Information on EC 1.1.1.357 - 3alpha-hydroxysteroid 3-dehydrogenase

for references in articles please use BRENDA:EC1.1.1.357
Word Map on EC 1.1.1.357
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Select one or more organisms in this record:


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

EC NUMBER
COMMENTARY hide
1.1.1.357
-
RECOMMENDED NAME
GeneOntology No.
3alpha-hydroxysteroid 3-dehydrogenase
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
brassinosteroid biosynthesis I
-
-
brassinosteroid biosynthesis II
-
-
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)].
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Boehringer patent strain
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
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
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(R)-tetralol + NADP+
? + NADPH + H+
show the reaction diagram
-
-
-
-
?
(S)-1,2,3,4-tetrahydronaphth-1-ol + NADP+
1,2,3,4-tetrahydronaphth-1-one + NADPH + H+
show the reaction diagram
-
-
-
-
?
(S)-indan-1-ol + NADP+
indan-1-one + NADPH + H+
show the reaction diagram
-
-
-
-
?
(S)-tetralol + NADP+
1-tetralone + NADPH + H+
show the reaction diagram
-
-
-
-
?
1-acenaphthenol + NADP+
acenaphthylen-1(2H)-one + NADPH + H+
show the reaction diagram
-
-
-
?
17beta-estradiol + NAD(P)H + H+
estrone + NAD(P)+
show the reaction diagram
-
-
-
-
?
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)+
show the reaction diagram
2-decalol + NAD+
2-decalone + NADH + H+
show the reaction diagram
-
-
-
-
r
20alpha-hydroxyprogesterone + NAD(P)H + H+
progesterone + NAD(P)+
show the reaction diagram
-
-
-
-
?
3-dehydro-alpha-ecdysone + NAD(P)H + H+
alpha-ecdysone + NAD(P)+
show the reaction diagram
3-dehydro-beta-ecdysone + NAD(P)H + H+
beta-ecdysone + NAD(P)+
show the reaction diagram
3alpha-androstanediol + NAD(P)+
5alpha-dihydrotestosterone + NAD(P)H + H+
show the reaction diagram
-
-
-
-
r
3alpha-androstanediol + NAD+
5alpha-dihydrotestosterone + NADH + H+
show the reaction diagram
-
-
-
-
?
3alpha-hydroxydesogestrel + NAD(P)+
3-oxodesogestrel + NAD(P)H + H+
show the reaction diagram
4-nitroacetophenone + NAD(P)H + H+
1-(4-nitrophenyl)ethanol + NAD(P)+
show the reaction diagram
4-nitrobenzaldehyde + NAD(P)H + H+
(4-nitrophenyl)methanol + NAD(P)+
show the reaction diagram
5alpha-androstan-17-beta-ol-3-one + NADH + H+
5alpha-androstane-3alpha,17beta-diol + NAD+
show the reaction diagram
NADH is not a substrate for wild-type
-
-
r
5alpha-androstan-17-beta-ol-3-one + NADPH + H+
5alpha-androstane-3alpha,17beta-diol + NADP+
show the reaction diagram
-
-
-
r
5alpha-androstan-3alpha-ol-17-one + NADP+
(5alpha)-androstan-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
-
?
5alpha-androstane-3,17-dione + NAD(P)H + H+
androsterone + NAD(P)+
show the reaction diagram
-
-
-
-
?
5alpha-androstane-3alpha,17beta-diol + NAD+
5alpha-androstan-17-beta-ol-3-one + NADH + H+
show the reaction diagram
-
-
-
r
5alpha-androstane-3alpha,17beta-diol + NADP+
(5alpha)-androstan-17-beta-ol-3-one + NADPH + H+
show the reaction diagram
-
-
-
-
?
5alpha-androstane-3alpha,17beta-diol + NADP+
5alpha-androstan-17-beta-ol-3-one + NADPH + H+
show the reaction diagram
-
-
-
r
5alpha-dihydroprogesterone + NADPH + H+
allopregnanolone + 5alpha,20alpha-tetrahydroprogesterone + NADP+
show the reaction diagram
-
-
-
r
5alpha-dihydrotestosterone + NAD(P)H + H+
(5alpha,17beta)-androstane-3,17-diol + NAD(P)+
show the reaction diagram
5alpha-dihydrotestosterone + NAD(P)H + H+
3alpha-androstanediol + NAD(P)+
show the reaction diagram
5alpha-dihydrotestosterone + NADPH + H+
3alpha-androstanediol + NADP+
show the reaction diagram
5alpha-dihydrotestosterone + NADPH + H+
5alpha-androstane-3alpha,17beta-diol + NADP+
show the reaction diagram
5alpha-pregnan-20alpha-ol-3-one + NADP+
5alpha-pregnane-3,20-dione + NADPH + H+
show the reaction diagram
-
-
-
r
5beta-androstan-3,17-dione + NADPH + H+
5beta-androstan-3alpha-ol-17-one + NADP+
show the reaction diagram
-
-
-
r
5beta-androstan-3alpha-ol-17-one + NADP+
(5beta)-androstan-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
-
?
5beta-androstan-3alpha-ol-17-one + NADP+
5beta-androstan-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
5beta-androstane-3alpha,17beta-diol + NADP+
5beta-androstan-17beta-ol-3-one + NADPH + H+
show the reaction diagram
-
-
-
-
?
5beta-dihydroprogesterone + NADPH + H+
pregnanolone + NADP+
show the reaction diagram
-
-
-
r
5beta-dihydrotestosterone + NAD(P)H + H+
(5beta,17beta)-androstane-3,17-diol + NAD(P)+
show the reaction diagram
5beta-pregnane-3,20-dione + NADPH + H+
5beta-pregnan-20alpha-ol-3-one + NADP+
show the reaction diagram
-
-
-
r
5beta-pregnane-3alpha,20alpha-diol + NADP+
(5beta)-pregnan-20alpha-ol-3-one + NADPH + H+
show the reaction diagram
-
-
-
-
?
7alpha,12alpha-dihydroxy-5beta-cholestan-3-one + NAD(P)+
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestane + NAD(P)H + H+
show the reaction diagram
-
-
-
-
?
9alpha,11beta-prostaglandin F2 + NADP+
? + NADPH + H+
show the reaction diagram
-
-
-
-
?
a 3-alpha-hydroxysteroid + NAD(P)+
a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
-
-
-
?
a 3alpha-hydroxysteroid + NAD(P)+
a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
a 3alpha-hydroxysteroid + NAD+
a 3-oxosteroid + NADH + H+
show the reaction diagram
allopregnanolone + 5alpha,20alpha-tetrahydroprogesterone + NADP+
5alpha-dihydroprogesterone + NADPH + H+
show the reaction diagram
-
-
-
r
androstandiol + NAD(P)+
(5alpha,17beta)-17-hydroxyandrostan-3-one + NAD(P)H + H+
show the reaction diagram
-
-
-
?
androstandione + NAD(P)H + H+
3-hydroxyandrostan-17-one + NAD(P)+
show the reaction diagram
-
-
-
?
androstenol + NAD+
5alpha-androst-16-en-3-one + NADH + H+
show the reaction diagram
-
-
-
-
r
androsterone + NAD(P)+
(5alpha)-androstane-3,17-dione + NAD(P)H + H+
show the reaction diagram
androsterone + NAD(P)+
5alpha-androstane-3,17-dione + NAD(P)H + H+
show the reaction diagram
-
-
-
-
?
androsterone + NAD+
(5alpha)-androstane-3,17-dione + NADH + H+
show the reaction diagram
-
-
-
-
?
androsterone + NAD+
5alpha-androstan-3,17-dione + NADH + H+
show the reaction diagram
androsterone + NADP+
(5alpha)-androstane-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
-
?
androsterone + NADP+
5alpha-androstane-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
?
chenodeoxycholic acid + NADP+
(5beta,7alpha,8xi)-7-hydroxy-3-oxocholan-24-oic acid + NADPH + H+
show the reaction diagram
-
-
-
?
chenodeoxycholic acid + NADP+
? + NADPH + H+
show the reaction diagram
-
-
-
-
?
cholate + NAD+
7alpha,12alpha-dihydroxy-3-oxo-5beta-cholan-24-oic acid + NADH + H+
show the reaction diagram
-
-
-
r
cholic acid + NAD(P)+
(5beta,7alpha,8xi,12alpha)-7,12-dihydroxy-3-oxocholan-24-oic acid + NAD(P)H + H+
show the reaction diagram
cholic acid + NADP+
? + NADPH + H+
show the reaction diagram
-
-
-
-
?
cyclohexanol + NAD+
cyclohexanone + NADH + H+
show the reaction diagram
-
-
-
-
r
dehydrolithocholic acid + NADPH + H+
?
show the reaction diagram
-
-
-
r
deoxycholic acid + NADH
12alpha-hydroxy-3-oxo-5beta-cholan-24-oic acid + NAD+
show the reaction diagram
deoxycholic acid + NADP+
? + NADPH + H+
show the reaction diagram
-
-
-
-
?
dihydrotestosterone + NAD(P)H + H+
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
show the reaction diagram
-
-
-
-
?
epiandrosterone + NAD(P)+
(5alpha)-androstane-3,17-dione + NAD(P)H + H+
show the reaction diagram
-
-
-
?
estrone + NAD(P)H + H+
17beta-estradiol + NAD(P)+
show the reaction diagram
-
-
-
-
?
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+
show the reaction diagram
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+
show the reaction diagram
lithocholic acid + NADP+
? + NADPH + H+
show the reaction diagram
-
-
-
-
?
metyrapol + NAD(P)+
2-methyl-1,2-di(pyridin-3-yl)propan-1-one + NAD(P)H + H+
show the reaction diagram
-
-
-
?
metyrapone + NAD(P)H + H+
2-methyl-1,2-di(pyridin-3-yl)propan-1-ol + NAD(P)+
show the reaction diagram
pregn-4-en-3,20-dione + NADPH + H+
3alpha-hydroxypregn-4-en-20-one + NADP+
show the reaction diagram
-
-
-
r
progesterone + NAD(P)H + H+
20alpha-hydroxyprogesterone + NAD(P)+
show the reaction diagram
-
-
-
-
?
testosterone + NAD(P)H + H+
DELTA4-androstene-3,17-dione + NAD(P)+
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(R)-tetralol + NADP+
? + NADPH + H+
show the reaction diagram
-
-
-
-
?
(S)-indan-1-ol + NADP+
indan-1-one + NADPH + H+
show the reaction diagram
-
-
-
-
?
(S)-tetralol + NADP+
1-tetralone + NADPH + H+
show the reaction diagram
-
-
-
-
?
17beta-estradiol + NAD(P)H + H+
estrone + NAD(P)+
show the reaction diagram
-
-
-
-
?
20alpha-hydroxyprogesterone + NAD(P)H + H+
progesterone + NAD(P)+
show the reaction diagram
-
-
-
-
?
3alpha-androstanediol + NAD(P)+
5alpha-dihydrotestosterone + NAD(P)H + H+
show the reaction diagram
-
-
-
-
r
5alpha-androstane-3,17-dione + NAD(P)H + H+
androsterone + NAD(P)+
show the reaction diagram
-
-
-
-
?
5alpha-androstane-3alpha,17beta-diol + NADP+
(5alpha)-androstan-17-beta-ol-3-one + NADPH + H+
show the reaction diagram
-
-
-
-
?
5alpha-dihydroprogesterone + NADPH + H+
allopregnanolone + 5alpha,20alpha-tetrahydroprogesterone + NADP+
show the reaction diagram
P52895
-
-
-
r
5alpha-dihydrotestosterone + NAD(P)H + H+
3alpha-androstanediol + NAD(P)+
show the reaction diagram
5alpha-dihydrotestosterone + NADPH + H+
3alpha-androstanediol + NADP+
show the reaction diagram
-
physiological inactivation of the most potent androgen 5alpha dihydrotestosterone
-
-
r
5alpha-dihydrotestosterone + NADPH + H+
5alpha-androstane-3alpha,17beta-diol + NADP+
show the reaction diagram
Q04828
-
-
-
r
5beta-androstan-3alpha-ol-17-one + NADP+
(5beta)-androstan-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
-
?
5beta-androstane-3alpha,17beta-diol + NADP+
5beta-androstan-17beta-ol-3-one + NADPH + H+
show the reaction diagram
-
-
-
-
?
5beta-dihydroprogesterone + NADPH + H+
pregnanolone + NADP+
show the reaction diagram
P52895
-
-
-
r
7alpha,12alpha-dihydroxy-5beta-cholestan-3-one + NAD(P)+
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestane + NAD(P)H + H+
show the reaction diagram
-
-
-
-
?
a 3alpha-hydroxysteroid + NAD(P)+
a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
a 3alpha-hydroxysteroid + NAD+
a 3-oxosteroid + NADH + H+
show the reaction diagram
allopregnanolone + 5alpha,20alpha-tetrahydroprogesterone + NADP+
5alpha-dihydroprogesterone + NADPH + H+
show the reaction diagram
P52895
-
-
-
r
androsterone + NAD(P)+
5alpha-androstane-3,17-dione + NAD(P)H + H+
show the reaction diagram
-
-
-
-
?
androsterone + NAD+
(5alpha)-androstane-3,17-dione + NADH + H+
show the reaction diagram
-
-
-
-
?
androsterone + NAD+
5alpha-androstan-3,17-dione + NADH + H+
show the reaction diagram
-
-
-
-
r
androsterone + NADP+
(5alpha)-androstane-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
-
?
chenodeoxycholic acid + NADP+
? + NADPH + H+
show the reaction diagram
-
-
-
-
?
cholic acid + NADP+
? + NADPH + H+
show the reaction diagram
-
-
-
-
?
deoxycholic acid + NADP+
? + NADPH + H+
show the reaction diagram
-
-
-
-
?
estrone + NAD(P)H + H+
17beta-estradiol + NAD(P)+
show the reaction diagram
-
-
-
-
?
lithocholic acid + NADP+
? + NADPH + H+
show the reaction diagram
-
-
-
-
?
progesterone + NAD(P)H + H+
20alpha-hydroxyprogesterone + NAD(P)+
show the reaction diagram
-
-
-
-
?
testosterone + NAD(P)H + H+
DELTA4-androstene-3,17-dione + NAD(P)+
show the reaction diagram
-
-
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADP+
NADPH
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Zn2+
activates 1.75fold at 0.5 mM
additional information
no effect by 0.5 mM of Mg2+, Ni2+, and Al3+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
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
17beta-estradiol
-
competitive inhibitor
3,5,3',5'-tetraiodothyropropionic acid
-
competitive inhibitor
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
chenodeoxycholic acid
-
-
Cu2+
67% inhibition at 0.5 mM
Flufenamic acid
Hexestrol
-
-
Ibuprofen
-
-
indomethacin
-
-
lithocholic acid
-
-
Medroxyprogesterone acetate
-
-
NADPH
inhibition pattern is competitive
Phenolphthalein
ursodeoxycholate
-
micromolar inhibitor, competitive inhibitor versus 5alpha-dihydroprogesterone and uncompetitive inhibitor versus NADPH
Ursodeoxycholic acid
-
-
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
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(R)-ibuprofen
-
167% activity at 1 mM
Clofibric acid
-
240% activity at 0.1 mM
D-thyroxine
-
260% activity at 1 mM
L-thyroxine
-
237% activity at 1 mM
Sulfobromophthalein
-
328% activity at 0.005 mM
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.16 - 0.68
(R)-tetralol
0.14 - 0.26
(S)-1,2,3,4-tetrahydronaphth-1-ol
0.146 - 0.52
(S)-indan-1-ol
0.11 - 0.29
(S)-tetralol
1
2-(1-imidazolyl)-1-(4-methoxyphenyl)-2-methyl-1-propanone
-
pH 7.0, temperature not specified in the publication, NAD(P)H
0.6
2-decalol
-
reombinant His-tagged enzyme, pH 10.5, 25C
-
0.025 - 0.028
3-dehydro-alpha-ecdysone
0.035
3-dehydro-beta-ecdysone
-
pH 7.0, temperature not specified in the publication, NAD(P)H
0.0105
3alpha-androstanediol
-
isoform AKR1C4, at pH 7.4 and 25C
0.0152 - 0.0216
3alpha-hydroxydesogestrel
0.9 - 1
4-Nitroacetophenone
1 - 1.09
4-Nitrobenzaldehyde
0.0001 - 0.003
5alpha-androstan-17-beta-ol-3-one
0.002 - 0.0022
5alpha-Androstan-3alpha-ol-17-one
0.00144
5alpha-androstane-3,17-dione
-
isoform AKR1C4, at pH 7.4 and 25C
0.0008 - 0.0031
5alpha-androstane-3alpha,17beta-diol
0.0018
5alpha-dihydroprogesterone
-
in 100 mM potassium phosphate, pH 7.0, at 25C
0.0012 - 0.07103
5alpha-dihydrotestosterone
0.0002 - 0.0003
5alpha-pregnan-20alpha-ol-3-one
0.0006 - 0.003
5beta-androstan-3,17-dione
0.0006 - 0.0021
5beta-Androstan-3alpha-ol-17-one
0.0012 - 0.0022
5beta-androstane-3alpha,17beta-diol
0.0111 - 0.0201
5beta-dihydrotestosterone
0.0005 - 0.0023
5beta-pregnane-3,20-dione
0.001
5beta-pregnane-3alpha,20alpha-diol
-
native enzyme, at pH 7.4 and 25C; recombinant enzyme, at pH 7.4 and 25C
0.208 - 0.22
9alpha,11beta-prostaglandin F2
0.0015
allopregnanolone
-
in 100 mM potassium phosphate, pH 7.0, at 25C
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
0.0012
androstenol
-
reombinant His-tagged enzyme, pH 10.5, 25C
-
0.0005 - 0.0267
androsterone
0.0011 - 0.0029
chenodeoxycholic acid
0.025 - 0.059
cholic acid
27
Cyclohexanol
-
reombinant His-tagged enzyme, pH 10.5, 25C
0.0009 - 0.004
Dehydrolithocholic acid
0.0013 - 0.0097
deoxycholic acid
0.0011
dihydrotestosterone
-
pH 7.5, 37C
0.0207
epiandrosterone
-
pH 8.9, temperature not specified in the publication, NAD(P)+
0.003 - 0.0068
Fusidic acid
0.001 - 0.0019
lithocholic acid
2.1
metyrapol
-
pH 8.9, temperature not specified in the publication, NAD(P)+
0.61 - 0.63
Metyrapone
0.081 - 1.2
NAD+
0.033
NADH
mutant F217S, pH 7.4, 25C
0.0002 - 0.017
NADP+
0.00007 - 0.009
NADPH
0.00084 - 0.00213
pregn-4-en-3,20-dione
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.18 - 0.77
(R)-tetralol
0.2 - 0.27
(S)-1,2,3,4-tetrahydronaphth-1-ol
0.1 - 0.4
(S)-indan-1-ol
0.2 - 0.43
(S)-tetralol
2.2
2-decalol
-
reombinant His-tagged enzyme, pH 10.5, 25C
-
0.035
3alpha-androstanediol
-
isoform AKR1C4, at pH 7.4 and 25C
0.004 - 0.367
5alpha-androstan-17-beta-ol-3-one
0.007
5alpha-Androstan-3alpha-ol-17-one
-
native enzyme, at pH 7.4 and 25C; recombinant enzyme, at pH 7.4 and 25C
0.03
5alpha-androstane-3,17-dione
-
isoform AKR1C4, at pH 7.4 and 25C
0.087 - 0.35
5alpha-androstane-3alpha,17beta-diol
0.003
5alpha-dihydroprogesterone
-
in 100 mM potassium phosphate, pH 7.0, at 25C
0.033 - 0.1153
5alpha-dihydrotestosterone
0.0025 - 0.05
5alpha-pregnan-20alpha-ol-3-one
0.009 - 0.14
5beta-androstan-3,17-dione
0.004 - 0.18
5beta-Androstan-3alpha-ol-17-one
0.047 - 0.3
5beta-androstane-3alpha,17beta-diol
0.007 - 0.053
5beta-pregnane-3,20-dione
0.002 - 0.003
5beta-pregnane-3alpha,20alpha-diol
0.083 - 0.42
9alpha,11beta-prostaglandin F2
0.000017
allopregnanolone
-
in 100 mM potassium phosphate, pH 7.0, at 25C
230
androstenol
-
reombinant His-tagged enzyme, pH 10.5, 25C
-
0.023 - 500
androsterone
0.032 - 0.13
chenodeoxycholic acid
0.03 - 0.2
cholic acid
2.5
Cyclohexanol
-
reombinant His-tagged enzyme, pH 10.5, 25C
0.006 - 0.037
Dehydrolithocholic acid
0.012 - 0.085
deoxycholic acid
0.025
dihydrotestosterone
-
pH 7.5, 37C
0.032 - 0.043
lithocholic acid
0.2 - 0.58
NAD+
0.006 - 0.85
NADP+
0.01 - 0.1
NADPH
0.0035 - 0.0392
pregn-4-en-3,20-dione
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
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1 - 1.2
(R)-tetralol
0.68 - 1
(S)-indan-1-ol
1.2 - 1.83
(S)-tetralol
3.7
2-decalol
-
reombinant His-tagged enzyme, pH 10.5, 25C
-
3.33
3alpha-androstanediol
-
isoform AKR1C4, at pH 7.4 and 25C
20.72
5alpha-androstane-3,17-dione
-
isoform AKR1C4, at pH 7.4 and 25C
10.3 - 135
5alpha-androstane-3alpha,17beta-diol
1.623 - 28.07
5alpha-dihydrotestosterone
53.3 - 101.7
5beta-Androstan-3alpha-ol-17-one
191667
androstenol
-
reombinant His-tagged enzyme, pH 10.5, 25C
-
4.6 - 178571
androsterone
28.3 - 46.7
chenodeoxycholic acid
1 - 3.3
cholic acid
0.1
Cyclohexanol
-
reombinant His-tagged enzyme, pH 10.5, 25C
8.8 - 14.2
deoxycholic acid
22.7
dihydrotestosterone
-
pH 7.5, 37C
21.7 - 31.7
lithocholic acid
166.7 - 583.3
NAD+
23.3 - 500
NADP+
9 - 27
NADPH
4.167 - 18.4
pregn-4-en-3,20-dione
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
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000015 - 0.0046
NADPH
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0028
(3,6-dihydropyridin-1(2H)-yl)(1H-indol-2-yl)methanone
Homo sapiens
-
pH 6.0, 22C
0.000037
(5-methyl-1H-indol-2-yl)(4-propylpiperidin-1-yl)methanone
Homo sapiens
-
pH 6.0, 22C
0.0029
3-pentyl-2-[[(pyridin-2-yl)methyl]sulfanyl]-7-(pyrrolidine-1-carbonyl)quinazolin-4(3H)-one
Homo sapiens
-
pH 6.0, 22C
0.0026
4-chloro-N-[(4-chlorophenyl)methyl]-5-nitro-1H-pyrazole-3-carboxamide
Homo sapiens
-
pH 6.0, 22C
0.00049
4-nitro-2-([4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]methyl)phenol
Homo sapiens
-
pH 6.0, 22C
0.00029
5-(benzenesulfonyl)-2-nitrophenol
Homo sapiens
-
pH 6.0, 22C
0.00013 - 0.00015
chenodeoxycholic acid
0.0007 - 0.0009
Flufenamic acid
0.0028 - 0.0035
Hexestrol
0.0069 - 0.01
Ibuprofen
0.07 - 0.075
indomethacin
0.00007 - 0.00008
lithocholic acid
0.0016 - 0.0017
Medroxyprogesterone acetate
0.012 - 0.018
Phenolphthalein
0.00006 - 0.00008
Ursodeoxycholic acid
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
3.94
-
recombinant His-tagged enzyme purified via Ni2+ affinity chromatography, pH 11.0, 25C
15.4
-
recombinant untagged enzyme purified via deoxycholic acid affinity chromatography, pH 11.0, 25C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6
-
assay at
7.4
assay at
9 - 10.5
-
assay at
10.5
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4 - 11
activity range, profile overview
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
-
assay at
30
recombinant enzyme
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
15 - 45
optimum at 30C, over 60% of maximal activity in the range of 25-45C, with the temperature increasing from 30C to 45C, the enzyme activity gradually decreases to 77.55% of the optimum whereas with the temperature decreasing from 30C to 15C, the enzyme activity rapidly drops to 39.4% of the optimum
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
-
Manually annotated by BRENDA team
-
parallel expression of Siah2 and AKR1C3 in human prostate cancer tissues
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
26400
-
calculated from deduced amino acid sequence comprising 258 residues; SDS-PAGE
36000
-
x * 36000, SDS-PAGE
36790
-
calculated from predicted DD2 amino acid sequence of 322 residues
36850
-
calculated from predicted DD4 amino acid sequence of 321 residues
37000
-
purified DD2
39000
-
purified DD4
56000
-
about, gel filtration, recombinant enzyme
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
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
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
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
40
purified recombinant His-tagged enzyme, stable up to
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
in one step using metal chelate chromatography, purity of the protein is more than 98%
-
Q-Sepharose column chromatography and Sephadex G-100 gel filtration
-
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 AKR1C3 from Escherichia coli strain BL21
-
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
-
recombinant wild-type and mutant enzymes
-
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
-
expressed in COS-1 cells, PC-3 cells, and LNCaP cells
-
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Escherichia coli cells
-
expressed in Escherichia coli JM109 cells
-
expressed in Huh-7 and Hep-G2 cells
-
gene hsdA, recombinant expression of His-tagged and untagged enzyme in Escherchia coli strain BL21(DE3)
-
overexpression in Escherichia coli; overexpression in Escherichia coli
-
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 wild-type and mutant enzymes
-
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)
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
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
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
H216L
-
inactive
H216W
-
inactive
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
N272T
mutation does not influence cofactor specificity
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
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
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