pregnan-20alpha-ol-3-one
mutant F217S, pH 7.4, 25°C
0.004
5beta-Androstan-3alpha-ol-17-one
mutant F217S, pH 7.4, 25°C
0.048
5beta-Androstan-3alpha-ol-17-one
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.097
5beta-Androstan-3alpha-ol-17-one
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.18
5beta-Androstan-3alpha-ol-17-one
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.047
5beta-androstane-3alpha,17beta-diol
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.18
5beta-androstane-3alpha,17beta-diol
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.3
5beta-androstane-3alpha,17beta-diol
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.002
5beta-pregnane-3alpha,20alpha-diol
-
recombinant enzyme, at pH 7.4 and 25°C
0.043
androsterone
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.15
androsterone
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.28
androsterone
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.032
chenodeoxycholic acid
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.105
chenodeoxycholic acid
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.13
chenodeoxycholic acid
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.012
cholic acid
-
recombinant His-tagged mutant S114A/Y153F, pH 8.0, 37°C
0.03
cholic acid
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.05
cholic acid
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.2
cholic acid
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
23
cholic acid
-
recombinant His-tagged wild-type enzyme, pH 8.0, 37°C
0.89
Dehydrocholic acid
-
recombinant His-tagged mutant S114A, pH 8.0, 37°C
1.1
Dehydrocholic acid
-
recombinant His-tagged mutant Y153F, pH 8.0, 37°C
48
Dehydrocholic acid
-
recombinant His-tagged wild-type enzyme, pH 8.0, 37°C
0.012
deoxycholic acid
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.018
deoxycholic acid
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.085
deoxycholic acid
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.032
lithocholic acid
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.04
lithocholic acid
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.043
lithocholic acid
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
Kcat/Km-value for the 17beta-oxidation of testosterone is 0.183 1/sec*mM, and Kcat/Km-value for the 17beta-reduction of androstenedione is 0.817 1/sec*mM
-
1
(R)-tetralol
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
1.17
(R)-tetralol
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
1.2
(R)-tetralol
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.68
(S)-indan-1-ol
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
1
(S)-indan-1-ol
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
1
(S)-indan-1-ol
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
1.2
(S)-tetralol
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
1.5
(S)-tetralol
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
1.83
(S)-tetralol
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
10.3
5alpha-androstane-3alpha,17beta-diol
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
96.7
5alpha-androstane-3alpha,17beta-diol
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
135
5alpha-androstane-3alpha,17beta-diol
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
28.07
5alpha-dihydrotestosterone
pH 7.4, 37°C, recombinant wild-type enzyme
53.3
5beta-Androstan-3alpha-ol-17-one
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
96.7
5beta-Androstan-3alpha-ol-17-one
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
101.7
5beta-Androstan-3alpha-ol-17-one
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
70
androsterone
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
86.7
androsterone
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
105
androsterone
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
178571
androsterone
reombinant His-tagged enzyme, pH 10.5, 25°C
28.3
chenodeoxycholic acid
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
45
chenodeoxycholic acid
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
46.7
chenodeoxycholic acid
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.00015
cholic acid
-
recombinant His-tagged mutant S114A/Y153F, pH 8.0, 37°C
0.0005
cholic acid
-
recombinant His-tagged mutant K157A, pH 8.0, 37°C
0.0013
cholic acid
-
recombinant His-tagged mutant Y153F, pH 8.0, 37°C
0.0014
cholic acid
-
recombinant His-tagged mutant S114A, pH 8.0, 37°C
0.411
cholic acid
-
recombinant His-tagged wild-type enzyme, pH 8.0, 37°C
1
cholic acid
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
1.2
cholic acid
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
3.3
cholic acid
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
0.00044
Dehydrocholic acid
-
recombinant His-tagged mutant Y153F, pH 8.0, 37°C
0.0037
Dehydrocholic acid
-
recombinant His-tagged mutant S114A, pH 8.0, 37°C
0.94
Dehydrocholic acid
-
recombinant His-tagged wild-type enzyme, pH 8.0, 37°C
8.8
deoxycholic acid
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
9
deoxycholic acid
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
14.2
deoxycholic acid
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
21.7
lithocholic acid
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
23.3
lithocholic acid
-
mutant enzyme H216Y, in 0.1 M potassium phosphate, pH 7.4, at 25°C
31.7
lithocholic acid
-
wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
266.7
NADP+
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0028
(3,6-dihydropyridin-1(2H)-yl)(1H-indol-2-yl)methanone
Homo sapiens
pH 6.0, 22°C
0.000037
(5-methyl-1H-indol-2-yl)(4-propylpiperidin-1-yl)methanone
Homo sapiens
pH 6.0, 22°C
0.0026
2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane
Rattus norvegicus
-
pH 7.2, 37°C, recombinant enzyme
0.0029
3-pentyl-2-[[(pyridin-2-yl)methyl]sulfanyl]-7-(pyrrolidine-1-carbonyl)quinazolin-4(3H)-one
Homo sapiens
pH 6.0, 22°C
0.0026
4-chloro-N-[(4-chlorophenyl)methyl]-5-nitro-1H-pyrazole-3-carboxamide
Homo sapiens
pH 6.0, 22°C
0.00049
4-nitro-2-([4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]methyl)phenol
Homo sapiens
pH 6.0, 22°C
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
15.4
recombinant untagged enzyme purified via deoxycholic acid affinity chromatography, pH 11.0, 25°C
3.94
recombinant His-tagged enzyme purified via Ni2+ affinity chromatography, pH 11.0, 25°C
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.2
7.4
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
15 - 45
optimum at 30°C, over 60% of maximal activity in the range of 25-45°C, with the temperature increasing from 30°C to 45°C, the enzyme activity gradually decreases to 77.55% of the optimum whereas with the temperature decreasing from 30°C to 15°C, the enzyme activity rapidly drops to 39.4% of the optimum
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
parallel expression of Siah2 and AKR1C3 in human prostate cancer tissues
brenda
additional information
in addition to neurons, 3alpha-HSOR activity appears to be highly localized in glial cells, such as type 1 astrocytes in culture and oligodendrocytes, although, 3alpa-HSOR activity has not been detected in myelin membranes of the CNS
brenda
analysis of 3alpha-HSOR mRNA distribution in the mouse brain by in situ hybridization has shown that this enzyme is co-localized with 5alpha-R type 1 in neurons of the cerebral cortex, hippocampus, olfactory bulb, amygdala and thalamus. And 3alpha-HSOR immunoreactivity is largely distributed in both white and gray matters
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Highest Expressing Human Cell Lines
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
the enzyme belongs to the AKR1C subfamily, the members of which catalyze the reduction of ketosteroids and ketoprostaglandins
evolution
enzyme 3alpha-HSD/CR belongs to the short chain dehydrogenase/ reductase (SDR) superfamily
evolution
human 3alpha-HSD3 shares 97.8% sequence identity with human 20-alpha hydroxysteroid dehydrogenase (20alpha-HSD) and there is only one amino acid difference (residue 54) that is located in their steroid binding pockets. 20alpha-HSD displays a distinctive ability in transforming progesterone to 20alpha-hydroxy-progesterone
evolution
3alpha-HSOR is a member of the aldo-keto reductase superfamily
malfunction
downregulation of 3alpha-HSD3 decreases MCF-7 breast cancer cell growth
malfunction
mutation at P185 in the hinge region and T188 in the loop causes a significant increase in the Kd value for NADH. Mutants P185A, P185G, T188A, and T188S show an increase the dissociation of the nucleotide cofactor, thereby increasing the rate of release of the product and producing the rate-limiting step in the hydride transfer
malfunction
the V54L mutation significantly decreases the 3alpha-HSD activity for the reduction of 5alpha-dihydrotestosterone, while this mutation enhances the 20alpha-HSD activity to convert progesterone
malfunction
the expression of 5alpha-reductase (5alpha-R) and 3alpha-hydroxysteroid oxidoreductase (3alpha-HSOR) and the levels of progesterone (PROG) and testosterone (T) reduced metabolites show regional and sex differences in the nervous system and are affected by changing physiological conditions as well as by neurodegenerative and psychiatric disorders. A decrease in their nervous tissue levels may negatively impact the course and outcome of some pathological events. In other pathological conditions their increased levels may have a negative impact. Thus, the use of synthetic analogues of these steroids or 5alpha-R modulation have been proposed as therapeutic approaches for several nervous system pathologies. Changes in brain levels of PROG metabolites have been detected in Alzheimer's disease (AD) mouse models, such as the 3xTg-AD mouse
malfunction
-
loss of hydrogen bonding with NADH upon the Y153F mutation results in increased enthalpy change, partially compensated by increased entropy change. The NADH binding affinity of K157A mutant is much lower than that of the wild-type, mainly due to loss of a hydrogen bond. The decreased affinity results in decreased kcat. Compared to the wild-type, the mutants S114A and Y153F show higher Km and lower kcat values in both oxidation and reduction reactions. Simultaneous mutation of S114A and Y153F results in a significant decrease in kcat relative to the single mutant
malfunction
the expression of 5alpha-reductase (5alpha-R) and 3alpha-hydroxysteroid oxidoreductase (3alpha-HSOR) and the levels of progesterone (PROG) and testosterone (T) reduced metabolites show regional and sex differences in the nervous system and are affected by changing physiological conditions as well as by neurodegenerative and psychiatric disorders. A decrease in their nervous tissue levels may negatively impact the course and outcome of some pathological events. In other pathological conditions their increased levels may have a negative impact. Thus, the use of synthetic analogues of these steroids or 5alpha-R modulation have been proposed as therapeutic approaches for several nervous system pathologies. Low plasma testosterone levels are significantly associated with increased risk of Alzheimer's disease in elderly men, while higher free testosterone levels in women are associated with lower cerebral Abeta positivity
metabolism
enzyme is involved in inactivation of steroid hormones
metabolism
-
3alpha-hydroxysteroid dehydrogenase isoform AKR1C4 plays a significant role in bile acid biosynthesis, steroid hormone metabolism, and xenobiotic metabolism
metabolism
the enzymatic complex 5alpha-reductase (5alpha-R) and 3alpha/3beta-hydroxysteroid oxidoreductase (HSOR) is expressed in the nervous system, where it transforms progesterone (PROG) and testosterone (T) into neuroactive metabolites. These metabolites regulate myelination, brain maturation, neurotransmission, reproductive behavior and the stress response. The expression of 5alpha-R and 3alpha-HSOR and the levels of PROG and T reduced metabolites show regional and sex differences in the nervous system and are affected by changing physiological conditions as well as by neurodegenerative and psychiatric disorders. Biosynthesis of progesterone and testosterone metabolites and their mechanism of action, overview
metabolism
the enzymatic complex 5alpha-reductase (5alpha-R) and 3alpha/3beta-hydroxysteroid oxidoreductase (HSOR) is expressed in the nervous system, where it transforms progesterone (PROG) and testosterone (T) into neuroactive metabolites. These metabolites regulate myelination, brain maturation, neurotransmission, reproductive behavior and the stress response. The expression of 5alpha-R and 3alpha-HSOR and the levels of PROG and T reduced metabolites show regional and sex differences in the nervous system and are affected by changing physiological conditions as well as by neurodegenerative and psychiatric disorders. Biosynthesis of progesterone and testosterone metabolites and their mechanism of action, overview
metabolism
human aldo-keto reductases (AKR1C1-AKR1C4, AKR1Cs) play an important role in the intracellular metabolism of steroids. All AKR1Cs have both 3alpha- and 3beta-HSD activities, AKR1C2 and AKR1C4 have a higher 3alpha-HSD activity, whereas AKR1C1 and AKR1C3 have a higher 3beta-HSD activity
metabolism
the synthesis of allopregnanolone (ALLO) and 5alpha-androstane-3alpha,17beta-diol (DIOL) needs 5alpha-reductase 1 (SRD5A1) and 3alpha-hydroxysteroid dehydrogenase (AKR1C9). SRD5A1 is a microsomal NADPH-dependent enzyme, which metabolizes progesterone into dihydroprogesterone or testosterone into dihydrotestosterone (DHT). Subsequently, cytosolic NADPH-dependent AKR1C9 metabolizes the above steroid intermediates into ALLO and DIOL, respectively. Another microsomal NAD+-dependent retinol dehydrogenase 2 (RoDH2, EC 1.1.1.53) catalyzes the opposite direction of AKR1C9. Thus, the levels of ALLO and DIOL also depend on the activity of RoDH2. These three enzymes have been shown to be present in the brain
metabolism
-
the homeostasis of neurosteroids, such as allopregnanolone and 5alpha-androstane-3alpha,17beta-diol (DIOL), depends on the catalysis of AKR1C14 and RDH2. These two enzymes are present in the different subcellular regions, with AKR1C14 in the cytoplasm and RDH2 in the smooth endoplasmic reticulum (microsome), and they use different cofactors, with AKR1C14 of NADPH and RDH2 of NAD+, and the cofactor availability determines the catalytic direction
metabolism
the enzymatic complex 5alpha-reductase (5alpha-R) and 3alpha/3beta-hydroxysteroid oxidoreductase (HSOR) is expressed in the nervous system, where it transforms progesterone (PROG) and testosterone (T) into neuroactive metabolites. These metabolites regulate myelination, brain maturation, neurotransmission, reproductive behavior and the stress response. The expression of 5alpha-R and 3alpha-HSOR and the levels of PROG and T reduced metabolites show regional and sex differences in the nervous system and are affected by changing physiological conditions as well as by neurodegenerative and psychiatric disorders. Biosynthesis of progesterone and testosterone metabolites and their mechanism of action, overview
metabolism
-
enzyme is involved in inactivation of steroid hormones
-
physiological function
the steroidogenic enzyme AKR1C3 regulates stability of the ubiquitin ligase Siah2 in prostate cancer cells. AKR1C3 binds and stabilizes Siah2 by blocking Siah2 self-ubiquitination and degradation. It has a catalytic independent role on androgen receptor activity via Siah2 that promotes activity of androgen receptor in prostate cancer cells. AKR1C3 is a downstream effector of Siah2 in Rv1 cells
physiological function
3alpha-hydroxysteroid dehydrogenase type 3 plays an essential role in the inactivation of the most potent androgen 5alpha-dihydrotestosterone
physiological function
3alpha-hydroxysteroid dehydrogenase catalyzes the oxidation of the 3-hydroxyl group of steroids. The enzymatic conversion is a critical step in the enzymatic assay of urinary sulfated bile acids
physiological function
3-alpha hydroxysteroid dehydrogenase type 3 has an essential role in the inactivation of 5alpha-dihydrotestosterone preventing binding and activation of androgen receptor from overflowing androgen
physiological function
the enzymatic complex 5alpha-R and 3alpha-HSOR colocalizes in glutamatergic and GABAergic neurons of the cerebral cortex, hippocampus, amygdala and thalamus, suggesting that metabolites so formed are relevant for neurotransmitter synthesis and the modulation of their activity in these cells. The metabolites of progesterone (PROG) and testosterone (T) formed by the action of the enzymatic complex 5alpha-R and 3alpha- or 3beta-HSOR have a profound physiological impact in the nervous system, because they are also ligands for a variety of neuronal and glial receptors that are not directly modulated by PROG and T. The reduced metabolites of PROG are also involved in mood regulation. Actions of progesterone and testosterone metabolites in physiological conditions, overview. The enzyme is involed in regulation of the levels of progesterone and testosterone reduced metabolites in the nervous system
physiological function
the enzymatic complex 5alpha-R and 3alpha-HSOR colocalizes in glutamatergic and GABAergic neurons of the cerebral cortex, hippocampus, amygdala and thalamus, suggesting that metabolites so formed are relevant for neurotransmitter synthesis and the modulation of their activity in these cells. The metabolites of progesterone (PROG) and testosterone (T) formed by the action of the enzymatic complex 5alpha-R and 3alpha- or 3beta-HSOR have a profound physiological impact in the nervous system, because they are also ligands for a variety of neuronal and glial receptors that are not directly modulated by PROG and T. The reduced metabolites of PROG are also involved in mood regulation. Actions of progesterone and testosterone metabolites in physiological conditions, overview. The enzyme is involed in regulation of the levels of progesterone and testosterone reduced metabolites in the nervous system. Tetrahydroprogesterone (THP) treatment reduces seizures, prevents cell apoptosis in the spinal cord of STZ diabetic and protects against stroke, oxygen-glucose deprivation
physiological function
the enzyme metabolizes the aromatase inhibitor formestane (4-hydroxandrostenedione, 4-OHA), which binds with high affinity to the androgen receptor, molecular docking and binding kinetics. All recombinant AKR1C isozymes reduce 4-androstenedione to testosterone presenting 17-oxo reductase activity. AKR1C3 is most active as a 17-oxosteroid reductase followed by AKR1C1 and then AKR1C2, whereas AKR1C4 only weakly reduces 4-androstenedione to testosterone. For dihydrotestosterone (DHT), all four enzymes exhibit both 3alpha/beta-oxoreductase activities to various degrees. The major sources of 3beta-diol are AKR1C1, AKR1C3, and AKR1C4, and that of 3alpha-diol is AKR1C2. In this set-up, isolated AKR1C4 preferentially catalysed the 3beta-reduction of DHT. Inhibition by phenolphthalein changes the stereoselectivity back to the normal 3alpha-reduction. For testosterone, the AKR1C isozymes have no catalytic function and even no oxidative 17beta-HSD activity. For 4-hydroxyandrostenedione (4-OHA), some AKR1Cs behave as 17beta-HSD or as 3beta-HSD, but all AKR1Cs convert 4-OHA to 3alpha,4beta-dihydroxy-5alpha-androstan-17-one, possibly reducing the oxo-group at C4, thereby eliminating the double bond to varying extent. AKR1C3 is most active as a 17-oxosteroid reductase. AKR1C4 shows higher activities of 4-oxo-reductase, 3alpha-HSD, and 3beta-HSD, producing the largest amount of 3alpha,4beta-dihydroxy-5alpha-androstan-17-one and 3beta,4beta-dihydroxy-5alpha-androstan-17-one. Like testosterone, 4-hydroxytestosterone (4-OHT) is not a good substrate for isozymes AKR1C1 and AKR1C2. In contrast to testosterone, 4-OHT undergoes some AKR1C catalysed metabolism. Both AKR1C3 and AKR1C4 have some oxidative 17beta-HSD activity, and AKR1C4 has additional obvious 4-5 double bond reductase and 3-oxoreductase activities, making a good production of to 3alpha,4beta-dihydroxy-5alpha-androstan-17-one. AKR1C3 predominantly catalyzes the reduction at C17 of 4-andostenedione as a first step, whereas it catalyzes the first step in the metabolism of 4-OHT as oxidative 17beta-HSD. Apparently, AKR1C4 also catalyses the way of 4-OHT via a special 17beta-hydroxy pathway to 3alpha-adiol, a pathway whereby the 17beta-OH-group is preserved
physiological function
the cytosolic NADPH-dependent AKR1C9 metabolizes the steroid intermediates dihydroprogesterone and dihydrotestosterone into allopregnanolone (ALLO) and 5alpha-androstane-3alpha,17beta-diol (DIOL), respectively
physiological function
-
enzyme AKR1C14 adds a hydrogen to the 3alpha-position of many steroids, including neurosteroids. It is a cytosolic NADPH-dependent enzyme, which primarily catalyzes the formation of allopregnanolone or 5alpha-androstane-3alpha,17beta-diol (DIOL) from dihydroprogesterone and dihydrotestosterone (DHT), respectively
physiological function
the enzymatic complex 5alpha-R and 3alpha-HSOR colocalizes in glutamatergic and GABAergic neurons of the cerebral cortex, hippocampus, amygdala and thalamus, suggesting that metabolites so formed are relevant for neurotransmitter synthesis and the modulation of their activity in these cells. The metabolites of progesterone (PROG) and testosterone (T) formed by the action of the enzymatic complex 5alpha-R and 3alpha- or 3beta-HSOR have a profound physiological impact in the nervous system, because they are also ligands for a variety of neuronal and glial receptors that are not directly modulated by PROG and T. The reduced metabolites of PROG are also involved in mood regulation. Actions of progesterone and testosterone metabolites in physiological conditions, overview. The enzyme is involed in regulation of the levels of progesterone and testosterone reduced metabolites in the nervous system. Metabolite of dihydrotestosterone (DHT), 4-androsten-3alpha,17beta-diol, exerts europrotective effects in SH-SY5Y neuronal cells and in primary cortical neurons, inhibiting the phosphorylation of extracellular signal-regulated kinase induced by amyloid beta peptide 1-42. Interestingly, this effect is mediated by both GABA-A receptor-dependent and independent mechanisms
additional information
catalytic tetrad N86-S114-Y155-K159, catalytic roles of P185 and T188 and substrate-binding loop flexibility in 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase. Structurally the substrate-binding loop of the residues, T188-K208, is unresolved, while binding with NAD+ causes the appearance of T188-P191 in the binary complex, functional roles of the flexible substrate-binding loop in conformational changes and enzyme catalysis, overview. Simulated molecular modeling gives results that are consistent with the conformational change in the substrate-binding loop after NAD+ binding. These results indicate that P185, T188 and the flexible substrate-binding loop are involved in binding with the nucleotide cofactor and with androsterone and are also involved in catalysis. Homology structure modeling, overview
additional information
-
residues Ser114, Tyr153, and Lys157 form the catalytic triad. Tyr153 is a catalytic base and Ser114 is a substitute
additional information
AKR1C9 has two substrate binding sites, the steroid binding site and the cofactor binding site
additional information
-
AKR1C14 has two substrate binding sites, the steroid binding and the cofactor binding site
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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). AK1C1_MACFU
323
0
36963
Swiss-Prot
other Location (Reliability: 3)
Q9I1X3_PSEAE
Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)
286
0
30921
TrEMBL
Secretory Pathway (Reliability: 1)
T2HVB4_RABIT
322
0
37018
TrEMBL
other Location (Reliability: 1)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
26400
28000
36790
calculated from predicted DD2 amino acid sequence of 322 residues
36850
calculated from predicted DD4 amino acid sequence of 321 residues
26400
calculated from deduced amino acid sequence comprising 258 residues
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homodimer
monomer
additional information
secondary structures of the wild-type and mutants of P185A, P185G, T188A and T188S 3alpha-HSD/CRs are assessed by CD spectroscopy by measuring the ellipticity in the 190-250 nm range at room temperature
homodimer
non-covalent homodimer, 2 * 23000, about, recombinant enzyme, SDS-PAGE
homodimer
-
non-covalent homodimer, 2 * 23000, about, recombinant enzyme, SDS-PAGE
-
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
3alpha-HSD3-NADP+-progesterone complex and 3alpha-HSD3 mutant V54L-NADP+-progesterone complex, sitting drop vapor diffusion method, room temperature, the reservoir solution contains 100 mM sodium cacodylate, pH 6.0, 200 mM ammonium sulfate, 24-26% w/v PEG 3350, with 0.8 mM progesterone, 3-14 days, X-ray diffraction structure determination and analysis at 2.0-2.2 A resolution, molecular replacement with search model, PDB ID 1J96. Progesterone adopts two different binding modes to form complexes within the wild-type enzyme, with one binding mode similar to the orientation of a bile acid (ursodeoxycholate) in the reported ternary complex of human 3alpha-HSD3-NADP+-ursodeoxycholate and the other binding mode resembling the orientation of 20alpha-OHProg in the ternary complex of human 20alpha-HSD-NADP+-20alpha-OHProg
crystal structure determination and analysis of human 3alpha-HSD3-NADP+-5alpha-androstane-3,17-dione/epiandrosterone complex, which was obtained by co-crystallization with 5alpha-DHT in the presence of NADP+. Although 5alpha-DHT is introduced during the crystallization, oxidoreduction of 5alpha-DHT occurs. The locations of 5alpha-androstane-3,17-dione and epiandrosterone are identified in the steroid-binding sites of two 3alpha-HSD3 molecules per crystal asymmetric unit. 5alpha-androstane-3,17-dione and epiandrosterone are oriented upside-down and flipped relative to each other, providing structural clues for 5alpha-DHT reverse binding in the enzyme with the generation of different products. determination and analysis of human 3alpha-HSD3-NADP+-4-androstene-3,17-dione complex crystal structure
crystal structure of the human 3alpha-HSD type 3 in the ternary complex with testosterone and NADP+ determined by molecular replacement method using the program EPMR, at 1.25-A resolution, binding site analysis
purified recombinant enzyme in ternary complex with NADP+ and one inhibitor, from inhibitors 1-6, 15 mg/ml protein in 10 mM potassium phosphate pH 7.4, 500 mM NaCl, 1 mM ethylenediaminetetraacetic acid, 1 mM dithiothreitol is mixed with crystallization solution containing 0.1 M sodium citrate, pH 5.5, 0.4 M ammonium acetate, 2.5% v/v 2-methyl-2,4-pentanediol, 22-30% w/v PEG 4000 for inhibitors 1-4, and containing 0.1 M HEPES pH 6.5, 0.2 M ammonium dihydrogen phosphate, 20-25% w/v PEG 3350 for inhibitors 5 and 6, X-ray diffraction structure determination analysis at 1.55-2.81 A resolution, modelling
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
P185A
site-directed mutagenesis, analysis of kinetics and structure compared to the wild-type enzyme
P185G
site-directed mutagenesis, analysis of kinetics and structure compared to the wild-type enzyme
T188A
site-directed mutagenesis, analysis of kinetics and structure compared to the wild-type enzyme
T188S
site-directed mutagenesis, analysis of kinetics and structure compared to the wild-type enzyme
W173F/P185W
site-directed mutagenesis, analysis of kinetics and structure compared to the wild-type enzyme
W173F/T188W
site-directed mutagenesis, analysis of kinetics and structure compared to the wild-type enzyme
H216F
-
the mutation decreases 3fold the Km for NADP+. The kinetic constants for bile acids with a 12alpha-hydroxy group are decreased 1.5-7fold and those for the other substrates are increased 1.3-9fold. The mutation decreases the stimulatory effects of the enzyme activity by sulfobromophthalein, clofibric acid and thyroxine, which increases the Km for the coenzyme and substrate of the mutant enzymes more highly than those of the wild type enzyme
H216Y
-
the mutation decreases 3fold the Km for NADP+. The kinetic constants for bile acids with a 12alpha-hydroxy group are decreased 1.5-7fold and those for the other substrates are increased 1.3-9fold. The mutation decreases the stimulatory effects of the enzyme activity by sulfobromophthalein, clofibric acid and thyroxine, which increases the Km for the coenzyme and substrate of the mutant enzymes more highly than those of the wild type enzyme
V54L
site-directed mutagenesis, the change renders the sequence identical to that of human 20-alpha hydroxysteroid dehydrogenase. The V54L mutation directly restricts the steroid binding modes to a unique one, which resembles the orientation of 20alpha-OHProg within human 20alpha-HSD. The kinetic study shows that the V54L mutation significantly decreases the 3alpha-HSD activity for the reduction of 5alpha-dihydrotestosterone, while this mutation enhances the 20alpha-HSD activity to convert progesterone
F217S
mutation converts AKR1C33 into a dually coenzyme-specific form and abolishes the activity towards 3-keto-5beta-cholestanes that are substrates specific to AKR1C33, and markedly decreases the sensitivity to 4-pregnenes
K157A
-
site-directed mutagenesis of a catalytic site residue, the NADH binding affinity of K157A mutant is much lower than that of the wild-type resulting in a decreased kcat
S114A
-
site-directed mutagenesis of a catalytic site residue, the mutant shows higher Km and lower kcat values in both oxidation and reduction reactions compared to wild-type
S114A/Y153A
-
site-directed mutagenesis of a catalytic site residue, the double mutant shows higher Km and a highly reduced kcat values in both oxidation and reduction reactions compared to wild-type
Y153A
-
site-directed mutagenesis of a catalytic site residue, the mutant shows higher Km and lower kcat values in both oxidation and reduction reactions compared to wild-type
additional information
when a specific siRNA is used to suppress 3alpha-HSD3 expression without interfering with 3alpha-HSD4, which shares a highly homologous active site, the 5alpha-DHT concentration increases, whereas MCF-7 cell growth is suppressed. Downregulation of 3alpha-HSD3 decreases MCF-7 breast cancer cell growth
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in one step using metal chelate chromatography, purity of the protein is more than 98%
recombinant C-terminally His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity and anion exchange chromatography, gel fitration, and ultrafiltration
recombinant enzyme from cytosol of COS-1 cells by ultracentrifugation
recombinant enzyme from Escherichia coli strain BL21(DE3)
recombinant GST-tagged enzyme from Escherichia coli strain BL21(DE3)pLysS by glutathione affinity chromatography, cleavage of the tag by thrombin, and anion exchange chromatography
recombinant His-tagged and untagged enzyme from Escherchia coli strain BL21(DE3) nickel affinity chromatography, and by deoxycholic acid affinity chromatography, respectively, the latter to 94-98% purity. Deoxycholic acid is linked to the resin Sepharose 4B with the aid of the spacers as cyanuric chloride and ethanediamine. Adsorption analysis by adapting the adsorption isotherm to a specific binding model, the Scatchard analysis model, overview. Comparison of purification methods between synthetic affinity medium and Ni2+-Sepharose column
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3)
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography to homogeneity
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and dialysis
-
recombinant enzyme from cytosol of COS-1 cells by ultracentrifugation
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
3alpha-HSD/CR gene cloned into pET15b vector with an N-terminal His tag sequence and transformation of Escherichia coli BL21(DE3) pLysS cells
AKR1C1, transient expression in COS-1 cells, and recombinant overexpression in Escherichia coli strain BL21(DE3), quantitative real-time PCR analysis
AKR1C2, transient expression in COS-1 cells, and recombinant overexpression in Escherichia coli strain BL21(DE3), quantitative real-time PCR analysis
AKR1C3, transient expression in COS-1 cells, and recombinant overexpression in Escherichia coli strain BL21(DE3), quantitative real-time PCR analysis
AKR1C4, transient expression in COS-1 cells, and recombinant overexpression in Escherichia coli strain BL21(DE3), quantitative real-time PCR analysis
gene hsdA, recombinant expression of His-tagged and untagged enzyme in Escherchia coli strain BL21(DE3)
overexpression of GST-tagged enzyme in Escherichia coli strain BL21(DE3)pLysS
recombinant expression in mouse PCa cells and of FLAG-AKR1C3 in mouse Rv1 cells, recombinant expression of His-tagged AKR1C3 in Escherichia coli strain BL21
recombinant expression of C-terminally His6-tagged enzyme in Escherichia coli strain BL21(DE3)
recombinant expression of His-tagged enzyme in Escherichia coli strain BL21(DE3)
recombinant expression of N-terminally His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3). The N-terminal His-tag has little effect on the enzyme function
-
recombinant His-tagged enzyme overexpression in Escherichia coli strain BL21(DE3)
sequence comparison and phylogenetic analysis, recombinant expression of His-tagged enzyme in Escherichia coli strain BL21(DE3)
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
liver X receptor alpha binds specifically to the liver X receptor alpha response element and mediates transcriptional activation of the AKR1C4 gene. Liver X receptor ligand T1317 induces isoform AKR1C4 expression approximately 2.3fold
-
R1881 treatment decreases AKR1C3 transcripts by about 1.5fold in Rv1 cells, AKR1C3 transcripts are androgen-repressed
the enzyme is induced in the presence of testosterone and progesterone due to the steroids preventing repressor repA from binding the regulatory regions
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
testosterone is converted to 5alpha-dihydrotestosterone, which is present at high concentrations in patients with castration resistant prostate cancer (CRPC). Inhibition of 17beta-HSD5 is therefore considered to be a promising therapy for treating CRPC. High-throughput inhibitor screening, overview
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Trauger, J.W.; Jiang, A.; Stearns, B.A.; LoGrasso, P.V.
Kinetics of allopregnanolone formation catalyzed by human 3alpha-hydroxysteroid dehydrogenase type III (AKR1C2)
Biochemistry
41
13451-13459
2002
Homo sapiens (P52895), Homo sapiens
brenda
Stayrook, K.R.; Rogers, P.M.; Savkur, R.S.; Wang, Y.; Su, C.; Varga, G.; Bu, X.; Wei, T.; Nagpal, S.; Liu, X.S.; Burris, T.P.
Regulation of human 3 alpha-hydroxysteroid dehydrogenase (AKR1C4) expression by the liver X receptor alpha
Mol. Pharmacol.
73
607-612
2008
Homo sapiens
brenda
Oppermann, U.C.; Maser, E.
Characterization of a 3 alpha-hydroxysteroid dehydrogenase/carbonyl reductase from the gram-negative bacterium Comamonas testosteroni
Eur. J. Biochem.
241
744-749
1996
Comamonas testosteroni (P80702), Comamonas testosteroni, Comamonas testosteroni ATCC 11996 (P80702), Comamonas testosteroni ATCC 11996, Pseudomonas sp. (P80701)
brenda
Deyashiki, Y.; Ogasawara, A.; Nakayama, T.; Nakanishi, M.; Miyabe, Y.; Sato, K.; Hara, A.
Molecular cloning of two human liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isoenzymes that are identical with chlordecone reductase and bile-acid binder
Biochem. J.
299
545-552
1994
Homo sapiens (P52895), Homo sapiens (P17516)
brenda
Shiraishi, H.; Ishikura, S.; Matsuura, K.; Deyashiki, Y.; Ninomiya, M.; Sakai, S.; Hara, A.
Sequence of the cDNA of a human dihydrodiol dehydrogenase isoform (AKR1C2) and tissue distribution of its mRNA
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Homo sapiens
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Homo sapiens (P52895)
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Homo sapiens (Q04828)
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Homo sapiens (P42330)
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Endo, S.; Matsunaga, T.; Ikari, A.; El-Kabbani, O.; Hara, A.; Kitade, Y.
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Oryctolagus cuniculus (T2HVB4), Oryctolagus cuniculus
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Human 3alpha-hydroxysteroid dehydrogenase type 3: structural clues of 5alpha-DHT reverse binding and enzyme down-regulation decreasing MCF7 cell growth
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Homo sapiens (P52895)
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Homo sapiens (P42330)
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Comamonas testosteroni (P80702), Comamonas testosteroni ATCC 11996 (P80702)
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The catalytic roles of P185 and T188 and substrate-binding loop flexibility in 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase from Comamonas testosteroni
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Comamonas testosteroni (P80702)
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Chen, J.; Gao, X.; Hong, L.; Ma, L.; Li, Y.
Expression, purification and functional characterization of a novel 3alpha-hydroxysteroid dehydrogenase from Pseudomonas aeruginosa
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Pseudomonas aeruginosa (Q9I1X3)
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Hwang, C.C.; Chang, P.R.; Wang, T.P.
Contribution of remote substrate binding energy to the enzymatic rate acceleration for 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase
Chem. Biol. Interact.
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Comamonas testosteroni (P80702)
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Shiota, A.; Inaba, S.; Oda, M.
Effects of active site residues of 3alpha-hydroxysteroid dehydrogenase from Pseudomonas sp. b-0831 on its catalysis and cofactor binding
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Pseudomonas sp. B-0831
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Hwang, C.C.; Chang, P.R.; Hsieh, C.L.; Chou, Y.H.; Wang, T.P.
Thermodynamic analysis of remote substrate binding energy in 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase catalysis
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Comamonas testosteroni (P80702)
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Wan, R.; Kong, X.; Yang, Y.; Tao, S.; Chen, Y.; Teichmann, A.T.; Wieland, F.H.
Role of human 3alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C3) in the extrahepatic metabolism of the steroidal aromatase inactivator Formestane
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2020
Homo sapiens (P52895), Homo sapiens (Q04828), Homo sapiens (P42330), Homo sapiens (P17516)
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Wu, Y.; Li, L.; Zhou, S.; Shen, Q.; Lin, H.; Zhu, Q.; Sun, J.; Ge, R.S.
Apigenin inhibits rat neurosteroidogenic 5alpha-reductase 1 and 3alpha-hydroxysteroid dehydrogenase
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Rattus norvegicus (P23457)
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Homo sapiens (Q04828), Mus musculus (Q91WT7), Rattus norvegicus (P23457)
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Mao, B.; Wu, C.; Zheng, W.; Shen, Q.; Wang, Y.; Wang, Q.; Lin, H.; Li, X.; Sun, J.; Ge, R.S.
Methoxychlor and its metabolite HPTE inhibit rat neurosteroidogenic 3alpha-hydroxysteroid dehydrogenase and retinol dehydrogenase 2
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684
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Rattus norvegicus
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