Information on EC 1.1.1.153 - sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)

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

EC NUMBER
COMMENTARY hide
1.1.1.153
-
RECOMMENDED NAME
GeneOntology No.
sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
L-erythro-7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH + H+
show the reaction diagram
L-erythro-tetrahydrobiopterin + 2 NADP+ = 6-pyruvoyl-5,6,7,8-tetrahydropterin + 2 NADPH + 2 H+
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Folate biosynthesis
-
-
Metabolic pathways
-
-
tetrahydrobiopterin biosynthesis I
-
-
SYSTEMATIC NAME
IUBMB Comments
L-erythro-7,8-dihydrobiopterin:NADP+ oxidoreductase
This enzyme catalyses the final step in the de novo synthesis of tetrahydrobiopterin from GTP. The enzyme, which is found in higher animals and some fungi and bacteria, produces the erythro form of tetrahydrobiopterin. cf. EC 1.1.1.325, sepiapterin reductase (L-threo-7,8-dihydrobiopterin forming).
CAS REGISTRY NUMBER
COMMENTARY hide
9059-48-7
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
low activity
-
-
Manually annotated by BRENDA team
; complete ORF
SwissProt
Manually annotated by BRENDA team
strain Oregon R
-
-
Manually annotated by BRENDA team
Drosophila melanogaster Oregon R
strain Oregon R
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
low activity
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Phycomyces sp.
-
-
-
Manually annotated by BRENDA team
Donryu
-
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
Sprague-Dawley
-
-
Manually annotated by BRENDA team
low activity
-
-
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1'-hydroxy-2'-oxopropyltetrahydropterin + NADP+
L-erythro-tetrahydrobiopterin + NADPH
show the reaction diagram
-
-
-
-
1'-hydroxy-2'-oxopropyltetrahydropterin + NADPH
L-erythrotetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
?
1'-oxo-2'-D-hydroxypropyl-tetrahydropterin + NADP+
D-sepiapterin + NADPH
show the reaction diagram
1'-oxo-2'-D-hydroxypropyl-tetrahydropterin + NADPH
tetrahydrodictyopterin + NADP+
show the reaction diagram
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
L-sepiapterin + NADPH
show the reaction diagram
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADPH
L-erythro-tetrahydrobiopterin + NADP+
show the reaction diagram
1,2-cyclohexadione + NADPH
?
show the reaction diagram
-
-
-
-
?
1,2-naphthoquinone + NADPH
?
show the reaction diagram
-
-
-
-
?
1,4-naphthoquinone + NADPH
?
show the reaction diagram
-
-
-
-
?
1-phenyl-1,2-propanedione + NADPH
?
show the reaction diagram
-
-
-
-
?
2,3-butanediol + NADP+
?
show the reaction diagram
-
-
-
-
?
2,3-dimethoxynaphthalene-1,4-dione + NADPH
?
show the reaction diagram
-
-
-
-
?
2,4-pentanedione + NADPH
?
show the reaction diagram
-
-
-
-
?
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
6-pyruvoyl tetrahydropterin + NADPH
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
show the reaction diagram
6-pyruvoyl tetrahydropterin + NADPH
L-threo-(6R,1'S,2'S)-5,6,7,8-tetrahydrobiopterin + NADP+
show the reaction diagram
6-pyruvoyl tetrahydropterin + NADPH + H+
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
show the reaction diagram
6-pyruvoyl tetrahydropterin + NADPH + H+
L-threo-(6R,1'S,2'S)-5,6,7,8-tetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
-
6-pyruvoyl tetrahydropterin + NADPH + H+
tetrahydrobiopterin + NADP+
show the reaction diagram
6-pyruvoyl-5,6,7,8-tetrahydropterin + NADPH
tetrahydrobiopterin + NADP+
show the reaction diagram
6-pyruvoyltetrahydropterin + 2 NADPH + 2 H+
L-erythro-tetrahydrobiopterin + 2 NADP+
show the reaction diagram
6-pyruvoyltetrahydropterin + 2 NADPH + 2 H+
L-threo-tetrahydrobiopterin + 2 NADP+
show the reaction diagram
6-pyruvoyltetrahydropterin + NADPH
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
show the reaction diagram
-
-
no synthesis of the D-isomer
-
?
9,10-phenanthrenequinone + NADP+
?
show the reaction diagram
-
-
-
-
?
9,10-phenanthrenequinone + NADPH
?
show the reaction diagram
-
-
-
-
?
acetohexamide + NADPH
?
show the reaction diagram
-
-
-
-
?
acetoin + NADPH
?
show the reaction diagram
acetophenone + NADPH
?
show the reaction diagram
-
-
-
-
?
benzil + NADPH
?
show the reaction diagram
benzylacetone + NADPH
?
show the reaction diagram
-
-
-
-
?
diacetyl + NADPH
?
show the reaction diagram
diacetyl + NADPH
acetoin + NADP+
show the reaction diagram
-
NADPH-dependent dicarbonyl reductase activity
-
-
?
dihydrotepidopterin + NADP+
?
show the reaction diagram
-
15% relative activity
-
-
?
isosepiapterin + NADPH
6-(1-hydroxypropyl)-dihydropterin + NADP+
show the reaction diagram
-
-
-
?
isosepiapterin + NADPH
? + NADP+
show the reaction diagram
-
-
-
-
r
L-erythro-dihydrobiopterin + NADP+
?
show the reaction diagram
-
-
-
-
?
L-erythro-dihydroneopterin + NADP+
?
show the reaction diagram
L-threo-dihydrobiopterin + NADP+
?
show the reaction diagram
-
D-isomer 45% relative activity
-
-
r
L-threo-dihydroneopterin + NADP+
?
show the reaction diagram
lactoyltetrahydropterin + NADPH
L-erythrotetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
?
lactoyltetrahydropterin + NADPH + H+
L-erythro-tetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
menadione + NADPH
?
show the reaction diagram
methylglyoxal + NADPH
?
show the reaction diagram
p-nitrobenzaldehyde + NADPH
p-nitrobenzyl alcohol + NADP+
show the reaction diagram
p-quinone + NADPH
?
show the reaction diagram
-
-
-
-
?
phenylglyoxal + NADPH
?
show the reaction diagram
phenylpropanedione + NADPH
phenylpropan-2,3-diol + NADP+
show the reaction diagram
-
NADPH-dependent dicarbonyl reductase activity
-
-
?
propiophenone + NADPH
?
show the reaction diagram
-
-
-
-
?
pyruvoyltetrahydropterin + NADPH
L-erythrotetrahydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
?
sepiapterin + NADPH
1'-hydroxy-2'-oxopropyltetrahydropterin + NADP+
show the reaction diagram
-
best substrate
-
-
?
sepiapterin + NADPH
7,8-dihydrobiopterin + NADP+
show the reaction diagram
-
-
-
-
?
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
xanthopterin B2 + NADPH
6-(1',2'-dihydroxypropyl)-dihydrolumazine + NADP+
show the reaction diagram
-
-
-
?
xanthopterin-B2 + NADPH
? + NADP+
show the reaction diagram
-
-
-
-
r
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
1'-oxo-2'-D-hydroxypropyl-tetrahydropterin + NADP+
D-sepiapterin + NADPH
show the reaction diagram
1'-oxo-2'-D-hydroxypropyl-tetrahydropterin + NADPH
tetrahydrodictyopterin + NADP+
show the reaction diagram
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
L-sepiapterin + NADPH
show the reaction diagram
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADPH
L-erythro-tetrahydrobiopterin + NADP+
show the reaction diagram
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
show the reaction diagram
6-pyruvoyl tetrahydropterin + NADPH
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
show the reaction diagram
-
-
-
-
?
6-pyruvoyl tetrahydropterin + NADPH
L-threo-(6R,1'S,2'S)-5,6,7,8-tetrahydrobiopterin + NADP+
show the reaction diagram
6-pyruvoyl tetrahydropterin + NADPH + H+
tetrahydrobiopterin + NADP+
show the reaction diagram
-
final step in the synthesis of tetrahydrobiopterin, role in detoxification of exogenous carbonyl compounds suggested
-
-
?
6-pyruvoyl-5,6,7,8-tetrahydropterin + NADPH
tetrahydrobiopterin + NADP+
show the reaction diagram
6-pyruvoyltetrahydropterin + 2 NADPH + 2 H+
L-threo-tetrahydrobiopterin + 2 NADP+
show the reaction diagram
6-pyruvoyltetrahydropterin + NADPH
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
show the reaction diagram
-
-
no synthesis of the D-isomer
-
?
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NAD+
-
reverse reaction, one-fifth of that with NADP+
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,2-naphthoquinone
-
-
1-norepinephrine
-
; 3 mM: 30% inhibition
2,4-Dinitrophenol
6,7-Diethylpterin-H2
-
-
6,7-dimethyldihydropterin
-
0.05 mM: 70% inhibition
6,7-dimethyllumazine
-
slight
6,7-dimethylpterin
-
0.05 mM: 46% inhibition; 46% inhibition of the reductive reaction at 0.05 mM
6,7-dimethylpterin-H2
-
70% inhibition of the reductive reaction at 0.05 mM
6-Carboxypterin
6-Hydroxymethylpterin
-
0.05 mM: 23% inhibition; 23% inhibition of the reductive reaction at 0.05 mM
6-methyldihydropterin
-
0.05 mM: 59% inhibition
6-methylpterin
-
10% inhibition of the reductive reaction at 0.05 mM; slight
6-Methylpterin-H2
-
59% inhibition of the reductive reaction at 0.05 mM
7-Methylpterin
-
0.05 mM: 18% inhibition; 18% inhibition of the reductive reaction at 0.05 mM
9,10-phenanthrenequinone
-
-
acetic acid
alpha-ketoglutarate
-
slight, IC50 5 mM
Benzoic acid
-
0.03 mM: 40% inhibition; 40% inhibition of the reductive reaction at 0.03 mM
benzoquinone
-
-
biopterin
-
0.05 mM: 24% inhibition; 24% inhibition of the reductive reaction at 0.05 mM
biopterin-H2
-
31% inhibition of the reductive reaction at 0.05 mM
catecholamine
-
-
Cibacron Blue 3G-A
-
IC50 0.01 mM
D,L-Lactic acid
-
0.03 mM, 20% inhibition
D-erythro-neopterin
-
14% inhibition of the reductive reaction at 0.05 mM
D-erythro-neopterin-H2
-
7% inhibition of the reductive reaction at 0.05 mM
dicoumarol
dihydrobiopterin
dihydroxanthopterin
-
slight
DL-lactic acid
-
20% inhibition of the reductive reaction at 0.03 mM
dopamine
-
slight; slight inhibition
Ethacrynic acid
-
IC50 0.03 mM
Fe3+
-
1 mM inhibits entirely
formic acid
-
slight
Hg2+
-
IC50 0.00009 mM
Indoleamine
-
-
indomethacin
iodoacetate
-
72% inhibition of the reductive reaction at 0.1 mM
Isosepiapterin
-
83% inhibition of the reductive reaction at 0.05 mM; IC50 0.0065 mM, 0.05 mM: 83% inhibition
Isoxanthopterin
-
0.05 mM: very slight
KCN
-
25% inhibition of the reductive reaction at 2.5 mM; slight
L-erythro-dihydroneopterin
-
0.05 mM: 29% inhibition, D-isomer: slight inhibition
-
L-Erythro-neopterin
-
0.05 mM: 21% inhibition, D-isomer: slight inhibition; 21% inhibition of the reductive reaction at 0.05 mM
L-Erythro-neopterin-H2
-
29% inhibition of the reductive reaction at 0.05 mM
Leucopterin
-
0.05 mM: 21% inhibition; 21% inhibition of the reductive reaction at 0.05 mM
Melatonin
monoiodoacetate
-
-
N-acetyl-L-noradrenaline
-
weak inhibitor, N-acetyl-L-adrenaline does not bind enzyme
N-acetyl-p-tyramine
-
weak, N-acetyl-m-tyramine shows strong inhibition
N-acetyl-serotonin
-
complete inhibition
N-acetyldopamine
N-acetylphenethylamine
-
weak
N-acetylserotonin
N-acetyltryptamine
-
slight, N-acetyltryptophan does not bind enzyme
n-butyric acid
-
IC50 0.032 mM, pH 6.5
N-chloroacetyldopamine
-
strong inhibitor
N-chloroacetylserotonin
-
strong competitive inhibitor
N-chloroserotonin
strong inhibitor
N-ethylmaleimide
-
-
N-lactoyldopamine
-
potent inhibitor
N-methoxyacetylserotonin
N-pyruvoyldopamine
-
potent inhibitor
n-valeric acid
-
IC50 0.25 mM, pH 6.5
NADP+
-
competitive inhibition at fixed concentration with varied NADPH, noncompetitive with varied sepiapterin
NaN3
-
15% inhibition of the reductive reaction at 5 mM; slight
NEM
-
35% inhibition of the reductive reaction at 0.1 mM, 88% at 1 mM
oxaloacetate
-
p-chloromercuribenzoate
-
-
p-mercuribenzoate
-
0.1 mM, 93% inhibition
PCMB
-
93% inhibition of the reductive reaction at 0.01 mM
Phenobarbital
-
slight, IC50 0.6 mM
phenylquinone
-
-
Propionamide
-
0.03 mM, 14% inhibition; 14% inhibition of the reductive reaction at 0.03 mM
Propionic acid
pterin
-
0.05 mM: 18% inhibition; 18% inhibition of the reductive reaction at 0.05 mM
pyrazole
-
slight, IC50 1 mM
Pyruvic acid
-
9% inhibition of the reductive reaction at 0.03 mM; slight
rutin
-
IC50 0.06 mM
sepiapterin
serotonin
-
-
Sn2+
-
1 mM inhibits entirely
Sodium acetate
-
-
Xanthopterin
-
slight
Xanthopterin B2
-
slight
Xanthopterin-B2
-
12% inhibition of the reductive reaction at 0.05 mM
xanthopterin-H2
-
9% inhibition of the reductive reaction at 0.05 mM
Zn2+
-
IC50 0.4 mM
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
the enzyme activity is not affected by laminar shear stress in endothelial cells, overview
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.007
1'-hydroxy-2'-oxopropyltetrahydropterin
-
pH 7.4, 37C
-
0.0021
1,2-naphthoquinone
-
wild-type, pH 6.4, 37C
0.027
1,4-Naphthoquinone
-
wild-type, pH 6.4, 37C
0.118
1-phenyl-1,2-propanedione
-
cofactor NADH
0.086
2,3-dimethoxynaphthalene-1,4-dione
-
wild-type, pH 6.4, 37C
5.19
2,4-Pentanedione
-
-
0.0143
2-amino-6-(2-hydroxypropanoyl)pteridin-4(1H)-one
-
pH 6.4, 25C
0.0077
7,8-dihydrobiopterin
-
pH 10.4, 25C
0.00082
9,10-phenanthrene quinone
-
-
0.0019 - 0.464
9,10-phenanthrenequinone
29
acetoin
-
-
1.1
acetophenone
-
-
0.0183 - 0.02
benzil
0.043
benzylacetone
-
-
1 - 4
diacetyl
0.057
dihydrobiopterin
-
at pH 10.4
0.008
lactoyltetrahydropterin
-
pH 7.4, 37C
0.0872 - 0.18
menadione
4.4
methylglyoxal
-
-
0.0057 - 0.077
NADP+
0.0014 - 0.052
NADPH
0.43
p-nitrobenzaldehyde
-
-
0.75
p-quinone
-
-
0.59
Phenylglyoxal
-
-
0.0218
phenylpropanedione
-
; pH 6.4, 25C
0.14
propiophenone
-
-
0.002
pyruvoyltetrahydropterin
-
pH 7.4, 37C
0.00018 - 0.169
sepiapterin
additional information
additional information
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.627
1,2-naphthoquinone
Homo sapiens
-
wild-type, pH 6.4, 37C
0.45
1,4-Naphthoquinone
Homo sapiens
-
wild-type, pH 6.4, 37C
1.43
2,3-dimethoxynaphthalene-1,4-dione
Homo sapiens
-
wild-type, pH 6.4, 37C
0.0048 - 0.805
9,10-phenanthrenequinone
1.45
menadione
Homo sapiens
-
wild-type, pH 6.4, 37C
0.0053 - 1.61
sepiapterin
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3.1 - 3.4
1-norepinephrine
0.0009
benzoquinone
-
wild-type, pH 6.7, 37C
0.0027
indomethacin
-
wild-type, pH 6.7, 37C
0.025 - 0.03
Melatonin
0.00017 - 0.0002
N-acetyl-serotonin
0.0009
N-acetylserotonin
-
wild-type, pH 6.7, 37C
0.0005
phenylquinone
-
wild-type, pH 6.7, 37C
2.3 - 2.5
serotonin
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0089
1,2-naphthoquinone
Homo sapiens
-
wild-type, pH 6.7, 37C
0.014 - 0.03
6-Carboxypterin
0.0036
9,10-phenanthrenequinone
Homo sapiens
-
wild-type, pH 6.7, 37C
0.45
acetic acid
Equus caballus
-
IC50 0.45 mM, pH 6.5
5
alpha-ketoglutarate
Rattus norvegicus
-
slight, IC50 5 mM
0.0028
benzoquinone
Homo sapiens
-
wild-type, pH 6.7, 37C
0.1
Cd2+
Rattus norvegicus
-
IC50 0.1 mM
0.01
Cibacron Blue 3G-A
Rattus norvegicus
-
IC50 0.01 mM
0.0002 - 0.0006
dicoumarol
0.03
Ethacrynic acid
Rattus norvegicus
-
IC50 0.03 mM
0.00009
Hg2+
Rattus norvegicus
-
IC50 0.00009 mM
0.0081 - 0.06
indomethacin
0.0065
Isosepiapterin
Equus caballus
-
IC50 0.0065 mM, 0.05 mM: 83% inhibition
0.1
Melatonin
Bombyx mori
-
recombinant enzyme, in 100 mM potassium phosphate buffer (pH 6.4), at 37C
0.0006 - 0.2
N-acetylserotonin
0.032
n-butyric acid
Equus caballus
-
IC50 0.032 mM, pH 6.5
0.25
n-valeric acid
Equus caballus
-
IC50 0.25 mM, pH 6.5
0.6
Phenobarbital
Rattus norvegicus
-
slight, IC50 0.6 mM
0.0016
phenylquinone
Homo sapiens
-
wild-type, pH 6.7, 37C
0.0045 - 0.3
Propionic acid
1
pyrazole
Rattus norvegicus
-
slight, IC50 1 mM
0.06
rutin
Rattus norvegicus
-
IC50 0.06 mM
0.4
Zn2+
Rattus norvegicus
-
IC50 0.4 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.022
-
measured in female flies, value lower in males
0.93
-
-
1.7
-
in Escherichia coli HB101, transformed with pBLY1 containing sepiapterin reductase cDNA
1.8
-
pH 6.7, 37C
9.76
-
-
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
-
assay at
8.6
-
optimum of isomerization of 6-1'-oxo-2'-hydroxypropyl(6-lactoyltetrahydropterin) to 6-1'-hydroxy-2'-oxopropyltetrahydropterin
8.8
-
in Tris-HCl buffer or in glycine-NaOH buffer
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4 - 6
-
-
5.5 - 7.4
-
pH 5.5: optimum, pH 7.4: in 50 mM Tris-HCl buffer about 80% of maximum activity observed
5.7 - 6.7
-
optimium for activity, highest activity in phosphate buffer
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
-
assay at
25 - 30
-
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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monoaminergic field, neurons
Manually annotated by BRENDA team
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post-mortem semi-quantitative expression analysis in brain of control individuals and Parkinson disease patients, SPR expression is increased in Parkinson patients, but not in the other genes involved in the tetrahydrobiopterin biosynthesis, overview
Manually annotated by BRENDA team
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pyramidal neurons
Manually annotated by BRENDA team
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neurons
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
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dorsal and ventral parts
Manually annotated by BRENDA team
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no enzyme detectable
Manually annotated by BRENDA team
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neurons
Manually annotated by BRENDA team
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cell culture model for catecholaminergic neurons
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
92% of total activity
Manually annotated by BRENDA team
additional information
-
intracellular localization, overview
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
28000
-
SDS-PAGE
29200
-
calculated from amino acid sequence
39000
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gel filtration, nondissociating PAGE
45300
-
gel filtration
59000
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
monomer
additional information
-
structure-function relationship, amino acid sequence comparison of several species
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
purified native and selenomethionine-labeled enzyme alone and in complex with NADP+ and sepiapterin, hanging drop vapour diffusion method, 18C, 0.004 ml protein solution, with or without 10 mM NADP+ and sepiapterin, is mixed with 0.001 ml of a mixture of 0.004 ml or reservoir solution containing 0.2 M MgCl2, 0.1 M Tris-HCl, pH 8.5, and 34% PEG 400, and 0.001 ml additive solution 1 M guanidinium hydrochloride, X-ray diffraction structure determination and analysis at 2.1 A and 1.7 A resolution, respectively
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purified native and selenomethionine-labeled enzyme, hanging drop vapour diffusion microbatch method, 18C, 0.004 ml protein solution containing 10 mg/ml protein in 20 mM Tris-HCl, pH 8.0, is mixed with 0.001 ml of a mixture of 0.004 ml or reservoir solution containing 0.2 M MgCl2, 0.1 M Tris-HCl, pH 8.5, and 34% PEG 400, and 0.001 ml additive solution 1 M guanidinium hydrochloride, 2 days, X-ray diffraction structure determination and analysis at 2.1 A resolution
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vapour diffusion technique
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25 - 50
-
relativley stable for 2 h in this range, loss of activity in 20 min at 70C
48
-
half of activity remains within 30 min
72
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the melting temperature of the wild type enzyme is at 72.77C
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
bovine serum albumin stabilizes
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NADP+ stabilizes
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-15C, in 150 mM Tris-HCl buffer, pH 6.0, second hydroxylapatite fraction, for 1 week, relatively little loss of activity
-
-15C, purified enzyme, 0.01 M potassium phosphate buffer, pH 6.0, stable for 1 week with little loss of activity
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-40C, in 50 mM potassium phosphate buffer, pH 6.9, at least stable for two months
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-70C, after dialyzation against Pipes, pH 7.5, 10% glycerol
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-70C, desalted extracts, several weeks without significant loss of activity
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-70C, in 20 mM Tris-HCl, pH 8.8
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-80C, in 50 mM potassium phosphate buffer, 0,1 M KCl, pH 6.8
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20C, after ion exchange chromatography, no change in activity over one year of storage
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
; native enzyme from erythrocytes
-
; native enzyme from erythrocytes by hydroxylapatite and NADP+-affinity chromatography, to homogeneity
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brain, partially, from erythrocytes to homogeneity; native enzyme partially from brain by ammonium sulfate fractionation and hydroxylapatite chromatography, and from erythrocytes to homogeneity by affinity chromatography and isoelectric focusing
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His GraviTrap nickel affinity column chromatography, gel filtration
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liver, partially
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liver; native enzyme 5000fold from liver by ammonium sulfate and protamine sulfate fractionation, and two times treatment by hydroxylapatite and anion exchange chromatography
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Ni-NTA bead chromatography, MonoQ column chromatography, and Superdex 200 gel filtration
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recombinant His-tagged native and selenomethionine-labeled enzyme from Escherichia coli strain BL21(DE3) by nickel affinity and anion exchange chromatography, followed by gel filtration
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recombinant protein of Escherichia coli
recombinant protein using His-tag
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
chromosomal location 2p14-2p12, RT-PCR expression analysis
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expressed in COS-7 and RNA-64A cells
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expressed in Escherichia coli
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expressed in Escherichia coli BL21 (DE3) cells
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expressed in Escherichia coli BL21(DE3) cells
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expressed in Escherichia coli BL21(DE3)/pLysS
expressed in Escherichia coli BL21(DE3, pLysS)
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expression of His-tagged native and selenomethionine-labeled enzyme in Escherichia coli strain BL21(DE3)
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gene SPR, chromosomal location at 2p13, genomic structure, DNA and amino acid sequence determination of wild-type and mutant enzymes
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host cells transfected with sense, antisense and inverse antisense oligodeoxynucleotides
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recombinant protein expressed in Escherichia coli
site-directed mutagenesis, recombinant protein expressed in Escherichia coli GI724
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
F99A
-
the mutant shows 3.9fold higher Km and lower Vmax (8.95%) than the wild type enzyme
W196A
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the mutant shows 8.7fold higher Km and lower Vmax (5.64%) than the wild type enzyme
D257H
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mutant shows completely inhibited sepiapterin reduction. Mutation has only minimal effects on redox cycling
DELTA257-261
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deletion of the C-terminal 5 amino acids almost completely eliminates enzyme activity. For redox cycling, the catalytic efficacy decreases to less than 1% of the wild type enzyme
G14S
-
mutations in Gly14 and Gly18 in the NADPH binding motif of sepiapterin reductase results in almost complete loss of the ability to reduce sepiapterin, and a 65-75% decrease in redox cycling. For both of these mutations, the catalytic efficiencies for redox cycling decreases to 0.2% of wild type sepiapterin reductase
G18D
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mutations in Gly14 and Gly18 in the NADPH binding motif of sepiapterin reductase results in almost complete loss of the ability to reduce sepiapterin, and a 65-75% decrease in redox cycling. For both of these mutations, the catalytic efficiencies for redox cycling decreases to 0.2% of wild type sepiapterin reductase
K174L
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catalytic efficiencies (Kcat/Km) for sepiapterin reduction of S157A mutant and K174L mutant decreases to 1.8% and 0.8% of wild type sepiapterin reductase, respectively, and for redox cycling to 6.8% and 1.4%, respectively
K251X
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naturally occurring mutation in gene SPR, exon 3, causing enzyme deficiency
M205G
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mutation leads to marked reductions in the activities of both sepiapterin reduction and redox cycling. The catalytic efficiency of N99A and M205G for sepiapterin reduction decreases to approximately 1% and 5%, respectively, and for redox cycling, 5% and 25%, respectively, when compared to the wild type enzyme
N99A
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mutation leads to marked reductions in the activities of both sepiapterin reduction and redox cycling. The catalytic efficiency of N99A and M205G for sepiapterin reduction decreases to approximately 1% and 5%, respectively, and for redox cycling, 5% and 25%, respectively, when compared to the wild type enzyme
P163L
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naturally occurring mutation in gene SPR, exon 2, causing enzyme deficiency
Q119X
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naturally occurring mutation in gene SPR, exon 2, causing enzyme deficiency
R150fs
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naturally occurring mutation in gene SPR, exon 2, causing enzyme deficiency
R150G
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naturally occurring mutation in gene SPR, exon 2, causing enzyme deficiency
R42G
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mutation leads to a 90% reduction in sepiapterin reduction activity and a 50% reduction in redox cycling activity. The catalytic efficiencies for this mutant decreases to 2% and 7% of wild type sepiapterin reductase for sepiapterin reduction and redox cycling, respectively
S157A
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catalytic efficiencies (Kcat/Km) for sepiapterin reduction of S157A mutant and K174L mutant decreases to 1.8% and 0.8% of wild type sepiapterin reductase, respectively, and for redox cycling to 6.8% and 1.4%, respectively
Y259A
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mutation of Tyr259, a unique potential phosphorylation site in the C-terminal substrate transfer motif, has no major effects on sepiapterin reduction and redox cycling activity
K175I
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decreased activity against a pteridine substrate and exogenous carbonyl compound
S158D
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decreased activity against a pteridine substrate and exogenous carbonyl compound
S158D/Y171V
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double-point mutant does not show any activity towards any substrate
Y171V
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decreased activity against a pteridine substrate and exogenous carbonyl compound
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
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polymorphisms of sepiapterin reductase gene alter promoter activity and may influence risk of bipolar disorder