Information on EC 1.14.14.16 - steroid 21-monooxygenase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
1.14.14.16
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RECOMMENDED NAME
GeneOntology No.
steroid 21-monooxygenase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
a C21 steroid + [reduced NADPH-hemoprotein reductase] + O2 = a 21-hydroxy-C21-steroid + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydroxylation
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-
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oxidation
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redox reaction
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-
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reduction
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Metabolic pathways
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Steroid hormone biosynthesis
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androgen and estrogen metabolism
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SYSTEMATIC NAME
IUBMB Comments
steroid,NADPH-hemoprotein reductase:oxygen oxidoreductase (21-hydroxylating)
A P-450 heme-thiolate protein responsible for the conversion of progesterone and 17alpha-hydroxyprogesterone to their respective 21-hydroxylated derivatives, 11-deoxycorticosterone and 11-deoxycortisol. Involved in the biosynthesis of the hormones aldosterone and cortisol. The electron donor is EC 1.6.2.4, NADPH---hemoprotein reductase.
CAS REGISTRY NUMBER
COMMENTARY hide
9029-68-9
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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-
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Manually annotated by BRENDA team
expression in human embryonic kidney 293 cells
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Manually annotated by BRENDA team
rainbow trout
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Manually annotated by BRENDA team
pig
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(+)-benzphetamine + NADH + O2
N-demethyl-benzphetamine + NAD+ + H2O
show the reaction diagram
-
-
-
?
11,17-dihydroxyprogesterone + NADH + O2
cortisol + NAD+ + H2O
show the reaction diagram
-
-
-
?
11beta-hydroxyprogesterone + NADH + O2
corticosterone + NAD+ + H2O
show the reaction diagram
-
-
-
?
17,17-dimethyl-18-norandrosta-1,4,13-trien-3-one + [reduced NADPH-hemoprotein reductase] + O2
16beta-hydroxy-17,17-dimethyl-18-norandrosta-1,4,13-trien-3-one + 16alpha-hydroxy-17,17-dimethyl-18-norandrosta-1,4,13-trien-3-one + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
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i.e. metandienone
product identification by GC-EI-MS analysis
-
?
17,17-dimethyl-18-norandrosta-1,4,13-trien-3-one + [reduced NADPH-hemoprotein reductase] + O2
20beta-hydroxy-17,17-dimethyl-18-norandrosta-1,4,13-trien-3-one + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
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i.e. metandienone
product identification by GC-EI-MS analysis
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?
17-fluoro-progesterone + [reduced NADPH-P450 reductase] + O2
17-fluoro-11-deoxycorticosterone + [oxidized NADPH-P450 reductase] + H2O
show the reaction diagram
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-
-
-
?
17-hydroxy-progesterone + NADH + O2
17-hydroxy-11-deoxy-corticosterone + NAD+ + H2O
show the reaction diagram
17-hydroxyprogesterone + NADPH + H+ + O2
11-deoxycortisol + NADP+ + H2O
show the reaction diagram
17-hydroxyprogesterone + NADPH + O2
corticosteroids + NADP+ + H2O
show the reaction diagram
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-
-
?
17-hydroxyprogesterone + [reduced NADPH-hemoprotein reductase] + O2
11-deoxycortisol + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
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-
-
-
?
17alpha-hydroxy-progesterone + NADH + O2
17alpha-hydroxy-11-deoxy-corticosterone + NAD+ + H2O
show the reaction diagram
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preferred substrate
-
-
?
17alpha-hydroxyprogesterone + AH2 + O2
11-deoxycortisol + A + H2O
show the reaction diagram
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-
-
-
?
17alpha-hydroxyprogesterone + NADH + O2
17,21-dihydroxyprogesterone + NAD+ + H2O
show the reaction diagram
17alpha-hydroxyprogesterone + NADPH + H+ + O2
11-deoxycortisol + NADP+ + H2O
show the reaction diagram
17alpha-hydroxyprogesterone + NADPH + O2
11-deoxycortisol + NADP+ + H2O
show the reaction diagram
17alpha-hydroxyprogesterone + NADPH + O2
17,21-dihydroxyprogesterone + NADP+ + H2O
show the reaction diagram
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-
-
?
17alpha-hydroxyprogesterone + [reduced NADPH-hemoprotein reductase] + O2
11-deoxycortisol + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
17alpha-hydroxyprogesterone + [reduced NADPH-P450 reductase] + O2
11-deoxycortisol + [oxidized NADPH-P450 reductase] + H2O
show the reaction diagram
a steroid + electron donor + O2
a 21-hydroxysteroid + oxidized electron donor + H2O
show the reaction diagram
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essential step in synthesis of steroid hormones by adrenal gland
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allopregnanolone + NADH + O2
21-hydroxy-allopregnanolone + NAD+ + H2O
show the reaction diagram
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isozyme CYP2D4, CYP2D6
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-
?
DELTA5-pregnen-3beta,17alpha-diol-20-one + NADH + O2
? + NAD+ + H2O
show the reaction diagram
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-
-
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DELTA5-pregnen-3beta-ol-20-one + NADH + O2
deoxycorticosterone + NAD+ + H2O
show the reaction diagram
progesterone + AH2 + O2
deoxycorticosterone + A + H2O
show the reaction diagram
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-
-
-
?
progesterone + NADH + O2
11-deoxycorticosterone + NAD+ + H2O
show the reaction diagram
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-
-
-
?
progesterone + NADH + O2
deoxycorticosterone + NAD+ + H2O
show the reaction diagram
progesterone + NADPH + H+ + O2
11-deoxycorticosterone + NADP+ + H2O
show the reaction diagram
progesterone + NADPH + H+ + O2
deoxycorticosterone + NADP+ + H2O
show the reaction diagram
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-
-
-
?
progesterone + NADPH + O2
deoxycorticosterone + NADP+ + H2O
show the reaction diagram
progesterone + [reduced NADPH-hemoprotein reductase] + O2
11-deoxycorticosterone + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
progesterone + [reduced NADPH-hemoprotein reductase] + O2
16alpha-hydroxy-progesterone + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
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mutant V359A produces an additional metabolite, 16alpha-hydroxyprogesterone of progesterone, very low activity with the wild-type enzyme
product identification by TLC
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?
progesterone + [reduced NADPH-hemoprotein reductase] + O2
16alpha-hydroxyprogesterone + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
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mutants V359A and V359G both produce an additional metabolite, 16alpha-hydroxyprogesterone
product identification by TLC
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?
progesterone + [reduced NADPH-P450 reductase] + O2
11-deoxycorticosterone + [oxidized NADPH-P450 reductase] + H2O
show the reaction diagram
additional information
?
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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
17-hydroxyprogesterone + NADPH + H+ + O2
11-deoxycortisol + NADP+ + H2O
show the reaction diagram
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-
-
-
?
17-hydroxyprogesterone + NADPH + O2
corticosteroids + NADP+ + H2O
show the reaction diagram
-
-
-
?
17-hydroxyprogesterone + [reduced NADPH-hemoprotein reductase] + O2
11-deoxycortisol + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
-
-
-
-
?
17alpha-hydroxyprogesterone + [reduced NADPH-hemoprotein reductase] + O2
11-deoxycortisol + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
17alpha-hydroxyprogesterone + [reduced NADPH-P450 reductase] + O2
11-deoxycortisol + [oxidized NADPH-P450 reductase] + H2O
show the reaction diagram
a steroid + electron donor + O2
a 21-hydroxysteroid + oxidized electron donor + H2O
show the reaction diagram
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essential step in synthesis of steroid hormones by adrenal gland
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progesterone + NADPH + H+ + O2
11-deoxycorticosterone + NADP+ + H2O
show the reaction diagram
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?
progesterone + [reduced NADPH-hemoprotein reductase] + O2
11-deoxycorticosterone + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
progesterone + [reduced NADPH-P450 reductase] + O2
11-deoxycorticosterone + [oxidized NADPH-P450 reductase] + H2O
show the reaction diagram
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cytochrome P450
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cytochrome P450S21
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steroid 21-hydroxylase system consists of cytochrome P-450S21, NADPH-cytochrome P-450 reductase (EC 1.6.2.4) and steroid 21-monooxygenase (EC 1.14.99.10)
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NADPH
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
17alpha-hydroxyprogesterone
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inhibits above 0.2mM
antibody to cytochrome P-450BPA
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antibody to NADPH-cytochrome P-450 reductase
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antimycin A
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15% inhibition at 1mg per l
ascorbate
azide
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9% inhibition at 1 mM
carbon monoxide
CuSO4
cyanide
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14% inhibition at 1 mM
cytochrome c
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complete inhibition at 0.1 mM, 0.003 mM
diethylaminoethyldiphenylpropylacetic acid SKF 525 A
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9% inhibition at 1 mM
fluoxetine
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50% inhibition at 0.002 mM, substrate allopregnanolone
HgCl2
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complete inhibition at 0.1 mM
ketoconazole
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inhibits hydroxylation activity with progesterone and 17-fluoroprogesterone to the same amount
p-chloromercuribenzoate
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complete inhibition at 1 mM, but not inhibitory at 0.1 mM
Phenylisocyanide
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inhibition at 0.5 mM
progesterone
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quinidine
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resveratrol
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decreases adrenal enzyme expression in vivo and in cell culture. Corticosterone production is inhibited 47% by 0.05 mM resveratrol in vitro and 20% ex vivo, while progesterone production is elevated to 400% of control in vitro
RU38486
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sodium o-(3-hydroxymercuri-2-methoxypropyl)carbamyl-phenoxyacetc acid (mersalyl)
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complete inhibition at 1 mM
additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-mercaptoethanol
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bovine serum albumin
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Cymal 5
optimal concentration is 0.002%, decrease in activity above 0.05%
dithiothreitol
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EDTA
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Emulgen 911
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Emulgen 913
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maximum with 0.008% v/v
GSH
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GSSG
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L-cysteine
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L-cystine
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lysophosphatidylcholine
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sodium cholate
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Sodium deoxycholate
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Triton X-100
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2.3 - 9.2
17-hydroxy-progesterone
0.0038 - 0.031
17-hydroxyprogesterone
0.00044 - 0.0108
17alpha-hydroxyprogesterone
0.00021 - 9.2
progesterone
additional information
additional information
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.322
17a-hydroxyprogesterone
Bos taurus
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0.22 - 4
17alpha-hydroxyprogesterone
0.078 - 2.8
progesterone
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1567 - 2667
17alpha-hydroxyprogesterone
1170
1517 - 13330
progesterone
286
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00027
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37C, mutant P482S, substrate 17-hydroxy-progesterone
0.00038
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37C, mutant P482S, substrate progesterone
0.00117
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37C, wild-type, substrate progesterone
0.00122
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37C, wild-type, substrate 17-hydroxy-progesterone
0.00129
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37C, mutant A15T, substrate 17-hydroxy-progesterone
0.00148
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37C, mutant A15T, substrate progesterone
0.003
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21-hydroxylation of progesterone at 26C
0.0038
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21-hydroxylation of 17alpha-hydroxyprogesterone at 26C
0.0052
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N-demethylation of (+)-benzphetamine
0.0077
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21-hydroxylation of progesterone
0.0144
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21-hydroxylation of progesterone
0.0195
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cytochrome P-450-linked mixed function oxidase system from adrenal gland, 21-hydroxylation of 17alpha-hydroxyprogesterone
0.0452
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21-hydroxylation of 17alpha-hydroxyprogesterone
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 7
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7.2
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assay at
7.5
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assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 8
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about 50% of activity maximum at pH 5.5 and 8.0
7.5 - 8.5
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
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assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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cultured cell
Manually annotated by BRENDA team
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anterior qurter of head kidney
Manually annotated by BRENDA team
additional information
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no activity in: gill, heart, liver, intestine, kidney, immature gonad, skeletal muscle
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
12400
gel filtration in presence of 0.12% Cymal 5, protein elutes as monomer surrounded by a micelle of detergent
47000
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SDS-PAGE
47500
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SDS-PAGE
48870
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calculation form amino acid composition
50000
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x * 50000, SDS-PAGE
52000
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SDS-PAGE
53000
1 * 53000, calculated
80700
gel filtration in presence of 1% cholate, protein elutes as monomer surrounded by a micelle of cholate
167000
gel filtration in presence of 0.056% Cymal 6, protein elutes as monomer surrounded by a micelle of detergent
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
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x * 50000, SDS-PAGE
monomer
1 * 53000, calculated
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
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3.6% carbohydrate
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
purified recombinant His-tagged CYP21A2 mutant T241R/L442A in complex with substrate 17-hydroxyprogesterone, hanging drop vapor diffusion method, 0.2 mM protein in 50 mM potassium phosphate, pH 7.4, 20% glycerol, 0.1 mM DTT, 0.1 mM EDTA, 0.25% Cymal 5, and 50 mM NaCl, is mixed with 0.4 mM, containing 2% v/v C2H5OH, and 5-15% w/v PEG 3350, 0.5 M ammonium sulfate, and 0.1 M HEPES, pH 7.0, 20C, few days, X-ray diffraction structure determination and analysis at 3.0 A resolution
in complex with progesterone, sitting drop vapor diffusion method, using 0.1 M sodium HEPES (pH 7.5) containing 0.2 M ammonium sulfate and 25% (w/v) polyethylene glycol 3350
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70C, 0.2 M potassium phospate, pH 7.4, 20% glycerol, 0.1 mM EDTA, 3 months without loss of activity
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0C, 50 mM Tris, pH 7.2, 20% glycerol, 0.15% emulgen, 0.1 mM dithiothreitol, 0.1 mM EDTA, several weeks spectroscopically stable
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25C, 50 mM Tris, pH 7.2, 20% glycerol, 0.15% emulgen, 0.1 mM dithiothreitol, 0.1 mM EDTA, several hours spectroscopically stable, without Emulgen 50% precipitation after 30 min
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
enzyme system consisting of cytochrome P-450S21 and NADPH-cytochrome P-450 reductase
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HisTrap HP column chromatography (using Ni2+ ions immobilized onto a metal-chelating column)
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Ni-NTA agarose column chromatography, and SP Fast-Flow Sepharose column chromatography
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recombinant His-tagged enzyme from Escherichia coli strain JM109 by nickel affinity chromatography
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recombinant His-tagged wild-type enzyme and mutants from Escherichia coli by nickel affinity and anion exchange chromatography, followed by gel filtration
recombinant wild-type and mutant enzymes from yeast microsomes
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in COS-1 cells
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expressed in Escherichia coli
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expressed in Escherichia coli BL21-Gold DE(3) cells
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expressed in Sf9 insect cell microsomes
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expressed in Spodoptera frugiperda insect cell microsomes using a baculovirus expression system
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expression of His-tagged enzyme in Escherichia coli strain JM109, coexpression with molecular chaperones GroES and GroEL
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expression of wild-type and mutant enzymes in yeast microsomes
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gene CYP11B!, DNA and amino acid sequence determination and analysis, genotyping
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gene CYP21, expression in Schizosaccharomyces pombe strain CAD18, method optimization and evaluation, and quantification of the intracellular redox cofactor pool in transformed cells, overview
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gene CYP21A2 or C3B21RA, DNA and amino acid sequence determination and analysis, recombinant expression of His-tagged wild-type enzyme and mutants in Escherichia coli
gene CYP21A2, DNA and amino acid sequence determination and analysis, genotyping. Recombinant expression of mutant H365Y/R356W in HEK-293T cells; gene CYP21A2, genotyping, expression of wild-type and mutant enzymes in HEK-293T and hepatoblastoma C3A cells, the H365Y enzyme is produced in more variable amounts than wild-type CYP21A2
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mutant enzymes are expressed in COS-7 cells
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mutant enzymes are expressed in Saccharomyces cerevisiae strain W303B
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recombinant expression in yeast microsomes
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
T241R
site-directed mutagenesis, the mutant shows improved solubility properties compared to the wild-type enzyme
T241R/L442A
site-directed mutagenesis, the mutant shows greatly improved solubility properties compared to the wild-type enzyme
A15T
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natural mutation found in patients with classical congenital adrenal hyperplasia, no significant difference in activity compared to wild-type
A265C
naturally occuring mutation, the mutation causes side-chain steric clashes with the neighboring residues
A391T
naturally occuring mutation, the mutation disrupts the hydrophobicity of the region
A434V
naturally occuring mutation, the mutation causes steric clashes with the heme rendering the enzyme almost inactive
C169R
naturally occuring mutation, the mutation alters the region's hydrophobicity, conserved residue C169 makes hydrophobic interactions with the loop between E-F helices and F-helix
D407N
naturally occuring mutation, the mutation prevents salt bridge formation resulting in a localized, as opposed to global, destabilization of tertiary structure
E320K
naturally occuring mutation, the mutation of E320, which is a highly conserved residue on a negatively charged Glu-Glu-Leu-Asp (EELD) motif, alters the charge on the motif
E351K
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rare missense mutation located in the ERR triad and found in a patient with virilizing congenital hyperplasia. Residual activity is about 1% of wild-type for both 17-hydroxyprogesterone and progesterone
E431K
naturally occuring mutation, the mutation prevents salt bridge formation resulting in a localized, as opposed to global, destabilization of tertiary structure
F404S
naturally occuring mutation, the mutation prevents stable packing interactions resulting in salt-wasting congenital adrenal hyperplasia
G178A
naturally occuring mutation, the mutation causes reduced structural flexibility of the sharp fold between the E- and F-helices
G291C
naturally occuring mutation, the mutation abolishes substrate binding causing salt-wasting congenital adrenal hyperplasia
G291R
naturally occuring mutation, the mutation abolishes substrate binding causing salt-wasting congenital adrenal hyperplasia
G291S
naturally occuring mutation, the mutation abolishes substrate binding causing salt-wasting congenital adrenal hyperplasia
G292D
naturally occuring mutation, the mutation abolishes substrate binding causing salt-wasting congenital adrenal hyperplasia
G424S
naturally occuring mutation, the mutation imparts rigidity to the loop between K'- and L-helix
G56R
naturally occuring mutation, P57 and G56 form the hinge between the membrane interacting N-terminus and rest of the protein. The substitution of G56 with a polar and rigid Arg residue disrupts the hinge affecting the interactions of CYP21A2 with the membrane
G90V
naturally occuring mutation, mutation of G90 to valine affects the ability of R91 to hydrogen bond with heme, causing salt-wasting congenital adrenal hyperplasia
H119R
naturally occuring mutation, the mutation causes side-chain steric clashes with the neighboring residues
H365W
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the naturally occuring CYP21A2 mutant exhibits minimal 21-hydroxylase activity to convert 17-hydroxyprogesterone to 11-deoxycortisol or progesterone to 11-deoxycorticosterone compared to the wild-type
H365Y/R356W
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a naturally occuring 21-hydroxylase mutation in the CYP21A2 gene, that is involved in congenital adrenal hyperplasia, an autosomal recessive disorder, phenotype, overview. The H365Y enzyme is produced in more variable amounts than wild type; heterozygote H365Y/R356W individuum for two CYP21A2 gene mutations each inherited from a different parent
H62L
naturally occuring mutation, the mutation may disrupt hydrogen bonding to reduce, but not eliminate, enzyme activity
I171N
-
mutation identified in Italian patient with congenital adrenal hyperplasia, less than 1% of wild-type enzyme activity
I194N
naturally occuring mutation, the mutation causes side-chain steric clashes with the neighboring residues
I230T
naturally occuring mutation, the mutation causes side-chain steric clashes with the neighboring residues
I236N/V237E/M239K
-
naturally occuring mutant, no enzymic activity, dominant negative effect over wild-type with 35% decrease in activity
I471A
-
site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme
I471G
-
site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme
I77T
naturally occuring mutation, the mutation disrupts the hydrophobic environment
K121Q
naturally occuring mutation, the mutation impairs the interaction with the P450 oxidoreductase
K122Q
-
missense mutation causing nonclassical 21-hydroxylase deficiency, shows reduced activity of 14% for the conversion of 17alpha-hydroxyprogesterone and 19% for the conversion of progesterone compared to wild type
L107R
naturally occuring mutation, the mutation abolishes heme binding and causes salt-wasting congenital adrenal hyperplasia
L107X
-
site-directed mutagenesis, inactive mutant
L109X
-
site-directed mutagenesis, inactive mutant
L142P
naturally occuring mutation, the mutation of the D-helix causes helical disruption and destabilization of secondary structures
L166P
naturally occuring mutation, the mutation of the E-helix causes helical disruption and destabilization of secondary structures
L167P
naturally occuring mutation, the mutation of the E-helix causes helical disruption and destabilization of secondary structures
L236N/V237E/M239K
-
the mutation is associated with congenital adrenal hyperplasia
L261P
naturally occuring mutation, the mutation of the H-helix causes helical disruption and destabilization of secondary structures
L300F
naturally occuring mutation, the mutation causes localized destabilization of secondary structure
L307M
naturally occuring mutation, the mutation disrupts the optimal packing of side chains but does not alter the hydrophobic environment
L307V
naturally occuring mutation, the mutation disrupts the optimal packing of side chains but does not alter the hydrophobic environment
L308F
naturally occuring mutation, the mutation causes localized destabilization of secondary structure
L353R
naturally occuring mutation, the mutation abolishes heme binding and causes salt-wasting congenital adrenal hyperplasia
L363W
naturally occuring mutation, the mutation causes steric clashes with the heme rendering the enzyme almost inactive
N387K
naturally occuring mutation, the mutation causes side-chain steric clashes with the neighboring residues
P30E
naturally occuring mutation causing disruption of the interaction between the carbon of P30 in the N-terminal loop and the side chain of Y376 within the beta5-beta6 hairpin loop resuting in the salt-wasting disease
P432L
naturally occuring mutation, the mutation makes the structure more flexible and prevents cysteine from being presented to heme
P459H
naturally occuring mutation, the mutation disrupts the hydrophobicity of the region
P463L
naturally occuring mutation, the mutation interferes with the conformation of the beta8-beta9 loop with the subsequent closure of substrate entrance channel
P482S
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natural mutation found in patients with nonclassical congenital adrenal hyperplasia, precocious pubarche, menstrual irregularities or hypertrichosis, about 70% of activity compared to wild-type
Q318X
-
the mutation is associated with congenital adrenal hyperplasia
Q481P
naturally occuring mutation, the mutation destabilizes the structure rendering the protein inactive
R124H
naturally occuring mutation, the mutation causes side-chain steric clashes with the neighboring residues
R132C
naturally occuring mutation, the mutation impairs the interaction with the P450 oxidoreductase
R149C
naturally occuring mutation, the mutation prevents salt bridge formation resulting in a localized, as opposed to global, destabilization of tertiary structure
R233G
naturally occuring mutation, the mutation may prevent R233 from binding to the 3-keto oxygen of the proximal 17OHP in the proper orientation, it does not influence protein activity significantly, resulting in minimal phenotype
R233K
naturally occuring mutation, the mutation may prevent R233 from binding to the 3-keto oxygen of the proximal 17OHP in the proper orientation, it does not influence protein activity significantly, resulting in minimal phenotype
R339H
naturally occuring mutation, the mutation impairs the interaction with the P450 oxidoreductase
R341W
naturally occuring mutation, the mutation impairs the interaction with the P450 oxidoreductase
R356P
naturally occuring mutation, the mutation disrupts the interaction of R356 with Q389 rendering the enzyme inactive and causing salt-wasting congenital adrenal hyperplasia
R369Q
naturally occuring mutation, the mutation impairs the interaction with the P450 oxidoreductase
R408C/L
naturally occuring mutation, the mutation destabilizes structural elements because of the extensive loss of hydrogen bonds
R408H
naturally occuring mutation, the mutation prevents normal hydrogen bonding with E351 and R354
R426C
naturally occuring mutation, the mutation disrupts the interaction of residues R91 and R426 rendering the protein nonfunctional and causing salt-wasting congenital adrenal hyperplasia
R426H
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mutation identified in Italian patient with congenital adrenal hyperplasia, less than 1% of wild-type enzyme activity
R435C
naturally occuring mutation, the mutation prevents salt bridge formation resulting in a localized, as opposed to global, destabilization of tertiary structure
R479L
naturally occuring mutation, the mutation prevents salt bridge formation resulting in a localized, as opposed to global, destabilization of tertiary structure
R483P
naturally occuring mutation, the mutation prevents salt bridge formation resulting in a localized, as opposed to global, destabilization of tertiary structure
S301Y
naturally occuring mutation, the mutation causes side-chain steric clashes with the neighboring residues
T168N
naturally occuring mutation, the mutation causes side-chain steric clashes with the neighboring residues
T295X
naturally occuring mutation, the mutation abolishes substrate binding and causes salt-wasting congenital adrenal hyperplasia
T450P
naturally occuring mutation, the mutation reduces flexibility of beta8-sheet, which helps stabilize the very long C-terminal loop
V139E
naturally occuring mutation, mutation to glutamate disrupts the interaction with residues V440 and L436 on the L-helix causing instability of the enzyme, charge repulsions between the side chain of mutated V139E and E437 of the E-helix render the protein unstable and inactive causing salt-wasting congenital adrenal hyperplasia
V249A
naturally occuring mutation, the mutation causes side-chain steric clashes with the neighboring residues
V281G
naturally occuring mutation, the mutation causes a loss of the hydrophobic pocket
V304M
naturally occuring mutation, the mutation causes side-chain steric clashes with the neighboring residues
V359G
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site-directed mutagenesis, the mutant shows 10% reduced activity compared to the wild-type enzyme
V470A
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site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme
V470A/I471A
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site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme
V470G
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site-directed mutagenesis, the mutant shows activity similar to the wild-type enzyme
W302R
naturally occuring mutation, the mutation prevents stable packing interactions resulting in salt-wasting congenital adrenal hyperplasia
Y47C
naturally occuring mutation, the mutation disables hydrogen bonding with H38, the interaction is compensated by a weak His-Cys interaction
Y47L
naturally occuring mutation, the mutation disrupts hydrogen bonds and causes salt-wasting congenital adrenal hyperplasia
Y59N
naturally occuring mutation, the mutation disrupts the hydrophobicity of the region resulting in loss of function
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
biotechnology
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the CYP21 expression model system using resting Schizosaccharomyces pombe cells can be used for biotransformations
medicine