Information on EC 1.1.1.149 - 20alpha-hydroxysteroid dehydrogenase

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

EC NUMBER
COMMENTARY hide
1.1.1.149
-
RECOMMENDED NAME
GeneOntology No.
20alpha-hydroxysteroid dehydrogenase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
17alpha,20alpha-dihydroxypregn-4-en-3-one + NAD(P)+ = 17alpha-hydroxyprogesterone + NAD(P)H + H+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Steroid hormone biosynthesis
-
-
SYSTEMATIC NAME
IUBMB Comments
20alpha-hydroxysteroid:NAD(P)+ 20-oxidoreductase
Re-specific with respect to NAD(P)+ (cf. EC 1.1.1.62 17beta-estradiol 17-dehydrogenase).
CAS REGISTRY NUMBER
COMMENTARY hide
9040-08-8
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
female Shiba goats, 2-4 years old
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Balb/c mice
-
-
Manually annotated by BRENDA team
female, Wistar-Imamichi strain
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
the enzyme regulates mechanisms involved in the maintenance of early pregnancy
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(S)-tetralol + NAD(P)+
(S)-tetralone + NAD(P)H + H+
show the reaction diagram
-
-
-
-
?
1-acenaphthenol + NAD+
? + NADH + H+
show the reaction diagram
-
-
-
-
?
1-phenyl-1,2-propanedione + NADPH
NADP+ + ?
show the reaction diagram
11-deoxycorticosterone + NAD(P)H
4-pregnen-20alpha,21-diol-3-one + NAD(P)+
show the reaction diagram
11-deoxycortisol + NADH
? + NAD+
show the reaction diagram
17alpha,20alpha-dihydroxypregn-4-en-3-one + NAD(P)+
17alpha-hydroxyprogesterone + NAD(P)H
show the reaction diagram
17alpha,21-dihydroxyadrenocorticosteroid + NAD(P)H
? + NADP+
show the reaction diagram
-
NADH preferred
-
?
17alpha-hydroxycorticosterone + NADPH
? + NADP+
show the reaction diagram
-
less reactive than with 17alpha-hydroxyrogesterone
-
?
17alpha-hydroxypregnenolone + NADPH
? + NADP+
show the reaction diagram
17alpha-hydroxyprogesterone + NAD(P)H
17alpha,20alpha-dihydroxypregn-4-en-3-one + NAD(P)+
show the reaction diagram
17alpha-hydroxyprogesterone + NAD(P)H + H+
17alpha,20alpha-dihydroxy-pregn-4-en-3-one + NAD(P)+
show the reaction diagram
17alpha-hydroxyprogesterone + NADPH
17alpha,20alpha-dihydroxyprogesterone + NADP+
show the reaction diagram
17alpha-hydroxyprogesterone + NADPH + H+
17alpha,20alpha-dihydroxy-pregn-4-en-3-one + NADP+
show the reaction diagram
2,3-butanedione + NADPH
? + NADP+
show the reaction diagram
2,3-heptanedione + NADPH
NADP+ + ?
show the reaction diagram
2,3-hexanedione + NADPH
NADP+ + ?
show the reaction diagram
2,3-pentanedione + NADPH
NADP+ + ?
show the reaction diagram
20alpha-dihydroprogesterone + NAD+
progesterone + NADH
show the reaction diagram
-
-
-
?
20alpha-dihydroprogesterone + NADP+
progesterone + NADPH
show the reaction diagram
-
-
-
?
20alpha-hydroxy-5beta-pregnan-3-one + NADP+
5beta-pregnane-3,20-dione + NADPH
show the reaction diagram
-
-
-
?
20alpha-hydroxyprogesterone + NAD+
progesterone + NADH
show the reaction diagram
-
-
-
-
?
20alpha-hydroxyprogesterone + NADP+
progesterone + NADPH
show the reaction diagram
4-nitrobenzaldehyde + NADPH
4-nitrobenzyl alcohol + NADP+
show the reaction diagram
4-pregnen-20alpha-ol-3-one + NAD(P)+
4-pregnen-3,20-dione + NAD(P)H + H+
show the reaction diagram
-
-
-
-
r
5alpha-pregnan-20alpha-ol-3-one + NAD(P)+
5alpha-pregnan-3,20-dione + NAD(P)H
show the reaction diagram
-
-
-
-
r
5alpha-pregnan-20alpha-ol-3-one + NAD(P)+
5alpha-pregnane-3,20-dione + NAD(P)H
show the reaction diagram
-
-
-
-
r
5alpha-pregnan-3alpha-ol-20-one + NAD(P)H
5alpha-pregnan-3alpha,20alpha-diol + NAD(P)+
show the reaction diagram
-
-
-
-
r
5alpha-pregnan-3alpha-ol-20-one + NAD(P)H + H+
5alpha-pregnan-3alpha,20alpha-diol + NAD(P)+
show the reaction diagram
-
-
-
-
r
5alpha-pregnane-21-ol-3,20-dione + NAD(P)H
5alpha-pregnane-20alpha,21-diol-3-one + NAD(P)+
show the reaction diagram
-
-
-
-
r
5alpha-pregnane-3,20-dione + NAD(P)H
5alpha-pregnan-20alpha-ol-3-one + NAD(P)+
show the reaction diagram
-
-
-
-
r
5alpha-pregnane-3alpha,20alpha-diol + NAD(P)+
3alpha-hydroxy-5alpha-pregnan-20-one + NAD(P)H + H+
show the reaction diagram
5alpha-pregnane-3alpha,21-diol-20-one + NAD(P)H + H+
5alpha-pregnane-3alpha,20alpha,21-triol + NAD(P)+
show the reaction diagram
-
-
-
-
r
5beta-dihydrocortisol + NADH
? + NAD+
show the reaction diagram
-
-
-
r
5beta-pregnan-20alpha-ol-3-one + NAD(P)+
5beta-pregnan-3,20-dione + NAD(P)H
show the reaction diagram
-
-
-
-
r
5beta-pregnan-3alpha-ol-20-one + NAD(P)H
5beta-pregnan-3alpha,20alpha-diol + NAD(P)+
show the reaction diagram
-
-
-
-
r
5beta-pregnan-3alpha-ol-20-one + NAD(P)H
5beta-pregnane-3alpha,20alpha-diol + NAD(P)+
show the reaction diagram
-
-
-
-
r
5beta-pregnan-3alpha-ol-20-one + NAD(P)H + H+
5alpha-pregnan-3alpha,20alpha-diol + NAD(P)+
show the reaction diagram
-
-
-
-
?
5beta-pregnane-3,20-dione + NAD(P)H + H+
5alpha-pregnan-20alpha-ol-3-one + NAD(P)+
show the reaction diagram
-
-
-
-
r
5beta-pregnane-3alpha,20alpha-diol + NAD(P)+
5beta-pregnan-20alpha-ol-3-one + NAD(P)H + H+
show the reaction diagram
9,10-phenanthrenequinone + NADPH
NADP+ + ?
show the reaction diagram
-
-
-
-
-
acetoacetyl-CoA + NADPH
NADP+ + ?
show the reaction diagram
benzaldehyde + NADPH
benzyl alcohol + NADP+
show the reaction diagram
-
-
-
-
-
corticosterone + NADPH
? + NADP+
show the reaction diagram
-
less reactive than with 17alpha-hydroxyprogesterone
-
?
cortisol + NADH
20alpha-dihydrocortisol + NAD+
show the reaction diagram
cortisone + NADH
? + NAD+
show the reaction diagram
D-galactose + NADPH
NADP+ + ?
show the reaction diagram
-
-
-
-
-
D-glucose + NADPH
NADP+ + ?
show the reaction diagram
-
-
-
-
-
dihydrotestosterone + NADPH
? + NADP+
show the reaction diagram
-
-
-
-
r
DL-glyceraldehyde + NADPH
glycerol + NADP+
show the reaction diagram
-
-
-
-
-
dydrogesterone + NADH + H+
20alpha-hydroxydydrogesterone + NAD+
show the reaction diagram
-
-
-
-
?
ethyl 2-methylacetoacetate + NADPH
NADP+ + ?
show the reaction diagram
ethyl 4-chloroacetoacetate + NADPH
NADP+ + ?
show the reaction diagram
ethyl acetoaetate + NADPH
(S)-ethyl 3-hydroxybutyrate + NADP+
show the reaction diagram
ethyl pyruvate + NADPH
NADP+ + ?
show the reaction diagram
isatin + NADPH
NADP+ + ?
show the reaction diagram
methylglyoxal + NADPH
NADP+ + ?
show the reaction diagram
progesterone + NAD(P)+
20alpha-hydroxyprogesterone + NAD(P)H + H+
show the reaction diagram
-
-
-
?
progesterone + NAD(P)H
20alpha-hydroxypregn-4-en-3-one + NAD(P)+
show the reaction diagram
progesterone + NAD(P)H
20alpha-hydroxyprogesterone + NAD(P)+
show the reaction diagram
progesterone + NAD(P)H + H+
20alpha-hydroxyprogesterone + NAD(P)+
show the reaction diagram
progesterone + NADH
20alpha-hydroxyprogesterone + NAD+
show the reaction diagram
-
-
-
-
?
progesterone + NADPH
20alpha-hydroxyprogesterone + NADP+
show the reaction diagram
prostaglandin E2 + NADPH
NADP+ + ?
show the reaction diagram
-
low activity
-
-
-
pyridine-3-aldehyde + NADPH
NADP+ + ?
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
17alpha,20alpha-dihydroxypregn-4-en-3-one + NAD(P)+
17alpha-hydroxyprogesterone + NAD(P)H
show the reaction diagram
-
inactive molecule form
hormone
-
r
17alpha-hydroxyprogesterone + NAD(P)H
17alpha,20alpha-dihydroxypregn-4-en-3-one + NAD(P)+
show the reaction diagram
progesterone + NAD(P)+
20alpha-hydroxyprogesterone + NAD(P)H + H+
show the reaction diagram
D0VDT4
-
-
-
?
progesterone + NAD(P)H
20alpha-hydroxypregn-4-en-3-one + NAD(P)+
show the reaction diagram
-
-
-
-
r
progesterone + NAD(P)H + H+
20alpha-hydroxyprogesterone + NAD(P)+
show the reaction diagram
-
maternal and fetal 20alpha-HSD play a role in maintaining normal pregnancy at least partially by reducing progesterone concentrations in fetuses
-
-
?
progesterone + NADPH
20alpha-hydroxyprogesterone + NADP+
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3-acetylpyridine adenine dinucleotide phosphate
-
coenzyme analog
NAD(P)+
NAD(P)H
NADP+
nicotinamide 1,N6-ethenoadenine dinucleotide phosphate
-
coenzyme analog
nicotinamide hypoxanthine dinucleotide phosphate
-
coenzyme analog
thio-NADP+
-
coenzyme analog
additional information
-
nitroblue tetrazolium as hydrogen acceptor
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K+
-
activates
Mn2+
-
required
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,10-phenanthroline
-
50% inhibition at 0.065 mM
1,2-naphthoquinone
-
0.01 mM, 55% inhibition of enzyme in liver, 10% in kidney, 10% in lung cytosolic fraction, respectively
1-phenylcyclopentanecarboxylic acid
-
-
16alpha-Bromoacetoxyprogesterone
-
-
17alpha-hydroxyprogesterone
-
most inhibitory at pH 8.0, significant at pH 6.8
17beta-estradiol
-
20alpha-hydroxyprogesterone analog, competitive or noncompetitive depending on variable substrate
2',5'-adenosine bisphosphate
-
competitive inhibition versus NADP+
2',5'-ADP
-
coenzyme-competitive inhibitor
2'-adenylic acid
-
; coenzyme-competitive inhibitor
2'-phosphoadenosine diphosphoribose
2,4-Pentanedione
-
; pH profile for the inactivation, overview
2-(4-chlorobenzylidene)cyclopentanone
-
-
2-(4-chlorobenzylidene)cyclopentyl ethyl ether
-
-
2-acetylbenzofuran
-
50% inhibition at 0.033 mM
20beta-hydroxypregn-4-en-3-one
-
marginally inhibitory at pH 8.0
3',3'',5',5''-tetrabromophenolphthalein
-
50% inhibition at 33 nM
3',3'',5',5''-tetrabromophenolphthalein diacetate
-
50% inhibition at 350 nM
3',3'',5',5''-tetraiodophenolphthalein
-
50% inhibition at 120 nM
3',5'-cyclic AMP
-
coenzyme-competitive inhibitor
3,5-dibromo-4-hydroxybenzoic acid methyl ester
-
50% inhibition at 0.099 mM
3,5-dibromosalicylic acid
-
-
3,5-dichlorosalicylic acid
3,5-diiodosalicylic acid
-
competitive
3-Aminopyridine 1,N6-ethenoadenine dinucleotide phosphate
-
NADP analog, competitive inhibitor
3-Aminopyridine adenine dinucleotide phosphate
3-bromo-5-phenylsalicylic acid
-
-
3-chloro-5-phenylsalicylic acid
-
-
3-phenyl-5-bromosalicylic acid
-
-
3-phenylcyclopentanecarboxylic acid
-
-
4'-butyl-5-chloro-4-hydroxybiphenyl-3-carboxylic acid
-
7fold selectivity relative to 3alpha-hydroxysteroid dehydrogenase AKR1C2
5'-adenosine diphosphate
-
-
5'-Adenosine triphosphate
-
-
5'-adenylic acid
-
; coenzyme-competitive inhibitor
5'-ADP
-
coenzyme-competitive inhibitor
5'-ATP
-
coenzyme-competitive inhibitor
5-chloro-4-hydroxy-3'-methylbiphenyl-3-carboxylic acid
-
13fold selectivity relative to 3alpha-hydroxysteroid dehydrogenase AKR1C2
5-chloro-4-hydroxy-4'-methylbiphenyl-3-carboxylic acid
-
24fold selectivity relative to 3alpha-hydroxysteroid dehydrogenase AKR1C2
5-chloro-4-hydroxybiphenyl-3-carboxylic acid
-
24fold selectivity relative to 3alpha-hydroxysteroid dehydrogenase AKR1C2
5-fluoro-4-hydroxybiphenyl-3-carboxylic acid
-
1.2fold selectivity relative to 3alpha-hydroxysteroid dehydrogenase AKR1C2
5alpha-dihydrotestosterone
-
-
5beta-dihydrotestosterone
-
-
9,10-phenanthrenequinone
-
0.01 mM, 70% inhibition of enzyme in liver, 5% in kidney, 60% in lung cytosolic fraction, respectively
Acetylsalicylate
-
-
adenosine 2'-monophospho- 5'-diphosphoribose
-
strong inhibition
adenosine diphosphoribose
-
; coenzyme-competitive inhibitor
Ag+
-
very powerful
aminopyridine 1,N6-ethenoadenine dinucleotide phosphate
-
-
aminopyridine adenine dinucleotide phosphate
-
-
androstendione
-
most inhibitory at pH 8.0
apigenin
Barbiturates
-
-
-
benzbromarone
-
50% inhibition at 48 nM
benzbromarone acetate
-
50% inhibition at 430 nM
benzofuran
-
50% inhibition at 1.45 mM
benzofuran-2-carboxylic acid
-
50% inhibition at 0.16 mM
Bethamethasone
-
0.1 mM, 10% inhibition
Bile acids
Bromophenol blue
carboxylic acid
-
competitive for acetic and propionic acid, mixed-type from pentanoic to undecanoic acid with exception of heptanoic acid
cibacron
cloxazolam
-
0.01 mM, 38% inhibition
diazepam
-
50% inhibition at 0.0056 mM
Diazotized 3-aminopyridine 1,N6-ethenoadenine dinucleotide phosphate
-
; NADP+ analog, competitive inhibitor
Diazotized 3-aminopyridine adenine dinucleotide phosphate
-
; NADP analog, competitive inhibitor
dibenzofuran
-
50% inhibition at 0.895 mM
Dienstrol
Diphenic acid
-
less than 17% inhibition
ethyl acetate
fatty acids
fisetin
Flufenamic acid
Fluorescein mercuric acetate
-
-
glycerol
-
inhibition partially reversed by cysteine
glycyrrhetinic acid
-
50% inhibition at 0.0022 mM
Hexestrol
-
50% inhibition at 0.0083 mM
indomethacin
kaempferol
linear monocarboxylic acids
-
slight inhibition, overview
-
linear N-alkylammonium chloride derivatives
-
slight inhibition, overview
-
lithocholic acid
-
50% inhibition at 0.022 mM
luteolin
Maleimide
-
pH profile for the inactivation, overview
Meclofenamic acid
-
20alpha-hydroxyprogesterone oxidation
medazepam
-
50% inhibition at 0.0047 mM
Medroxyprogesterone acetate
-
50% inhibition at 700 nM
Metal ions
-
strong
-
myricetin
-
0.02 mM, 60% inhibition of enzyme in liver cytosolic fraction, 0.05 mM, 10% inhibition in kidney cytosolic fraction
N-1-butylnicotinamide chloride
-
inhibition of the ovarian enzyme, competitive inhibition versus NADP+
N-1-decylnicotinamide chloride
-
inhibition of the ovarian enzyme, mixed type inhibition versus NADP+
N-1-dodecylnicotinamide chloride
-
inhibition of the ovarian enzyme, mixed type inhibition versus NADP+
N-1-ethylnicotinamide chloride
-
inhibition of the ovarian enzyme, competitive inhibition versus NADP+
N-1-heptylnicotinamide chloride
-
inhibition of the ovarian enzyme, competitive inhibition versus NADP+
N-1-hexylnicotinamide chloride
-
inhibition of the ovarian enzyme, competitive inhibition versus NADP+
N-1-methylnicotinamide chloride
-
inhibition of the ovarian enzyme, competitive inhibition versus NADP+
N-1-nonylnicotinamide chloride
-
inhibition of the ovarian enzyme, mixed type inhibition versus NADP+
N-1-octylnicotinamide chloride
-
inhibition of the ovarian enzyme, mixed type inhibition versus NADP+
N-1-pentylnicotinamide chloride
-
inhibition of the ovarian enzyme, competitive inhibition versus NADP+
N-1-propylnicotinamide chloride
-
inhibition of the ovarian enzyme, competitive inhibition versus NADP+
N-1-undecylnicotinamide chloride
-
inhibition of the ovarian enzyme, mixed type inhibition versus NADP+
N-alkylammonium chloride
-
competitive from pentyl to heptyl, mixed type from nonyl to dodecyl
N-Alkylmaleimide
-
N-ethylmaleimide and N-butylmaleimide to N-octylmaleimide at 25C, pH 7.7
N-alkylmaleimides
-
coenzyme-competitive inhibition, varying in chainlength from N-ethyl- to N-octylmaleimide, effectively inactivated the enzyme through pseudo-first-order rate processes, overview
-
N-Butylmaleimide
-
inactivation via sulfhydryl groups of the enzyme in a nonpolar region
N-ethylmaleimide
-
inactivation via sulfhydryl groups of the enzyme in a nonpolar region
N-Heptylmaleimide
-
inactivation via sulfhydryl groups of the enzyme in a nonpolar region
N-Hexylmaleimide
-
inactivation via sulfhydryl groups of the enzyme in a nonpolar region
N-Octylmaleimide
-
inactivation via sulfhydryl groups of the enzyme in a nonpolar region
N-Pentylmaleimide
-
inactivation via sulfhydryl groups of the enzyme in a nonpolar region
N1-alkylnicotinamide chloride
-
competitive from methyl to heptyl, mixed-type from octyl to dodecyl with respect to NADP
NAD+
-
NADP analog, competitive inhibitor
NADH
-
concentrations above 0.1 mM
NADP+
NADPH
-
competitive and noncompetitive product inhibition with respect to NADP+ depending on substrate concentrations
naringenin
natural oestrogens
-
e.g. oestrone less than 15% inhibition
-
o-cresolphthalein
-
50% inhibition at 140 nM
p-chloromercuribenzoate
-
also other sufhydryl reagents like 5,5'-dithiobis-2-nitrobenzoic acid and iodoacetamide strong
phenazine methosulfate
-
0.01-0.3 mg/ml
Phenobarbital
Phenolphthalein
-
50% inhibition at 340 nM
progesterone
prolactin
-
down-regulating of gene-expression
-
pyridoxal 5'-phosphate
-
strong, 90% inactivation by 10 mM
quercetin
quercitrin
salicylate
-
-
sorbinil
Sulfobromophthalein
-
little effect on hepatic NADPH-dependent 20alpha-hydroxysteroid dehydrogenase, potent inhibitor of hepatic NADH-dependent 20alpha-hydroxysteroid dehydrogenase activity
synthetic non-steroidal oestrogens
-
hexoestrol most potent competitive inhibitor
-
synthetic oestrogens
-
e.g. hexestrol, silbestrol, dienstrol
-
Tolrestat
Ursodeoxycholic acid
-
50% inhibition at 0.34 mM
valporic acid
-
less than 17% inhibition
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cysteine
-
restoring, also other sulfhydryl compounds, NADH-linked to a greater extent than the NADPH-linked activity
Dimethyl formamide
-
5-10%
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1 - 1870
(S)-ethyl 3-hydroxybutyrate
4.8 - 5
(S)-methyl 3-hydroxybutyrate
0.007 - 0.47
(S)-tetralol
0.092 - 0.129
1,2-Cyclohexanedione
0.006
1-phenyl-1,2-propanedione
0.0033
11-deoxycorticosterone
-
pH 7.4, 37C
0.073
17-hydroxyprogesterone
-
-
0.013
17alpha,20alpha-dihydroxypregn-4-en-3-one
-
-
0.013 - 0.014
17alpha,20alpha-dihydroxyprogesterone
0.022
17alpha,21-dihydroxy-5beta-pregnan-3,20-dione
-
-
0.02
17alpha,21-dihydroxy-5beta-pregnane-3,11,20-trione
-
-
0.002 - 0.0034
17alpha-hydroxypregnenolone
0.0029 - 0.118
17alpha-hydroxyprogesterone
34.8 - 66.3
2,3-Butanediol
0.015 - 0.018
2,3-Butanedione
0.005 - 0.008
2,3-heptanedione
0.01 - 0.016
2,3-Hexanedione
0.018 - 0.021
2,3-Pentanedione
0.131 - 0.243
2,4-Pentanedione
0.0026
2-amino-8-((2-fluoro-4-methoxybenzyl)thio)-1,9-dihydro-6H-purin-6-one
-
pH 7.0, 25C
0.041
20alpha-dihydrocortisol
-
NAD+, pH 7.9
0.00102 - 0.00516
20alpha-hydroxy-4-pregnen-3-one
0.013
20alpha-hydroxy-5alpha-pregnan-3-one
-
+/-0.0035
0.073
20alpha-hydroxy-5beta-pregnan-3-one
-
-
0.00117 - 2.5
20alpha-hydroxyprogesterone
0.23 - 0.57
3,4-hexanedione
0.00208
3-acetylpyridine adenine dinucleotide phosphate
-
NADP analog
0.012
3alpha-hydroxy-5alpha-pregnan-20-one
-
+/-0.0035
0.221 - 0.3811
4-Nitrobenzaldehyde
0.016
4-pregnen-20alpha-ol-3-one
-
pH 7.0, 25C
0.0007 - 0.0027
5alpha-pregnan-20alpha-ol-3-one
0.002 - 0.0033
5alpha-pregnan-3alpha-ol-20-one
0.0012
5alpha-pregnane-21-ol-3,20-dione
-
pH 7.0, 25C
0.0011
5alpha-pregnane-3,20-dione
-
pH 7.0, 25C
0.0004 - 0.0009
5alpha-pregnane-3alpha,20alpha-diol
0.001 - 0.073
5beta-pregnan-20alpha-ol-3-one
0.0033 - 0.0062
5beta-Pregnan-3alpha-ol-20-one
0.0012
5beta-pregnane-3,20-dione
-
pH 7.0, 25C
0.0015
5beta-pregnane-3alpha,20alpha-diol
-
pH 7.0, 25C
0.00195
9,10-phenanthrenequinone
-
+/-0.0004
0.02 - 0.022
acetoacetyl-CoA
0.186 - 0.272
acetoin
2.1
benzene dihydrodiol
-
-
0.008
benzyl acetoacetate
0.078
Camphorquinone
-
-
2.02 - 2.9
cis-benzene-1,2-dihydrodiol
0.032
cortisol
-
NADH, pH 6.3
0.022
cortisone
-
NADH, pH 6.3
120
D,L-glyceraldehyde
-
-
0.3 - 0.67
D-glyceraldehyde
0.534 - 0.587
D-Lactaldehyde
0.069 - 0.151
dihydrotestosterone
0.852 - 1.3
DL-glyceraldehyde-3-phosphate
0.012 - 0.015
ethyl 2-methylacetoacetate
0.222 - 0.447
ethyl 3-oxovalerate
0.027
ethyl 4-chloroacetoacetate
0.02 - 20
ethyl acetoacetate
0.303 - 0.654
ethyl benzoylacetate
0.025
ethyl pyruvate
0.039 - 0.064
isatin
0.117 - 0.123
methyl acetoacetate
0.356 - 0.548
methylglyoxal
0.004
n-butyl acetoacetate
0.0015 - 0.0024
n-hexyl acetoacetate
0.0013 - 0.0016
n-octyl acetoacetate
0.526
NAD+
-
20alpha-dihydrocortisol
0.0081 - 1.1
NADH
0.0007 - 0.025
NADP+
0.0002 - 0.052
NADPH
0.1429
nicotinamide 1,N6-ethenoadenine dinucleotide phosphate
-
NADP analog
0.0588
nicotinamide hypoxanthine dinucleotide phosphate
-
NADP analog
0.43 - 0.591
Phenylglyoxal
0.0006 - 0.2833
progesterone
0.049 - 0.081
Pyridine-3-aldehyde
0.945 - 1.06
Pyridine-4-aldehyde
0.00186
thionicotinamide adenine dinucleotide phosphate
-
NADP analog
50.9 - 79.7
trans-1S,2S-cyclohexanediol
1.6
trans-benzene-1S,2S-dihydrodiol
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.178
17alpha-hydroxyprogesterone
Rattus norvegicus
-
+/-0.8
0.785
20alpha-hydroxy-5alpha-pregnan-3-one
Rattus norvegicus
-
+/-4.3
0.04 - 1.17
20alpha-hydroxyprogesterone
0.208
3alpha-hydroxy-pregnan-20-one
Rattus norvegicus
-
+/-1.6
5.91
4-Nitrobenzaldehyde
Rattus norvegicus
-
+/-33.4
7.7
9,10-phenanthrenequinone
Rattus norvegicus
-
+/-26.9
0.215
D,L-glyceraldehyde
Rattus norvegicus
-
+/-0.3
1.52
NADP+
Rattus norvegicus
-
+/-6.1
1.43
NADPH
Rattus norvegicus
-
+/-1.3
1.65
progesterone
Rattus norvegicus
-
+/-6.7
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0000008 - 0.000062
(S)-tetralol
3707
0.00004 - 0.00027
5alpha-pregnane-3alpha,20alpha-diol
8574
0.0000007 - 0.000027
5beta-Pregnan-3alpha-ol-20-one
3187
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0358
1-phenylcyclopentanecarboxylic acid
-
pH 6.5, temperature not specified in the publication
0.00134
2',5'-adenosine bisphosphate
-
pH 7.8, 23C
0.148
2'-adenylic acid
-
pH 7.8, 23C
0.0172
2-(4-chlorobenzylidene)cyclopentanone
-
pH 6.5, temperature not specified in the publication
0.0305
2-(4-chlorobenzylidene)cyclopentyl ethyl ether
-
pH 6.5, temperature not specified in the publication
0.0000007
3',3'',5',5''-tetrabromophenolphthalein
-
binding to NADPH-enzyme complex via ordered bi-bi-mechanism
0.000009
3,5-dibromosalicylic acid
-
-
0.0000059 - 0.0028
3,5-dichlorosalicylic acid
0.000009
3,5-diiodosalicylic acid
-
-
0.000004 - 0.000113
3-bromo-5-phenylsalicylic acid
0.00000085 - 0.00007
3-chloro-5-phenylsalicylic acid
0.00014
3-phenyl-5-bromosalicylic acid
-
-
0.0485
3-phenylcyclopentanecarboxylic acid
-
pH 6.5, temperature not specified in the publication
0.0000021
4'-butyl-5-chloro-4-hydroxybiphenyl-3-carboxylic acid
-
wild-type, 25C, pH not specified in the publication
2.84
5'-adenylic acid
-
pH 7.8, 23C
0.0000013
5-chloro-4-hydroxy-3'-methylbiphenyl-3-carboxylic acid
-
wild-type, 25C, pH not specified in the publication
0.0000026
5-chloro-4-hydroxy-4'-methylbiphenyl-3-carboxylic acid
-
wild-type, 25C, pH not specified in the publication
0.00000086
5-chloro-4-hydroxybiphenyl-3-carboxylic acid
-
wild-type, 25C, pH not specified in the publication
0.0000013
5-fluoro-4-hydroxybiphenyl-3-carboxylic acid
-
wild-type, 25C, pH not specified in the publication
0.021
Acetylsalicylate
-
-
0.00087
adenosine 2'-monophospho- 5'-diphosphoribose
-
pH 7.8, 23C
0.95
adenosine diphosphoribose
-
pH 7.8, 23C
0.34
ADP
-
pH 7.8, 23C
0.01
aminopyridine 1,N6-ethenoadenine dinucleotide phosphate
-
pH 7.8, 23C
0.0029
aminopyridine adenine dinucleotide phosphate
-
pH 7.8, 23C
0.022
Diazotized 3-aminopyridine 1,N6-ethenoadenine dinucleotide phosphate
-
pH 7.8, 23C
0.0005
Diazotized 3-aminopyridine adenine dinucleotide phosphate
-
pH 7.8, 23C
9.29
N-1-butylnicotinamide chloride
-
pH 7.8, 23C
1.24
N-1-decylnicotinamide chloride
-
pH 7.8, 23C
8.95
N-1-ethylnicotinamide chloride
-
pH 7.8, 23C
3.39
N-1-heptylnicotinamide chloride
-
pH 7.8, 23C
6.59
N-1-hexylnicotinamide chloride
-
pH 7.8, 23C
0.205 - 14.8
N-1-methylnicotinamide chloride
3.29
N-1-nonylnicotinamide chloride
-
pH 7.8, 23C
4.01
N-1-octylnicotinamide chloride
-
pH 7.8, 23C
9.35
N-1-pentylnicotinamide chloride
-
pH 7.8, 23C
8.24
N-1-propylnicotinamide chloride
-
pH 7.8, 23C
0.487
N-1-undecylnicotinamide chloride
-
pH 7.8, 23C
0.00074
NADP+
-
pH 7.8, 23C
0.0078
salicylate
-
-
additional information
additional information
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0729
1-phenylcyclopentanecarboxylic acid
Homo sapiens
-
pH 6.5, temperature not specified in the publication
0.035
2-(4-chlorobenzylidene)cyclopentanone
Homo sapiens
-
pH 6.5, temperature not specified in the publication
0.0621
2-(4-chlorobenzylidene)cyclopentyl ethyl ether
Homo sapiens
-
pH 6.5, temperature not specified in the publication
0.0986
3-phenylcyclopentanecarboxylic acid
Homo sapiens
-
pH 6.5, temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.002
-
reduction of 0.06 mM prostaglandin E2
0.007
-
reduction of 0.03 mM 17alpha-hydroxy-pregnenolone
0.012
-
+/-0.005
0.013
-
reduction of 100 mM D-glucose
0.016
-
reduction of 0.03 mM prednisolone
0.017
-
reduction of 100 mM D-galactose
0.024
-
+/-0.006
0.025
-
reduction of 0.03 mM prednisone
0.038 - 0.046
-
calculated from 17beta-estadiol dehydrogenase activity
0.067
-
reduction of 0.05 mM pregnenolone
0.081
-
-
0.115
-
-
0.2596
-
insect cells
0.2769
-
HSD2, reduction of 17alpha-hydroxyprogesterone
0.282
-
measured with cortisone
0.332
-
+/-0.047, Escherichia coli
0.9
-
reduction of 0.06 mM 5alpha-pregnane-3,20-dione
1.3
-
pH 6.5, temperature not specified in the publication
1.462
-
HSD1, reduction of 17alpha-hydroxyprogesterone
2.09
-
20alpha-hydroxyprogesterone
2.5
-
oxidation of 0.06 mM 20alpha-hydroxy-5beta-pregnan-3-one
3.815
-
HSD2, reduction of progesterone
4.618
-
HSD1
6.515
-
HSD2
8.154
-
HSD1, reduction of progesterone
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 7.5
-
NADPH
5.6
-
steroid reduction
6 - 6.5
-
steroid reduction e.g. 20alpha-dihydrocortisol with MES, MOPS or sodium phosphate, NADH
6
-
renal NADH-dependent 20alpha-hydroxysteroid dehydrogenase
6 - 6.5
-
17alpha-hydroxyprogesterone reduction
6.5
-
hepatic NADPH-dependent 20alpha-hydroxysteroid dehydrogenase
6.8 - 7.2
-
NADH
7.7
-
assay at
7.8 - 8.2
-
-
10.5
-
steroid oxidation
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4 - 10
-
-
5.4 - 7.6
-
steroid reduction e.g. 20alpha-dihydrocortisol with MES, MOPS or sodium phosphate, NADH
5.8 - 10.5
-
25C, below and above range inactivation
6.3 - 9
-
steroid oxidation e.g. cortisol with Tris hydrochloride, NAD+
6.5 - 9
-
pH 6.8 favouring progesterone to 20alpha-hydroxyprogesterone reaction and pH 8.0 vice versa
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
23
-
assay at
25
-
assay at
50
-
reduction of 17alpha-hydroxyprogesterone
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0 - 55
-
10% of maximal reaction rate at 0C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
abdominal subcutaneous and omental adipose tissue, the enzyme activity is highest in women with visceral obesity, expression analysis
Manually annotated by BRENDA team
-
high expression level
Manually annotated by BRENDA team
-
breast cancer cells: tumorgenic strains MCF-7, MDA-MB-231, T-47D, nontumorgenic strain MCF-10A
Manually annotated by BRENDA team
placental cytotrophoblast villus
Manually annotated by BRENDA team
-
fetal
Manually annotated by BRENDA team
-
20alpha-HSD mRNA highly expressed
Manually annotated by BRENDA team
endometrial glandular epithelial cell
Manually annotated by BRENDA team
moderate expression rate of AKR1C23
Manually annotated by BRENDA team
preovulatory, very high expression rate, expression analysis of AKR1C23, activity during follicular luteinization, overview
Manually annotated by BRENDA team
-
20alpha-HSD mRNA lower expressed
Manually annotated by BRENDA team
moderate expression rate of AKR1C23
Manually annotated by BRENDA team
very low expression rate of AKR1C23
Manually annotated by BRENDA team
low expression rate of AKR1C23
Manually annotated by BRENDA team
placental cytotrophoblast villus
Manually annotated by BRENDA team
additional information
-
unfixed tissue section, soluble, retention by PVA
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
amniotic fluid
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
34000
-
gel filtration
38000
-
1 * 38000, SDS-PAGE
41000
-
gel filtration, non-reducing conditions
48150
-
estimated by 1.3 kb cDNA
75100
-
thin layer gel filtration
160000
-
+/-2000 SDS-PAGE, PAGE, gel filtration-HPLC
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
tetramer
-
4 * 40000, identical, SDS-PAGE, N-terminal amino acid sequence
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
phosphoprotein
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystal structure of AKR1C1 complexed with the first structure-based designed inhibitor 3-chloro-5-phenylsalicylic acid bound in the active site is reported. The binding of 3-chloro-5-phenylsalicylic acid to AKR1C1 results in a conformational change in the side chain of Phe311 to accommodate the bulky phenyl ring substituent at the 5-position of the inhibitor
-
docking model with substrates 5alpha-pregnane-3alpha,20alpha-diol and 5beta-pregnan-3alpha-ol-20-one. In the docked model of 5alpha-pregnane-3alpha,20alpha-diol the conformation of the steroid molecule is similar to that of 20alpha-hydroxyprogesterone in the crystal structure of the AKR1C1 complex where the steroid does not interact with the catalytic residues Tyr55 and His117. In the case of 5beta-pregnan-3alpha-ol-20-one the steroid interacts with the catalytic residue His117 and forms close contacts with Leu308
-
in complex with NADP+ and progesterone; purified recombinant enzyme in complex with cofactor and several substrates, hanging drop vapour diffusion method, 4C, HEPES or sodium acetate buffer, CaCl2, precipitant is PEG 4000, X-ray diffraction structure determination and analysis at 2.4-2.5 A resolution
-
in ternary complex with NADP+ and 3,5-dichlorosalicylic acid, hanging drop vapour diffusion method, using 25% (v/v) polyethylene glycol monomethyl ether 550, 0.02 M zinc sulfate in 0.1 M MES buffer (pH 6.5)
-
mutant L308V in complex with the inhibitor 3,5-dichlorosalicylic acid, to 1.9 A resolution. The inhibitor molecule is anchored from its carboxylate group that forms hydrogen bonds with the catalytic residues His117 and Tyr55, while the hydroxyl group is hydrogen bonded to His222. Van der Waals contacts are present between the inhibitor and residues Leu54, Leu306, and Phe311. Unlike the WT enzyme, the side-chain of the mutated Val308 makes long contacts with the inhibitor, the closest point of contact being 3.9 A
-
ternary complex with NADP+ and 20alpha-hydroxyprogesterone
-
in complex with NADP+ and progesterone, with NADP+ and dihydrotestosterone, with NADP+ and 4-androstenedione; purified recombinant enzyme in complex with cofactor and several substrates, hanging drop vapour diffusion method, 4C, HEPES or sodium acetate buffer, CaCl2, precipitant is PEG 4000, X-ray diffraction structure determination and analysis at 1.7-1.9 A resolution
-
isozyme HSD1, HSD2
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.2
-
activity destroyed below
285988
4.5 - 11.5
-
25C, below and above range total loss of activity
285998
5.5
-
at pH 5.5 for 30 min, after first purification step
285988
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
38
-
half-life 7.6 min
40
-
up to, for 5 min 95% initial activity, rapidly inactivated above 45C
45
-
rapidly inactivated above
55
-
rapidly inactivated
60
-
10 min, pH 5.5, complete inactivation of activity of purification step 1 and 2
95
-
15 min, almost total loss of activity
additional information
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
2-mercaptoethanol for stabilization during purification
-
20%, v/v, glycerol for stabilization during purification
-
glycerol for prevention of large activity loss
-
NADP+ protects against thermal denaturation, steroid substrate does not
-
NADP+ protects against thermal inactivation, 20alpha-hydroxyprogesterone does not
-
significant activity loss by repeated thawing and freezing
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-15C, 0.005 mg/ml, 0.01 M potassium phosphate buffer, pH 8.0, 50% propylene glycol, 0.2 M KCl, 2 months
-
-20C, porcine testes, 0.1 M phosphate buffer, pH 7.00.1 M phosphate buffer, pH 7.0, several months
-
-20C, purified enzyme, 10 mM Tris/HCl, pH 7.5, 0.5 mM EDTA, 1 mM 2-mercaptoethanol, 20%, v/v, glycerol, 2 weeks, little activity loss
-
-70C, 2.8 mg/ml protein concentration, 20 mM potassium phosphate buffer, pH 7.0, 1 mM EDTA, 1 mM beta-mercaptoethanol, 30%, v/v, glycerol
-
-80C, particulate and cytosolic fraction after homogenization
-
4 or -20C, 2 mg/ml purified protein, 0.1 M phosphate buffer, pH 6-9, several days or for months
-
4C or -20C, above 0.5 mg of purified protein per ml, 50 mM phosphate buffer, pH 6.8, 10 mM 2-mercaptoethanol, 50% glycerol, v/v, several days
-
4C or -20C, ammonium sulfate fraction of purification step 2, over night or several months
-
4C, cytosol preparation prior to purification, several months
-
4C, in presence of glycerol and DTT
-
4C, Sephadex G-100 fraction, rapid decrease, 2 days, 50% activity loss, 80% activity remaining by addition of 20%, v/v, glycerol
-
glycerol
-
no activity after single freeze-thaw of enzyme at any stage
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
affinity binding to glutathione-Sepharose and thrombin digestion of bacterial lysate, ion exchange and affinity chromatography of enzyme produced by insect cells
-
ammonium sulfate precipitation, affinity chromatography
-
ammonium sulfate precipitation, affinity chromatography, gel filtration
-
ammonium sulfate precipitation, chromatography
-
ammonium sulfate precipitation, ultrafiltration, chromatography
-
anion exchange and affinity chromatography
-
anion exchange and affinity chromatography, gel filtration, HPLC
-
co-purification with 17beta-estradiol dehydrogenase, EC 1.1.1.62, affinity chromatography
-
co-purification with aldehyde reductase and dihydrodiol dehydrogenase
-
column chromatography, gel filtration
-
five steps co-purification with aldehyde reductase and dihydrodiol dehydrogenase, ammonium sulfate precipitation, HPLC
-
gel filtration, affinity chromatography
-
ion exchange chromatography
-
isozyme HSD1 and HSD2, anion-exchange and affinity chromatography, capillary electrophoresis