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Information on EC 1.1.1.153 - sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming) and Organism(s) Homo sapiens
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1.1.1.153 sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)IUBMB Comments
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).
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Word Map
- 1.1.1.153
- tetrahydrobiopterin
- bh4
-
aldo-keto
-
cyclohydrolase
- aldose
-
neurotransmitter
- pterins
-
dopa-responsive
- tetrahydropterins
- 6-pyruvoyl-tetrahydropterin
- n-acetylserotonin
- dystonia
- dihydropteridine
- dihydroneopterin
-
6-pyruvoyl
- pteridine
- neopterin
- gtpch
- ptges
-
gtp-cyclohydrolase
- 5-hydroxytryptophan
- akr1b3
- 6r-5,6,7,8-tetrahydrobiopterin
- epalrestat
- hyperphenylalaninaemia
-
segawa
- 2,4-diamino-6-hydroxypyrimidine
- medicine
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Synonyms
akr1b1, sepiapterin reductase, mdspr, mdspi16 protein, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
reductase, sepiapterin
-
-
-
-
sepiapterin reductase
SPR
SPR
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
KEGG
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
9059-48-7
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
1'-oxo-2'-hydroxypropyl-tetrahydropterin + NADPH + H+
tetrahydrobiopterin + NADP+
-
-
-
?
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
6-pyruvoyl tetrahydropterin + 2 NADPH + 2 H+
tetrahydrobiopterin + NADP+
-
-
-
-
?
6-pyruvoyl tetrahydropterin + NADPH + H+
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
-
-
-
-
?
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
-
-
?
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
-
-
?
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
-
-
?
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
-
-
?
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
terminal step in the biosynthetic pathway for tetrahydrobiopterin
-
?
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
terminal step in the biosynthetic pathway for tetrahydrobiopterin
-
?
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
terminal step in the biosynthetic pathway for tetrahydrobiopterin
-
?
6-pyruvoyl-5,6,7,8-tetrahydropterin + NADPH
tetrahydrobiopterin + NADP+
-
-
-
-
r
6-pyruvoyl-5,6,7,8-tetrahydropterin + NADPH
tetrahydrobiopterin + NADP+
-
-
the cofactor for aromatic amino acid hydrolases in the biosynthesis of aromatc amino acids and dopamine
-
r
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
-
cellular uptake of sepiapterin across the cell membrane results in an efficient accumulation of tetrahydrobiopterin, sepiapterin relocates across the plasma membrane via two distinct paths, the slower path connects to the cytosolic compartment, overview
-
-
r
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
no stereochemic specification in the publication
-
-
?
sepiapterin + NADPH + H+
tetrahydrobiopterin + NADP+
-
no stereochemic specification in the publication
-
?
sepiapterin + NADPH + H+
tetrahydrobiopterin + NADP+
-
-
no stereochemic specification in the publication
-
?
sepiapterin + NADPH + H+
tetrahydrobiopterin + NADP+
-
no stereochemic specification of the substrate in the publication
-
?
additional information
?
-
-
final step in the synthesis of tetrahydrobiopterin
-
-
?
additional information
?
-
-
the enzyme is involved in the tetrahydrobiopterin biosynthesis
-
-
?
additional information
?
-
-
sepiapterin or dihydrobiopterin are the precursors of the tetrahydrobiopterin-salvage pathway, enzyme activity and pathway regulation in vivo, overview
-
-
?
additional information
?
-
-
the enzyme catalyzes the final step in the tetrahydrobiopterin biosynthesis
-
-
?
additional information
?
-
-
the enzyme catalyzes the final step in the tetrahydrobiopterin biosynthesis, sepiapterin reductase expression is increased in Parkinsons disease brain tissue
-
-
?
additional information
?
-
native ornithine decarboxylase, EC 4.1.1.17, and sepiapterin reductase physically interact, in silico protein-protein docking simulations
-
-
?
additional information
?
-
-
native ornithine decarboxylase, EC 4.1.1.17, and sepiapterin reductase physically interact, in silico protein-protein docking simulations
-
-
?
additional information
?
-
physical interaction between key polyamines biosynthesis enzyme ornithine decarboxylase (ODC) and sepiapterin reductase (SPR)
-
-
?
additional information
?
-
-
physical interaction between key polyamines biosynthesis enzyme ornithine decarboxylase (ODC) and sepiapterin reductase (SPR)
-
-
?
additional information
?
-
the enzyme's one-electron reduction of redox cycling chemicals, such as menadione, generates radical cations. The rapid reaction of these cations with molecular oxygen regenerates the redox active chemical, and in the process superoxide anion is formed. Sepiapterin reduction is catalyzed by NADPH, whereas chemical redox cycling is catalyzed by NADPH and/or NADH, overview
-
-
?
additional information
?
-
-
the enzyme's one-electron reduction of redox cycling chemicals, such as menadione, generates radical cations. The rapid reaction of these cations with molecular oxygen regenerates the redox active chemical, and in the process superoxide anion is formed. Sepiapterin reduction is catalyzed by NADPH, whereas chemical redox cycling is catalyzed by NADPH and/or NADH, overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
1'-oxo-2'-hydroxypropyl-tetrahydropterin + NADPH + H+
tetrahydrobiopterin + NADP+
-
-
-
?
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
-
-
?
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
terminal step in the biosynthetic pathway for tetrahydrobiopterin
-
?
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
terminal step in the biosynthetic pathway for tetrahydrobiopterin
-
?
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
terminal step in the biosynthetic pathway for tetrahydrobiopterin
-
?
6-pyruvoyl-5,6,7,8-tetrahydropterin + NADPH
tetrahydrobiopterin + NADP+
-
-
-
-
r
6-pyruvoyl-5,6,7,8-tetrahydropterin + NADPH
tetrahydrobiopterin + NADP+
-
-
the cofactor for aromatic amino acid hydrolases in the biosynthesis of aromatc amino acids and dopamine
-
r
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
-
cellular uptake of sepiapterin across the cell membrane results in an efficient accumulation of tetrahydrobiopterin, sepiapterin relocates across the plasma membrane via two distinct paths, the slower path connects to the cytosolic compartment, overview
-
-
r
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
no stereochemic specification in the publication
-
-
?
sepiapterin + NADPH + H+
tetrahydrobiopterin + NADP+
-
no stereochemic specification in the publication
-
?
sepiapterin + NADPH + H+
tetrahydrobiopterin + NADP+
-
-
no stereochemic specification in the publication
-
?
additional information
?
-
-
final step in the synthesis of tetrahydrobiopterin
-
-
?
additional information
?
-
-
the enzyme is involved in the tetrahydrobiopterin biosynthesis
-
-
?
additional information
?
-
-
sepiapterin or dihydrobiopterin are the precursors of the tetrahydrobiopterin-salvage pathway, enzyme activity and pathway regulation in vivo, overview
-
-
?
additional information
?
-
-
the enzyme catalyzes the final step in the tetrahydrobiopterin biosynthesis
-
-
?
additional information
?
-
-
the enzyme catalyzes the final step in the tetrahydrobiopterin biosynthesis, sepiapterin reductase expression is increased in Parkinsons disease brain tissue
-
-
?
additional information
?
-
native ornithine decarboxylase, EC 4.1.1.17, and sepiapterin reductase physically interact, in silico protein-protein docking simulations
-
-
?
additional information
?
-
-
native ornithine decarboxylase, EC 4.1.1.17, and sepiapterin reductase physically interact, in silico protein-protein docking simulations
-
-
?
additional information
?
-
physical interaction between key polyamines biosynthesis enzyme ornithine decarboxylase (ODC) and sepiapterin reductase (SPR)
-
-
?
additional information
?
-
-
physical interaction between key polyamines biosynthesis enzyme ornithine decarboxylase (ODC) and sepiapterin reductase (SPR)
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(1s,4s)-4-[(2E)-2-[(4-fluorobenzoyl)imino]-6-[(piperidin-1-yl)methyl]-2,3-dihydro-1H-benzimidazol-1-yl]cyclohexane-1-carboxylic acid
-
(2,4-dichloro-6-hydroxyphenyl)(2-methyl-2,3-dihydro-1H-indol-1-yl)methanone
-
(2,4-dichloro-6-hydroxyphenyl)(2-methyl-2,6-diazaspiro[3.4]octan-6-yl)methanone
-
(2,4-dichloro-6-hydroxyphenyl)(2-oxa-6-azaspiro[3.4]octan-6-yl)methanone
-
(2,4-dichloro-6-hydroxyphenyl)(3,4-dihydroisoquinolin-2(1H)-yl)methanone
-
(2,4-dichloro-6-hydroxyphenyl)(3-fluoro-3-methylpyrrolidin-1-yl)methanone
-
(2,4-dichloro-6-hydroxyphenyl)[3-(1-methyl-1H-pyrazol-4-yl)pyrrolidin-1-yl]methanone
-
(2,4-dichloro-6-hydroxyphenyl)[3-(2-phenylethyl)pyrrolidin-1-yl]methanone
-
(2,4-dichloro-6-hydroxyphenyl)[3-(pyridin-2-yl)pyrrolidin-1-yl]methanone
-
(2,4-dichloro-6-hydroxyphenyl)[3-(pyridin-3-yl)pyrrolidin-1-yl]methanone
-
(2,4-dichloro-6-hydroxyphenyl)[3-(pyridin-4-yl)pyrrolidin-1-yl]methanone
-
(2,4-dichloro-6-hydroxyphenyl)[3-(trifluoromethyl)pyrrolidin-1-yl]methanone
-
(2,4-dichloro-6-hydroxyphenyl)[3-[(pyridin-3-yl)methyl]pyrrolidin-1-yl]methanone
-
(2,4-dichloro-6-hydroxyphenyl)[3-[(pyridin-3-yl)oxy]pyrrolidin-1-yl]methanone
-
(2,4-dichloro-6-hydroxyphenyl)[3-[(pyridin-4-yl)methyl]pyrrolidin-1-yl]methanone
-
(2-hydroxyphenyl)[3-methyl-1-(pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl]methanone
-
(4S)-4-(8-hydroxyquinolin-2-yl)-1-methyl-3-(pyridin-3-yl)-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one
-
(6-azaspiro[3.4]octan-6-yl)(2,4-dichloro-3-fluoro-6-hydroxyphenyl)methanone
-
(6-azaspiro[3.4]octan-6-yl)(2-chloro-4-fluoro-6-hydroxyphenyl)methanone
-
(6-azaspiro[3.4]octan-6-yl)(2-chloro-6-hydroxy-4-methoxyphenyl)methanone
-
(6-azaspiro[3.4]octan-6-yl)(2-chloro-6-hydroxy-4-methylphenyl)methanone
-
(6-azaspiro[3.4]octan-6-yl)(2-fluoro-6-hydroxy-4-methylphenyl)methanone
-
(6-azaspiro[3.4]octan-6-yl)(4-chloro-2-fluoro-6-hydroxyphenyl)methanone
-
(6-azaspiro[3.4]octan-6-yl)(4-chloro-2-hydroxy-6-methylphenyl)methanone
-
(6-azaspiro[3.4]octan-6-yl)[2-chloro-4-(dimethylamino)-6-hydroxyphenyl]methanone
-
(6-azaspiro[3.4]octan-6-yl)[2-chloro-6-hydroxy-4-(trifluoromethyl)phenyl]methanone
-
2,7,10-trimethyl-9-(4-methyl-2,6-dioxocyclohexane-1-carbonyl)-4,5-dihydro-6lambda6-[1]benzothiepino[5,4-c]pyrazole-6,6(2H)-dione
-
3-chloro-1-[2-methoxy-4-(trifluoromethyl)phenyl]-N-(1,3-thiazol-2-yl)isoquinoline-6-sulfonamide
-
3-hydroxy-4,4-dimethyl-1-oxo-N7-(2-phenylethyl)-1,4-dihydronaphthalene-2,7-dicarboxamide
-
3-[1-(3-propyl-1H-pyrazole-5-carbonyl)piperidin-4-yl]-3,4-dihydro-1lambda6,2,4-benzothiadiazine-1,1(2H)-dione
-
4-(4-[4-[4-(trifluoromethoxy)phenyl]-4H-1,2,4-triazol-3-yl]piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidine
-
4-fluoro-N-[(2E)-1-[4-[(propan-2-yl)carbamoyl]cyclohexyl]-6-[(1H-1,2,4-triazol-1-yl)methyl]-1,3-dihydro-2H-benzimidazol-2-ylidene]benzamide
-
4-[(1,3-thiazol-2-yl)sulfamoyl]-N-[3-(trifluoromethyl)phenyl]piperidine-1-carboxamide
-
4-[2-(pyridin-4-yl)ethyl]-N-(1,3-thiazol-2-yl)-3,4-dihydro-2H-1,4-benzoxazine-7-sulfonamide
-
7-(3,4-dihydroxyphenyl)-5-hydroxy-10-(2-hydroxyethyl)-2,2-dimethyl-2H,6H-benzo[1,2-b:5,4-b']dipyran-6-one
-
alpha-difluoromethylornithine
DFMO, IC50 value of 4.07 mM for SK-N-Be(2)c and 5.79 mM for LAN-5 cells
alpha-difluoromethylornitine
the combination of sulfasalazine with alpha-difluoromethylornitine produces synergistic antiproliferative effects on neuroblastoma cells in vitro
Chlorpropamide
noncompetitive; noncompetitive inhibition in sepiapterin reduction and redox cycling
ethyl 6'-chloro-2'-hydroxy-4-(2-methoxy-2-oxoethylidene)-4'-oxo-4'H-spiro[cyclohexane-1,1'-naphthalene]-3'-carboxylate
-
ethyl N-[(6-bromo-5-methoxy-1-methyl-3-propanoyl-1H-indol-2-yl)methyl]glycinate
-
glibenclamide
noncompetitive inhibition in sepiapterin reduction and redox cycling
N-(5-fluoropyridin-2-yl)-1-[2-hydroperoxy-4-(trifluoromethyl)phenyl]isoquinoline-6-sulfonamide
-
N-[2-chloro-4-(1-ethyl-5-hydroxy-1H-pyrazole-4-carbonyl)-5-methoxyphenyl]-N,N',N'-trimethylsulfuric diamide
-
N2-(3-chlorophenyl)-N-[(1r,4r)-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)cyclohexyl]-N2-(pyridine-3-sulfonyl)glycinamide
-
Tolbutamide
noncompetitive inhibition in sepiapterin reduction and redox cycling
[4-(benzenesulfonyl)piperidin-1-yl](2,4-dichloro-6-hydroxyphenyl)methanone
-
N-acetylserotonin
-
0.05 mM, 90% inhibition of enzyme from stimulated mononuclear blood cells
N-acetylserotonin
-
activity is completely inhibited by the addition of 0.5 mM N-acetylserotonin
sulfamethoxazole
noncompetitive; noncompetitive inhibition in sepiapterin reduction and redox cycling
sulfapyridine
noncompetitive; noncompetitive inhibition in sepiapterin reduction and redox cycling
sulfasalazine
i.e. 5-((4-(2-pyridylsulfamoyl) phenyl)azo) salicylic acid or 2-hydroxy-5-[(E)-2-{4-[(pyridin-2-yl)sulfamoyl]phenyl}diazen-1-yl]benzoic acid or SSZ, an FDA-approved salicylate-based anti-inflammatory and immuno-modulatory drug, inhibits sepiapterin reductase. Computational docking of inhibitor sulfasalazine into sepiapterin reductase. The receptor pocket comprises residues Gly11, Ser13, Arg14, Phe16 (region 1), Ala38, Arg39 (region 2), Asn97, Ala98, Gly99, Ser100 (region 3), Tyr167 (region 4), and Leu198, Thr200, Met202 (region 5). Sulfasalazine exhibits an IC50 value of 0.133 mM for SK-N-Be(2)c and 0.337 mM for LAN-5 cells; inhibits the growth of neuroblastoma cells in vitro, presumably due to the inhibition of sepiapterin reductase as predicted by computational docking of sulfasalazine into sepiapterin reductase. The combination of sulfasalazine with alpha-difluoromethylornitine produces synergistic antiproliferative effects in vitro
sulfasalazine
noncompetitive; noncompetitive inhibition in sepiapterin reduction and redox cycling
sulfathiazole
noncompetitive; noncompetitive inhibition in sepiapterin reduction and redox cycling
additional information
-
the enzyme activity is not affected by laminar shear stress in endothelial cells, overview
-
additional information
synergism of sulfasalazine and alpha-difluoromethylornithine (DFMO) combination treatment in neuroblastoma cells
-
additional information
-
synergism of sulfasalazine and alpha-difluoromethylornithine (DFMO) combination treatment in neuroblastoma cells
-
additional information
sulfonylurea- or sulfonamide-based drugs inhibit sepiapterin reduction and chemical redox cycling by sepiapterin reductase
-
additional information
-
sulfonylurea- or sulfonamide-based drugs inhibit sepiapterin reduction and chemical redox cycling by sepiapterin reductase
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
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
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00256
(2,4-dichloro-6-hydroxyphenyl)(1,3-dihydro-2H-isoindol-2-yl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00012
(2,4-dichloro-6-hydroxyphenyl)(2,3-dihydro-1H-indol-1-yl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00244
(2,4-dichloro-6-hydroxyphenyl)(2-methyl-2,3-dihydro-1H-indol-1-yl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.01
(2,4-dichloro-6-hydroxyphenyl)(2-methyl-2,6-diazaspiro[3.4]octan-6-yl)methanone
Homo sapiens
IC50 above 0.01 mM, at pH 7.4, temperature not specified in the publication
0.00168
(2,4-dichloro-6-hydroxyphenyl)(2-oxa-6-azaspiro[3.4]octan-6-yl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.0051
(2,4-dichloro-6-hydroxyphenyl)(3,3-dimethylpyrrolidin-1-yl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00021
(2,4-dichloro-6-hydroxyphenyl)(3,4-dihydroisoquinolin-2(1H)-yl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00068
(2,4-dichloro-6-hydroxyphenyl)(3,4-dihydroquinolin-1(2H)-yl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00527
(2,4-dichloro-6-hydroxyphenyl)(3-fluoro-3-methylpyrrolidin-1-yl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00052
(2,4-dichloro-6-hydroxyphenyl)(3-phenylpyrrolidin-1-yl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00024
(2,4-dichloro-6-hydroxyphenyl)(4-phenylpiperidin-1-yl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00199
(2,4-dichloro-6-hydroxyphenyl)(pyrrolidin-1-yl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.0006
(2,4-dichloro-6-hydroxyphenyl)[3-(1-methyl-1H-pyrazol-4-yl)pyrrolidin-1-yl]methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00038
(2,4-dichloro-6-hydroxyphenyl)[3-(2-phenylethyl)pyrrolidin-1-yl]methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00079
(2,4-dichloro-6-hydroxyphenyl)[3-(pyridin-2-yl)pyrrolidin-1-yl]methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00037
(2,4-dichloro-6-hydroxyphenyl)[3-(pyridin-3-yl)pyrrolidin-1-yl]methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00062
(2,4-dichloro-6-hydroxyphenyl)[3-(pyridin-4-yl)pyrrolidin-1-yl]methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00131
(2,4-dichloro-6-hydroxyphenyl)[3-(trifluoromethyl)pyrrolidin-1-yl]methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00061
(2,4-dichloro-6-hydroxyphenyl)[3-[(pyridin-3-yl)methyl]pyrrolidin-1-yl]methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00031
(2,4-dichloro-6-hydroxyphenyl)[3-[(pyridin-3-yl)oxy]pyrrolidin-1-yl]methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00055
(2,4-dichloro-6-hydroxyphenyl)[3-[(pyridin-4-yl)methyl]pyrrolidin-1-yl]methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00478
(2-azaspiro[3.4]octan-2-yl)(2,4-dichloro-6-hydroxyphenyl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.0024
(2-azaspiro[4.4]nonan-2-yl)(2,4-dichloro-6-hydroxyphenyl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00585
(2-azaspiro[4.5]decan-2-yl)(2,4-dichloro-6-hydroxyphenyl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00028
(3-anilinopyrrolidin-1-yl)(2,4-dichloro-6-hydroxyphenyl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00074
(3-benzylpyrrolidin-1-yl)(2,4-dichloro-6-hydroxyphenyl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00031
(4-benzylpiperidin-1-yl)(2,4-dichloro-6-hydroxyphenyl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00098
(5-azaspiro[2.4]heptan-5-yl)(2,4-dichloro-6-hydroxyphenyl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.000057
(6-aza-spiro[3.4]oct-6-yl)-(2,4-difluoro-6-hydroxyphenyl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00748
(6-azaspiro[3.4]octan-6-yl)(2,3-dichloro-6-hydroxyphenyl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00157
(6-azaspiro[3.4]octan-6-yl)(2,4-dichloro-3-fluoro-6-hydroxyphenyl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00058
(6-azaspiro[3.4]octan-6-yl)(2,4-dichloro-6-hydroxyphenyl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.01
(6-azaspiro[3.4]octan-6-yl)(2,4-dichloro-6-methoxyphenyl)methanone
Homo sapiens
IC50 above 0.01 mM, at pH 7.4, temperature not specified in the publication
0.00067
(6-azaspiro[3.4]octan-6-yl)(2-chloro-4-fluoro-6-hydroxyphenyl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.01
(6-azaspiro[3.4]octan-6-yl)(2-chloro-6-hydroxy-4-methoxyphenyl)methanone
Homo sapiens
IC50 above 0.01 mM, at pH 7.4, temperature not specified in the publication
0.01
(6-azaspiro[3.4]octan-6-yl)(2-chloro-6-hydroxy-4-methylphenyl)methanone
Homo sapiens
IC50 above 0.01 mM, at pH 7.4, temperature not specified in the publication
0.00145
(6-azaspiro[3.4]octan-6-yl)(2-chloro-6-hydroxyphenyl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.01
(6-azaspiro[3.4]octan-6-yl)(2-fluoro-6-hydroxy-4-methylphenyl)methanone
Homo sapiens
IC50 above 0.01 mM, at pH 7.4, temperature not specified in the publication
0.00029
(6-azaspiro[3.4]octan-6-yl)(2-fluoro-6-hydroxyphenyl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.01
(6-azaspiro[3.4]octan-6-yl)(2-hydroxypyridin-3-yl)methanone
Homo sapiens
IC50 above 0.01 mM, at pH 7.4, temperature not specified in the publication
0.01
(6-azaspiro[3.4]octan-6-yl)(3,4-dichloro-2-hydroxyphenyl)methanone
Homo sapiens
IC50 above 0.01 mM, at pH 7.4, temperature not specified in the publication
0.01
(6-azaspiro[3.4]octan-6-yl)(3,6-dichloro-2-hydroxyphenyl)methanone
Homo sapiens
IC50 above 0.01 mM, at pH 7.4, temperature not specified in the publication
0.01
(6-azaspiro[3.4]octan-6-yl)(3-chloro-5-hydroxypyridin-4-yl)methanone
Homo sapiens
IC50 above 0.01 mM, at pH 7.4, temperature not specified in the publication
0.00061
(6-azaspiro[3.4]octan-6-yl)(3-hydroxypyridin-2-yl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.01
(6-azaspiro[3.4]octan-6-yl)(3-hydroxypyridin-4-yl)methanone
Homo sapiens
IC50 above 0.01 mM, at pH 7.4, temperature not specified in the publication
0.01
(6-azaspiro[3.4]octan-6-yl)(4,5-dichloro-2-hydroxyphenyl)methanone
Homo sapiens
IC50 above 0.01 mM, at pH 7.4, temperature not specified in the publication
0.00772
(6-azaspiro[3.4]octan-6-yl)(4-chloro-2-fluoro-6-hydroxyphenyl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.01
(6-azaspiro[3.4]octan-6-yl)(4-chloro-2-hydroxy-6-methylphenyl)methanone
Homo sapiens
IC50 above 0.01 mM, at pH 7.4, temperature not specified in the publication
0.00404
(6-azaspiro[3.4]octan-6-yl)(4-chloro-2-hydroxyphenyl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.01
(6-azaspiro[3.4]octan-6-yl)(4-fluoro-2-hydroxyphenyl)methanone
Homo sapiens
IC50 above 0.01 mM, at pH 7.4, temperature not specified in the publication
0.01
(6-azaspiro[3.4]octan-6-yl)(4-hydroxypyridin-3-yl)methanone
Homo sapiens
IC50 above 0.01 mM, at pH 7.4, temperature not specified in the publication
0.00031
(6-azaspiro[3.4]octan-6-yl)(5-chloro-3-hydroxypyridin-2-yl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00035
(6-azaspiro[3.4]octan-6-yl)(5-fluoro-3-hydroxypyridin-2-yl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00155
(6-azaspiro[3.4]octan-6-yl)(5-hydroxypyrimidin-4-yl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00232
(6-azaspiro[3.4]octan-6-yl)[2-chloro-4-(dimethylamino)-6-hydroxyphenyl]methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.01
(6-azaspiro[3.4]octan-6-yl)[2-chloro-6-hydroxy-4-(trifluoromethyl)phenyl]methanone
Homo sapiens
IC50 above 0.01 mM, at pH 7.4, temperature not specified in the publication
0.00046
(6-azaspiro[3.5]nonan-6-yl)(2,4-dichloro-6-hydroxyphenyl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.000083
2-(6-azaspiro[3.4]octane-6-sulfonyl)-3,5-dichlorophenol
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00003
2-(6-azaspiro[3.4]octane-6-sulfonyl)-3,5-difluorophenol
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.01
2-(6-azaspiro[3.4]octane-6-sulfonyl)-3-fluorophenol
Homo sapiens
IC50 above 0.01 mM, at pH 7.4, temperature not specified in the publication
0.00004
2-(6-azaspiro[3.4]octane-6-sulfonyl)-5-fluorophenol
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.01
4-(6-azaspiro[3.4]octane-6-carbonyl)-3-chloro-5-hydroxybenzamide
Homo sapiens
IC50 above 0.01 mM, at pH 7.4, temperature not specified in the publication
0.01
4-(6-azaspiro[3.4]octane-6-carbonyl)-3-chloro-5-hydroxybenzonitrile
Homo sapiens
IC50 above 0.01 mM, at pH 7.4, temperature not specified in the publication
0.00029
N-acetylsulfapyridine
Homo sapiens
pH and temperature not specified in the publication
0.0006
[4-(benzenesulfonyl)piperidin-1-yl](2,4-dichloro-6-hydroxyphenyl)methanone
Homo sapiens
at pH 7.4, temperature not specified in the publication
0.00012
Chlorpropamide
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.0006
N-acetylserotonin
Homo sapiens
pH and temperature not specified in the publication
0.000019
sulfamethoxazole
Homo sapiens
pH and temperature not specified in the publication
0.00018
sulfamethoxazole
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.000141
sulfapyridine
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.00048
sulfapyridine
Homo sapiens
pH and temperature not specified in the publication
0.0000235
sulfasalazine
Homo sapiens
pH and temperature not specified in the publication
0.000031
sulfasalazine
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.000014
sulfathiazole
Homo sapiens
pH and temperature not specified in the publication
0.000062
sulfathiazole
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.4
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
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
SPR mRNA expression is highest in all neuroblastoma clinical groups with poor outcome
-
sepiapterin reductase expression is increased in Parkinsons disease brain tissue
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
the enzyme plays an important role in the biosynthesis of tetrahydrobiopterin
physiological function
additional information
malfunction
RNAi-mediated knockdown of SPR expression significantly reduces native ornithine decarboxylase enzyme activity and impedes neuroblastoma cell proliferation
malfunction
the knockdown of SPR leads to a significant and consistent decrease in cellular proliferation of neuroblastoma cells
physiological function
high SPR expression is significantly correlated to unfavorable neuroblastoma characteristics like high age at diagnosis, MYCN oncogene amplification, and high INSS disease stage. Sulfasalazine inhibits the growth of neuroblatoma cells in vitro, presumably due to the inhibition of sepiapterin reductase
physiological function
in PC12 cells, which generate catecholamine and monoamine neurotransmitters via BH4-dependent amino acid hydroxylases, sulfa drugs inhibit both dihydrobiopterin/tetrahydrobiopterin biosynthesis and redox cycling mediated by sepiapterin reductase. Inhibition of dihydrobiopterin/tetrahydrobiopterin biosynthesis results in decreased production of dopamine and dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, and 5-hydroxytryptamine
physiological function
native ornithine decarboxylase and sepiapterin reductase physically interact. The resulting heterocomplex is a compact structure, featuring two energetically and structurally equivalent binding modes both in monomer and dimer conformations. siRNA-mediated knock-down of sepiapterin reductase expression significantly reduces endogenous ornithine decarboxylase enzyme activity in neuroblastoma cells
physiological function
sepiapterin reductase (SPR) catalyzes the last step in the biosynthesis of tetrahydrobiopterin (BH4) by converting 6-pyruvoyl tetrahydropterin to tetrahydrobiopterin. BH4 is an essential cofactor of nitric oxide synthase (NOS), which converts arginine to nitric oxide (NO) and citrulline in the urea cycle. Native ornithine decarboxylase, ODC, EC 4.1.1.17, and sepiapterin reductase physically interact, SPR is a regulator of ODC activity. SPR is implicated in neurological diseases and in cancer. SPR contributes to neuroblastoma cell proliferation and regulates ODC enzyme activity in neuroblastoma cells, ODC-SPR interaction controls polyamine-driven cellular proliferation
physiological function
using NADPH as a source of reducing equivalents, sepiapterin reductase (SPR) catalyzes the reduction of sepiapterin to dihydrobiopterin (BH2), a precursor for tetrahydrobiopterin (BH4). Reduction of sepiapterin generates 7,8-dihydrobiopterin, which is converted to (6R)-5,6,7,8-tetrahydrobiopterin by additional cellular reductases
additional information
computational docking of inhibitor sulfasalazine into sepiapterin reductase using crystal structure of human SPR in complex with NADP+ in a hexameric assembly, PDB ID 1Z6Z
additional information
-
computational docking of inhibitor sulfasalazine into sepiapterin reductase using crystal structure of human SPR in complex with NADP+ in a hexameric assembly, PDB ID 1Z6Z
additional information
enzyme three-dimensional structure molecular modeling and docking using crystal structures of SPR, PDB IDs 1SEP, 1NAS, 4HWK, 4J7U, and 4J7X, and the structure of menadione, PDB ID 2QR2, overview
additional information
-
enzyme three-dimensional structure molecular modeling and docking using crystal structures of SPR, PDB IDs 1SEP, 1NAS, 4HWK, 4J7U, and 4J7X, and the structure of menadione, PDB ID 2QR2, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). SPRE_HUMAN
261
0
28048
Swiss-Prot
Mitochondrion (Reliability: 5)
Q9UEC5_HUMAN
62
0
7009
TrEMBL
other Location (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
28000
28000
-
2 * 28000, SDS-PAGE, Western blot analysis with polyclonal rabbit-antiserum, determined by cDNA sequence
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
the SPR monomer is an alpha and beta (a/b) class protein with a 3-layer (aba) sandwich architecture and Rossmann fold topology, and it contains an NADP-binding Rossmann-like domain
homodimer
additional information
homodimer
-
2 * 28000, SDS-PAGE, Western blot analysis with polyclonal rabbit-antiserum, determined by cDNA sequence
additional information
in silico protein-protein docking simulationsof enzyme SPR with ornithine decraboxylase, ODC, structure analysis, overview
additional information
-
in silico protein-protein docking simulationsof enzyme SPR with ornithine decraboxylase, ODC, structure analysis, overview
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
silico protein-protein docking simulations to define the individual amino acid residues involved in the interaction between native ornithine decarboxylase and sepiapterin reductase
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D257H
-
mutant shows completely inhibited sepiapterin reduction. Mutation has only minimal effects on redox cycling
DELTA257-261
-
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
-
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
-
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
-
naturally occurring mutation in gene SPR, exon 3, causing enzyme deficiency
M205G
-
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
-
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
-
naturally occurring mutation in gene SPR, exon 2, causing enzyme deficiency
Q119X
-
naturally occurring mutation in gene SPR, exon 2, causing enzyme deficiency
R150fs
-
naturally occurring mutation in gene SPR, exon 2, causing enzyme deficiency
R150G
-
naturally occurring mutation in gene SPR, exon 2, causing enzyme deficiency
R42G
-
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
-
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
-
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
additional information
additional information
-
identification of different mutant alleles or molecular lesions of enzymes, involved in the tetrahydrobiopterin metabolism, leading to disorders, SPR deficiency causes an autosomal recessive monoamine neurotransmitter deficiency, mutations occur in exons 2 and 3, in intron 2, and in the 5'-UTR, overview
additional information
-
a single nucleotide polymorphism around the SPR gene is involved in development of Parkonson's disease
additional information
siRNA-mediated knockdown of SPR expression, significantly reduces endogenous ornithine decarboxylase enzyme activity in neuroblastoma cells and leads to a significant and consistent decrease in cellular proliferation
additional information
-
siRNA-mediated knockdown of SPR expression, significantly reduces endogenous ornithine decarboxylase enzyme activity in neuroblastoma cells and leads to a significant and consistent decrease in cellular proliferation
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene SPR, chromosomal location at 2p13, genomic structure, DNA and amino acid sequence determination of wild-type and mutant enzymes
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the enzyme mRNA level increases in the brains of Parkinson's disease patients
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
polymorphisms of sepiapterin reductase gene alter promoter activity and may influence risk of bipolar disorder
medicine
high sepiapterin reductase expression is significantly correlated to unfavorable neuroblastoma characteristics like high age at diagnosis, MYCN amplification, and high INSS stage. Sulfasalazine inhibits the growth of neuroblastoma cells in vitro, presumably due to the inhibition of sepiapterin reductase. The combination of sulfasalazine with alpha-difluoromethylornitine produces synergistic antiproliferative effects in vitro
medicine
siRNA-mediated knock-down of sepiapterin reductase expression significantly reduces endogenous ornithine decarboxylase enzyme activity in neuroblastoma cells. In a cohort of 88 human neuroblastoma tumors, high SPR mRNA expression correlates significantly with poor survival prognosis
medicine
the enzyme can regulate chronic pain and is a target for the development of analgesics
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Fere, J.; Naylor, E.W.
Sepiapterin reductase in cultured human cells
Biochem. Biophys. Res. Commun.
148
1475-1481
1987
Homo sapiens
Werner, E.R.; Werner-Felmayer, G.; Fuchs, D.; Hausen, A.; Reibnegger, G.; Yim, J.J.; Pfleiderer, W.; Wachter, H.
Tetrahydrobiopterin biosynthetic activities in human macrophages, fibroblasts, THP-1, and T 24 cells. GTP-cyclohydrolase I is stimulated by interferon-gamma, and 6-pyruvoyl tetrahydropterin synthase and sepiapterin reductase are constitutively present
J. Biol. Chem.
265
3189-3192
1990
Drosophila melanogaster, Drosophila melanogaster Oregon R, Homo sapiens
Curtius, H.C.; Heintel, D.; Ghisla, S.; Kuster, T.; Leimbacher, W.; Niederwieser, A.
Tetrahydrobiopterin biosynthesis. Studies with specifically labeled (2H)NAD(P)H and 2H2O and of the enzymes involved
Eur. J. Biochem.
148
413-419
1985
Homo sapiens
Maier, J.; Ziegler, I.
Purification and properties of human sepiapterin reductase from placenta
Adv. Exp. Med. Biol.
338
199-202
1993
Homo sapiens
Ikemoto, K.; Suzuki, T.; Ichinose, H.; Ohye, T.; Nishimura, A.; Nishi, K.; Nagatsu, I.; Nagatsu, T.
Localization of sepiapterin reductase in the human brain
Brain Res.
954
237-246
2002
Homo sapiens, Mus musculus
Thoeny, B.; Blau, N.
Mutations in the BH4-metabolizing genes GTP cyclohydrolase I, 6-pyruvoyl-tetrahydropterin synthase, sepiapterin reductase, carbinolamine-4a-dehydratase, and dihydropteridine reductase
Hum. Mutat.
27
870-878
2006
Homo sapiens
Tobin, J.E.; Cui, J.; Wilk, J.B.; Latourelle, J.C.; Laramie, J.M.; McKee, A.C.; Guttman, M.; Karamohamed, S.; DeStefano, A.L.; Myers, R.H.
Sepiapterin reductase expression is increased in Parkinsons disease brain tissue
Brain Res.
1139
42-47
2007
Homo sapiens
Widder, J.D.; Chen, W.; Li, L.; Dikalov, S.; Thoeny, B.; Hatakeyama, K.; Harrison, D.G.
Regulation of tetrahydrobiopterin biosynthesis by shear stress
Circ. Res.
101
830-838
2007
Homo sapiens
Sawabe, K.; Yamamoto, K.; Harada, Y.; Ohashi, A.; Sugawara, Y.; Matsuoka, H.; Hasegawa, H.
Cellular uptake of sepiapterin and push-pull accumulation of tetrahydrobiopterin
Mol. Genet. Metab.
94
410-416
2008
Homo sapiens
Hirakawa, H.; Sawada, H.; Yamahama, Y.; Takikawa, S.; Shintaku, H.; Hara, A.; Mase, K.; Kondo, T.; Iino, T.
Expression analysis of the aldo-keto reductases involved in the novel biosynthetic pathway of tetrahydrobiopterin in human and mouse tissues
J. Biochem.
146
51-60
2009
Homo sapiens, Mus musculus
McHugh, P.C.; Joyce, P.R.; Kennedy, M.R.
Polymorphisms of sepiapterin reductase gene alter promoter activity and may influence risk of bipolar disorder
Pharmacogenet. Genomics
19
330-337
2009
Homo sapiens
Yang, S.; Jan, Y.H.; Gray, J.P.; Mishin, V.; Heck, D.E.; Laskin, D.L.; Laskin, J.D.
Sepiapterin Reductase Mediates Chemical Redox Cycling in Lung Epithelial Cells
J. Biol. Chem.
288
19221-19237
2013
Homo sapiens
Lange, I.; Geerts, D.; Feith, D.J.; Mocz, G.; Koster, J.; Bachmann, A.S.
Novel interaction of ornithine decarboxylase with sepiapterin reductase regulates neuroblastoma cell proliferation
J. Mol. Biol.
426
332-346
2014
Homo sapiens (P35270), Homo sapiens
Yco, L.; Geerts, D.; Mocz, G.; Koster, J.; Bachmann, A.
Effect of sulfasalazine on human neuroblastoma: Analysis of sepiapterin reductase (SPR) as a new therapeutic target
BMC Cancer
15
477
2015
Homo sapiens (P35270), Homo sapiens
Yang, S.; Jan, Y.H.; Mishin, V.; Richardson, J.R.; Hossain, M.M.; Heindel, N.D.; Heck, D.E.; Laskin, D.L.; Laskin, J.D.
Sulfa drugs inhibit sepiapterin reduction and chemical redox cycling by sepiapterin reductase
J. Pharmacol. Exp. Ther.
352
529-540
2015
Rattus norvegicus (P18297), Homo sapiens (P35270), Homo sapiens
Gao, H.; Schneider, S.; Andrews, P.; Wang, K.; Huang, X.; Sparling, B.A.
Virtual screening to identify potent sepiapterin reductase inhibitors
Bioorg. Med. Chem. Lett.
30
126793
2020
Homo sapiens (P35270)
Wu, Y.; Chen, P.; Sun, L.; Yuan, S.; Cheng, Z.; Lu, L.; Du, H.; Zhan, M.
Sepiapterin reductase Characteristics and role in diseases
J. Cell. Mol. Med.
24
9495-9506
2020
Homo sapiens (P35270)
EXTERNAL LINKS (specific for EC-Number 1.1.1.153)
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Release 2023.1 (January 2023)
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