HOME
login
history
all enzymes
BRENDA home
History
Information on EC 1.1.1.357 - 3alpha-hydroxysteroid 3-dehydrogenase
for references in articles please use BRENDA:EC1.1.1.357Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
1.1.1.357 3alpha-hydroxysteroid 3-dehydrogenaseIUBMB Comments
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)].
Specify your search results
Word Map
- 1.1.1.357
- ileal
-
ibabp
-
farnesoid
-
enterohepatic
-
sodium-dependent
- 3alpha-hydroxysteroids
- glycocholate
- akr1c2
- 3alpha-hsds
- cyp7a1
-
7alpha-hydroxylase
- glycochenodeoxycholate
- drug development
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
bile acid binding protein, akr1c33, 3alpha-hsd type iii, type 1 3alpha-hsd, 3alpha-hydroxysteroid dehydrogenase type iii, hsd 28, dihydrodiol dehydrogenase 4, 
more
topPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
3alpha-HSD
3alpha-HSD/CR
3alpha-HSD3
3alpha-hydroxysteroid dehydrogenase
3alpha-hydroxysteroid dehydrogenase/carbonyl reductase
AKR1C2
AKR1C4
DD2
HSD 28
hsdA
type 3 3alpha-hydroxysteroid dehydrogenase
3alpha-hydroxysteroid dehydrogenase/carbonyl reductase
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PATHWAY SOURCE
PATHWAYS
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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)].
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
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+
-
-
-
-
?
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)+
3alpha-androstanediol + NAD(P)+
5alpha-dihydrotestosterone + NAD(P)H + H+
-
-
-
-
r
5alpha-androstan-17-beta-ol-3-one + NADH + H+
5alpha-androstane-3alpha,17beta-diol + NAD+
NADH is not a substrate for wild-type
-
-
r
5alpha-androstan-17-beta-ol-3-one + NADPH + H+
5alpha-androstane-3alpha,17beta-diol + NADP+
-
-
-
r
5alpha-androstan-3alpha-ol-17-one + NADP+
(5alpha)-androstan-3,17-dione + NADPH + H+
-
-
-
-
?
5alpha-androstane-3alpha,17beta-diol + NAD+
5alpha-androstan-17-beta-ol-3-one + NADH + H+
-
-
-
r
5alpha-androstane-3alpha,17beta-diol + NADP+
(5alpha)-androstan-17-beta-ol-3-one + NADPH + H+
-
-
-
-
?
5alpha-androstane-3alpha,17beta-diol + NADP+
5alpha-androstan-17-beta-ol-3-one + NADPH + H+
-
-
-
r
5alpha-dihydroprogesterone + NADPH + H+
allopregnanolone + 5alpha,20alpha-tetrahydroprogesterone + NADP+
-
-
-
r
5alpha-pregnan-20alpha-ol-3-one + NADP+
5alpha-pregnane-3,20-dione + NADPH + H+
-
-
-
r
5beta-androstan-3,17-dione + NADPH + H+
5beta-androstan-3alpha-ol-17-one + NADP+
-
-
-
r
5beta-androstan-3alpha-ol-17-one + NADP+
(5beta)-androstan-3,17-dione + NADPH + H+
-
-
-
-
?
5beta-androstan-3alpha-ol-17-one + NADP+
5beta-androstan-3,17-dione + NADPH + H+
-
-
-
r
5beta-androstane-3alpha,17beta-diol + NADP+
5beta-androstan-17beta-ol-3-one + NADPH + H+
-
-
-
-
?
5beta-pregnane-3,20-dione + NADPH + H+
5beta-pregnan-20alpha-ol-3-one + NADP+
-
-
-
r
5beta-pregnane-3alpha,20alpha-diol + NADP+
(5beta)-pregnan-20alpha-ol-3-one + NADPH + H+
-
-
-
-
?
7alpha,12alpha-dihydroxy-5beta-cholestan-3-one + NAD(P)+
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestane + NAD(P)H + H+
-
-
-
-
?
allopregnanolone + 5alpha,20alpha-tetrahydroprogesterone + NADP+
5alpha-dihydroprogesterone + NADPH + H+
-
-
-
r
androstandiol + NAD(P)+
(5alpha,17beta)-17-hydroxyandrostan-3-one + NAD(P)H + H+
-
-
-
?
androstandione + NAD(P)H + H+
3-hydroxyandrostan-17-one + NAD(P)+
-
-
-
?
chenodeoxycholic acid + NADP+
(5beta,7alpha,8xi)-7-hydroxy-3-oxocholan-24-oic acid + NADPH + H+
-
-
-
?
cholate + NAD+
7alpha,12alpha-dihydroxy-3-oxo-5beta-cholan-24-oic acid + NADH + H+
-
-
-
r
cholic acid + NAD(P)+
(5beta,7alpha,8xi,12alpha)-7,12-dihydroxy-3-oxocholan-24-oic acid + NAD(P)H + H+
dihydrotestosterone + NAD(P)H + H+
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
-
-
-
-
?
epiandrosterone + NAD(P)+
(5alpha)-androstane-3,17-dione + NAD(P)H + H+
-
-
-
?
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+
-
-
-
?
pregn-4-en-3,20-dione + NADPH + H+
3alpha-hydroxypregn-4-en-20-one + NADP+
-
-
-
r
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)+
2-(1-imidazolyl)-1-(4-methoxyphenyl)-2-methyl-1-propanone i.e. NKI 42255
-
-
?
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)+
2-(1-imidazolyl)-1-(4-methoxyphenyl)-2-methyl-1-propanone i.e. NKI 42255
-
-
?
3-dehydro-alpha-ecdysone + NAD(P)H + H+
alpha-ecdysone + NAD(P)+
-
-
-
?
3-dehydro-alpha-ecdysone + NAD(P)H + H+
alpha-ecdysone + NAD(P)+
-
-
-
?
3-dehydro-alpha-ecdysone + NAD(P)H + H+
alpha-ecdysone + NAD(P)+
-
-
-
?
3-dehydro-beta-ecdysone + NAD(P)H + H+
beta-ecdysone + NAD(P)+
-
-
-
?
3-dehydro-beta-ecdysone + NAD(P)H + H+
beta-ecdysone + NAD(P)+
-
-
-
?
3alpha-hydroxydesogestrel + NAD(P)+
3-oxodesogestrel + NAD(P)H + H+
-
-
-
?
3alpha-hydroxydesogestrel + NAD(P)+
3-oxodesogestrel + NAD(P)H + H+
-
-
-
?
4-nitroacetophenone + NAD(P)H + H+
1-(4-nitrophenyl)ethanol + NAD(P)+
-
-
-
?
4-nitroacetophenone + NAD(P)H + H+
1-(4-nitrophenyl)ethanol + NAD(P)+
-
-
-
?
4-nitrobenzaldehyde + NAD(P)H + H+
(4-nitrophenyl)methanol + NAD(P)+
-
-
-
?
4-nitrobenzaldehyde + NAD(P)H + H+
(4-nitrophenyl)methanol + NAD(P)+
-
-
-
?
5alpha-dihydrotestosterone + NAD(P)H + H+
(5alpha,17beta)-androstane-3,17-diol + NAD(P)+
-
-
-
?
5alpha-dihydrotestosterone + NAD(P)H + H+
(5alpha,17beta)-androstane-3,17-diol + NAD(P)+
-
-
-
?
5alpha-dihydrotestosterone + NAD(P)H + H+
3alpha-androstanediol + NAD(P)+
-
-
-
-
?
5alpha-dihydrotestosterone + NAD(P)H + H+
3alpha-androstanediol + NAD(P)+
-
-
-
-
r
5alpha-dihydrotestosterone + NADPH + H+
3alpha-androstanediol + NADP+
-
physiological inactivation of the most potent androgen 5alpha dihydrotestosterone
-
-
r
5alpha-dihydrotestosterone + NADPH + H+
5alpha-androstane-3alpha,17beta-diol + NADP+
-
-
-
r
5alpha-dihydrotestosterone + NADPH + H+
5alpha-androstane-3alpha,17beta-diol + NADP+
-
-
-
r
5beta-dihydrotestosterone + NAD(P)H + H+
(5beta,17beta)-androstane-3,17-diol + NAD(P)+
-
-
-
?
5beta-dihydrotestosterone + NAD(P)H + H+
(5beta,17beta)-androstane-3,17-diol + NAD(P)+
-
-
-
?
a 3alpha-hydroxysteroid + NAD(P)+
a 3-oxosteroid + NAD(P)H + H+
-
-
-
?
a 3alpha-hydroxysteroid + NAD(P)+
a 3-oxosteroid + NAD(P)H + H+
-
-
-
?
a 3alpha-hydroxysteroid + NAD(P)+
a 3-oxosteroid + NAD(P)H + H+
-
-
-
?
a 3alpha-hydroxysteroid + NAD+
a 3-oxosteroid + NADH + H+
-
-
-
-
r
a 3alpha-hydroxysteroid + NAD+
a 3-oxosteroid + NADH + H+
-
-
-
r
androsterone + NAD(P)+
(5alpha)-androstane-3,17-dione + NAD(P)H + H+
-
-
-
?
androsterone + NAD(P)+
(5alpha)-androstane-3,17-dione + NAD(P)H + H+
-
-
-
?
androsterone + NAD+
5alpha-androstan-3,17-dione + NADH + H+
-
-
-
-
r
androsterone + NAD+
5alpha-androstan-3,17-dione + NADH + H+
-
rate-limiting step in the reaction is the release of NADH
-
-
r
cholic acid + NAD(P)+
(5beta,7alpha,8xi,12alpha)-7,12-dihydroxy-3-oxocholan-24-oic acid + NAD(P)H + H+
-
-
-
?
cholic acid + NAD(P)+
(5beta,7alpha,8xi,12alpha)-7,12-dihydroxy-3-oxocholan-24-oic acid + NAD(P)H + H+
-
-
-
?
deoxycholic acid + NADH
12alpha-hydroxy-3-oxo-5beta-cholan-24-oic acid + NAD+
-
-
-
-
r
deoxycholic acid + NADH
12alpha-hydroxy-3-oxo-5beta-cholan-24-oic acid + NAD+
-
-
-
-
r
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 + 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+
-
-
-
-
?
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+
-
-
-
-
?
metyrapone + NAD(P)H + H+
2-methyl-1,2-di(pyridin-3-yl)propan-1-ol + NAD(P)+
-
-
-
?
metyrapone + NAD(P)H + H+
2-methyl-1,2-di(pyridin-3-yl)propan-1-ol + NAD(P)+
-
-
-
?
additional information
?
-
-
no activity with testosterone, 3-oxo-desogestrel, progesterone, 4-nitrobenzalcohol, trans-benzene dihydrodiol and cis-benzene dihydrodiol
-
-
?
additional information
?
-
no activity with testosterone, 3-oxo-desogestrel, progesterone, 4-nitrobenzalcohol, trans-benzene dihydrodiol and cis-benzene dihydrodiol
-
-
?
additional information
?
-
-
no activity with testosterone and progesterone
-
-
?
additional information
?
-
-
recombinant 3alpha-HSD/CR protein is active with a variety of C19–27 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, 18–42 microM
-
-
?
additional information
?
-
-
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
-
-
?
additional information
?
-
-
the enzyme catalyzes reversibly the oxidoreduction of 3alpha-hydroxyl groups of steroid hormones
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
no activity with testosterone, 3-oxo-desogestrel, progesterone, 4-nitrobenzalcohol, trans-benzene dihydrodiol and cis-benzene dihydrodiol
-
-
?
additional information
?
-
no activity with testosterone, 3-oxo-desogestrel, progesterone, 4-nitrobenzalcohol, trans-benzene dihydrodiol and cis-benzene dihydrodiol
-
-
?
additional information
?
-
-
no activity with testosterone and progesterone
-
-
?
additional information
?
-
-
recombinant 3alpha-HSD/CR protein is active with a variety of C19–27 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, 18–42 microM
-
-
?
additional information
?
-
-
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
-
-
?
additional information
?
-
-
the enzyme catalyzes reversibly the oxidoreduction of 3alpha-hydroxyl groups of steroid hormones
-
-
-
additional information
?
-
-
isoform AKR1C2 functions preferentially as a 3-ketosteroid reductase
-
-
-
additional information
?
-
DD2 is an isoenzyme of DD4 sharing 82% amino acid sequence identity
-
-
?
additional information
?
-
DD4 is an isoenzyme of DD2 sharing 82% amino acid sequence identity
-
-
?
additional information
?
-
-
the enzyme also exhibits a weak 17beta-hydroxysteroid dehydrogenase activity transforming androstenedione into testosterone
-
-
?
additional information
?
-
enzyme is strictly NADPH-specific
-
-
-
additional information
?
-
no activity with testosterone, 3-oxo-desogestrel, progesterone, NKI 42255, trans-benzene dihydrodiol and cis-benzene dihydrodiol
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3alpha-androstanediol + NAD(P)+
5alpha-dihydrotestosterone + NAD(P)H + H+
-
-
-
-
r
5alpha-androstane-3alpha,17beta-diol + NADP+
(5alpha)-androstan-17-beta-ol-3-one + NADPH + H+
-
-
-
-
?
5alpha-dihydroprogesterone + NADPH + H+
allopregnanolone + 5alpha,20alpha-tetrahydroprogesterone + NADP+
P52895
-
-
-
r
5alpha-dihydrotestosterone + NADPH + H+
3alpha-androstanediol + NADP+
-
physiological inactivation of the most potent androgen 5alpha dihydrotestosterone
-
-
r
5alpha-dihydrotestosterone + NADPH + H+
5alpha-androstane-3alpha,17beta-diol + NADP+
Q04828
-
-
-
r
5beta-androstan-3alpha-ol-17-one + NADP+
(5beta)-androstan-3,17-dione + NADPH + H+
-
-
-
-
?
5beta-androstane-3alpha,17beta-diol + NADP+
5beta-androstan-17beta-ol-3-one + NADPH + H+
-
-
-
-
?
7alpha,12alpha-dihydroxy-5beta-cholestan-3-one + NAD(P)+
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestane + NAD(P)H + H+
-
-
-
-
?
allopregnanolone + 5alpha,20alpha-tetrahydroprogesterone + NADP+
5alpha-dihydroprogesterone + NADPH + H+
P52895
-
-
-
r
androsterone + NAD+
5alpha-androstan-3,17-dione + NADH + H+
-
-
-
-
r
5alpha-dihydrotestosterone + NAD(P)H + H+
3alpha-androstanediol + NAD(P)+
-
-
-
-
?
5alpha-dihydrotestosterone + NAD(P)H + H+
3alpha-androstanediol + NAD(P)+
-
-
-
-
r
a 3alpha-hydroxysteroid + NAD(P)+
a 3-oxosteroid + NAD(P)H + H+
P80702
-
-
-
?
a 3alpha-hydroxysteroid + NAD(P)+
a 3-oxosteroid + NAD(P)H + H+
P80702
-
-
-
?
a 3alpha-hydroxysteroid + NAD(P)+
a 3-oxosteroid + NAD(P)H + H+
P80701
-
-
-
?
a 3alpha-hydroxysteroid + NAD+
a 3-oxosteroid + NADH + H+
-
-
-
-
r
a 3alpha-hydroxysteroid + NAD+
a 3-oxosteroid + NADH + H+
Q9I1X3
-
-
-
r
additional information
?
-
-
the enzyme catalyzes reversibly the oxidoreduction of 3alpha-hydroxyl groups of steroid hormones
-
-
-
additional information
?
-
-
the enzyme catalyzes reversibly the oxidoreduction of 3alpha-hydroxyl groups of steroid hormones
-
-
-
additional information
?
-
-
isoform AKR1C2 functions preferentially as a 3-ketosteroid reductase
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
no effect by 0.5 mM of Mg2+, Ni2+, and Al3+
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
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
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
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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.
Colonic Neoplasms
The bile acid nuclear receptor FXR and the bile acid binding protein IBABP are differently expressed in colon cancer.
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.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
0.001
5beta-pregnane-3alpha,20alpha-diol
-
native enzyme, at pH 7.4 and 25°C; recombinant enzyme, at pH 7.4 and 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
0.0005
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
0.0244
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
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
1.2
NAD+
-
mutant enzyme H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C; wild type enzyme, in 0.1 M potassium phosphate, pH 7.4, at 25°C
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
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.007
5alpha-Androstan-3alpha-ol-17-one
-
native enzyme, at pH 7.4 and 25°C; recombinant enzyme, at pH 7.4 and 25°C
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
0.087
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
0.03
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
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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 H216F, in 0.1 M potassium phosphate, pH 7.4, at 25°C; mutant enzyme H216Y, 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
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
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
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000037
(5-methyl-1H-indol-2-yl)(4-propylpiperidin-1-yl)methanone
Homo sapiens
-
pH 6.0, 22°C
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
3.94
-
recombinant His-tagged enzyme purified via Ni2+ affinity chromatography, pH 11.0, 25°C
15.4
-
recombinant untagged enzyme purified via deoxycholic acid affinity chromatography, pH 11.0, 25°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
parallel expression of Siah2 and AKR1C3 in human prostate cancer tissues
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
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
evolution
-
the enzyme belongs to the AKR1C subfamily, the members of which catalyze the reduction of ketosteroids and ketoprostaglandins
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
-
enzyme 3alpha-HSD/CR belongs to the short chain dehydrogenase/ reductase (SDR) superfamily
malfunction
-
downregulation of 3alpha-HSD3 decreases MCF-7 breast cancer cell growth
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
-
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
metabolism
-
3alpha-hydroxysteroid dehydrogenase isoform AKR1C4 plays a significant role in bile acid biosynthesis, steroid hormone metabolism, and xenobiotic metabolism
metabolism
-
enzyme is involved in inactivation of steroid hormones
-
physiological function
-
3alpha-hydroxysteroid dehydrogenase type 3 plays an essential role in the inactivation of the most potent androgen 5alpha-dihydrotestosterone
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
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
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
Sequence
Q9I1X3_PSEAE
Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)
286
0
30921
TrEMBL
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
26400
-
calculated from deduced amino acid sequence comprising 258 residues; SDS-PAGE
28000
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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 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) by nickel affinity chromatography
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography to homogeneity
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
-
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 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)
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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, Homo sapiens (P52895)
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, Comamonas testosteroni (P80702), Comamonas testosteroni ATCC 11996, Comamonas testosteroni ATCC 11996 (P80702), 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 (P17516), Homo sapiens (P52895)
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
Biochem. J.
334
399-405
1998
Homo sapiens
brenda
Penning, T.; Burczynski, M.; Jez, J.; Hung, C.; Lin, H.; Ma, H.; Moore, M.; Palackal, N.; Ratnam, K.
Human 3alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily: Functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones
Biochem. J.
351
67-77
2000
Homo sapiens, Homo sapiens (P17516)
brenda
Ohta, T.; Ishikura, S.; Shintani, S.; Usami, N.; Hara, A.
Kinetic alteration of a human dihydrodiol/3alpha-hydroxysteroid dehydrogenase isoenzyme, AKR1C4, by replacement of histidine-216 with tyrosine or phenylalanine
Biochem. J.
352
685-691
2000
Homo sapiens
brenda
Rizner, T.; Lin, H.; Penning, T.
Role of human type 3 3alpha-hydroxysteroid dehydrogenase (AKR1C2) in androgen metabolism of prostate cancer cells
Chem. Biol. Interact.
143-144
401-409
2003
Homo sapiens
brenda
Khanna, M.; Qin, K.N.; Wang, R.W.; Cheng, K.C.
Substrate specificity, gene structure, and tissue-specific distribution of multiple human 3 ?-hydroxysteroid dehydrogenases
J. Biol. Chem.
270
20162-20168
1995
Homo sapiens (P17516), Homo sapiens (P42330)
brenda
Mobus, E.; Maser, E.
Molecular cloning, overexpression, and characterization of steroid-inducible 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase from Comamonas testosteroni. A novel member of the short-chain dehydrogenase/reductase superfamily
J. Biol. Chem.
273
30888-30896
1998
Comamonas testosteroni (P80702), Comamonas testosteroni ATCC 11996 (P80702)
brenda
Nahoum, V.; Gangloff, A.; Legrand, P.; Zhu, D.W.; Cantin, L.; Zhorov, B.S.; Luu-The, V.; Labrie, F.; Breton, R.; Lin, S.X.
Structure of the human 3alpha-hydroxysteroid dehydrogenase type 3 in complex with testosterone and NADP at 1.25-A resolution
J. Biol. Chem.
276
42091-42098
2001
Homo sapiens (P52895)
brenda
Amano, Y.; Yamaguchi, T.; Niimi, T.; Sakashita, H.
Structures of complexes of type 5 17beta-hydroxysteroid dehydrogenase with structurally diverse inhibitors: insights into the conformational changes upon inhibitor binding
Acta Crystallogr. Sect. D
71
918-927
2015
Homo sapiens (P42330)
brenda
Endo, S.; Matsunaga, T.; Ikari, A.; El-Kabbani, O.; Hara, A.; Kitade, Y.
Identification of a determinant for strict NADP(H)-specificity and high sensitivity to mixed-type steroid inhibitor of rabbit aldo-keto reductase 1C33 by site-directed mutagenesis
Arch. Biochem. Biophys.
569
19-25
2015
Oryctolagus cuniculus, Oryctolagus cuniculus (T2HVB4)
brenda
Zhang, B.; Hu, X.; Wang, X.; Theriault, J.; Zhu, D.; Shang, P.; Labrie, F.; Lin, S.
Human 3alpha-hydroxysteroid dehydrogenase type 3: structural clues of 5alpha-DHT reverse binding and enzyme down-regulation decreasing MCF7 cell growth
Biochem. J.
473
1037-1046
2016
Homo sapiens (P52895)
brenda
Fan, L.; Peng, G.; Hussain, A.; Fazli, L.; Guns, E.; Gleave, M.; Qi, J.
The steroidogenic enzyme AKR1C3 regulates stability of the ubiquitin ligase Siah2 in prostate cancer cells
J. Biol. Chem.
290
20865-20879
2015
Homo sapiens (P42330)
brenda
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.
FEHLT
0000
2017
Comamonas testosteroni (P80702)
brenda
Yang, H.; Fang, Y.; Wang, Z.; Zhang, L.
One step affinity recovery of 3alpha-hydroxysteroid dehydrogenase from cloned Escherichia coli
J. Chromatogr.
991
79-84
2015
Comamonas testosteroni (P80702), Comamonas testosteroni ATCC 11996 (P80702)
brenda
Zhang, B.; Zhu, D.W.; Hu, X.J.; Zhou, M.; Shang, P.; Lin, S.X.
Human 3-alpha hydroxysteroid dehydrogenase type 3 (3alpha-HSD3) the V54L mutation restricting the steroid alternative binding and enhancing the 20?-HSD activity
J. Steroid Biochem. Mol. Biol.
141
135-143
2014
Homo sapiens (Q04828)
brenda
Hwang, C.C.; Chang, Y.H.; Lee, H.J.; Wang, T.P.; Su, Y.M.; Chen, H.W.; Liang, P.H.
The catalytic roles of P185 and T188 and substrate-binding loop flexibility in 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase from Comamonas testosteroni
PLoS ONE
8
e63594
2013
Comamonas testosteroni (P80702)
brenda
Chen, J.; Gao, X.; Hong, L.; Ma, L.; Li, Y.
Expression, purification and functional characterization of a novel 3alpha-hydroxysteroid dehydrogenase from Pseudomonas aeruginosa
Protein Expr. Purif.
115
102-108
2015
Pseudomonas aeruginosa (Q9I1X3)
brenda
Select items on the left to see more content.
EXTERNAL LINKS (specific for EC-Number 1.1.1.357)
html completed
Use of this online version of BRENDA is free but requires a license. See terms of use.
Information
