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Information on EC 1.1.1.153 - sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)
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EC Tree
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 expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Synonyms
akr1b1, sepiapterin reductase, mdspr, mdspi16 protein, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
reductase, sepiapterin
-
-
-
-
sepiapterin reductase
SPR
SR
SPR
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
L-erythro-tetrahydrobiopterin + 2 NADP+ = 6-pyruvoyl-5,6,7,8-tetrahydropterin + 2 NADPH + 2 H+
-
-
-
-
L-erythro-7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH + H+
ordered bi-bi mechanism, NADPH binds first and NADP+ releases last
-
L-erythro-7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH + H+
enzyme also reduces carbonyl compounds of non-pteridine derivatives
-
L-erythro-7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH + H+
enzyme also reduces carbonyl compounds of non-pteridine derivatives
-
L-erythro-7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH + H+
enzyme also reduces carbonyl compounds of non-pteridine derivatives
-
L-erythro-7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH + H+
active site structure
-
L-erythro-7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH + H+
active site structure, substrate binding mode for stereospecific production of L-threo-tetrahydrobiopterin, stereospecific hydride transfer, mechanism, structure-function relationship, overview
-
L-erythro-7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH + H+
enzyme also reduces carbonyl compounds of non-pteridine derivatives
-
-
L-erythro-7,8-dihydrobiopterin + NADP+ = sepiapterin + NADPH + H+
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
KEGG
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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).
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CAS REGISTRY NUMBER
COMMENTARY
9059-48-7
-
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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'-hydroxy-2'-oxopropyltetrahydropterin + NADP+
L-erythro-tetrahydrobiopterin + NADPH
-
-
-
?
1'-hydroxy-2'-oxopropyltetrahydropterin + NADPH
L-erythrotetrahydrobiopterin + NADP+
-
-
-
-
?
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+
L-threo-(6R,1'S,2'S)-5,6,7,8-tetrahydrobiopterin + NADP+
6-pyruvoyl tetrahydropterin + NADPH + H+
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
6-pyruvoyltetrahydropterin + NADPH
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
-
-
no synthesis of the D-isomer
-
?
diacetyl + NADPH
acetoin + NADP+
-
NADPH-dependent dicarbonyl reductase activity
-
-
?
isosepiapterin + NADPH
6-(1-hydroxypropyl)-dihydropterin + NADP+
-
-
-
?
L-threo-dihydrobiopterin + NADP+
?
-
D-isomer 45% relative activity
-
-
r
lactoyltetrahydropterin + NADPH
L-erythrotetrahydrobiopterin + NADP+
-
-
-
-
?
lactoyltetrahydropterin + NADPH + H+
L-erythro-tetrahydrobiopterin + NADP+
-
-
-
?
phenylpropanedione + NADPH
phenylpropan-2,3-diol + NADP+
-
NADPH-dependent dicarbonyl reductase activity
-
-
?
pyruvoyltetrahydropterin + NADPH
L-erythrotetrahydrobiopterin + NADP+
-
-
-
-
?
xanthopterin B2 + NADPH
6-(1',2'-dihydroxypropyl)-dihydrolumazine + NADP+
-
-
-
?
1'-oxo-2'-D-hydroxypropyl-tetrahydropterin + NADP+
D-sepiapterin + NADPH
-
-
i.e. 1'-oxo-2'-D-hydroxypropyl-dihydropterin
-
?
1'-oxo-2'-D-hydroxypropyl-tetrahydropterin + NADP+
D-sepiapterin + NADPH
-
-
i.e. 1'-oxo-2'-D-hydroxypropyl-dihydropterin
-
?
1'-oxo-2'-D-hydroxypropyl-tetrahydropterin + NADPH
tetrahydrodictyopterin + NADP+
-
-
-
-
?
1'-oxo-2'-D-hydroxypropyl-tetrahydropterin + NADPH
tetrahydrodictyopterin + NADP+
-
preferred substrate
-
-
?
1'-oxo-2'-D-hydroxypropyl-tetrahydropterin + NADPH
tetrahydrodictyopterin + NADP+
-
-
-
-
?
1'-oxo-2'-D-hydroxypropyl-tetrahydropterin + NADPH
tetrahydrodictyopterin + NADP+
-
preferred substrate
-
-
?
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
L-sepiapterin + NADPH
-
-
i.e. 1'-oxo-2'-L-hydroxypropyl-dihydropterin
-
?
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
L-sepiapterin + NADPH
-
-
i.e. 1'-oxo-2'-L-hydroxypropyl-dihydropterin
-
?
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADPH
L-erythro-tetrahydrobiopterin + NADP+
-
-
-
-
?
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADPH
L-erythro-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+
-
-
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
-
-
r
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+
-
-
-
?
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+
-
in the reverse reaction, L-erythro and L-threo-dihydroneopterin are also oxidized, the corresponding L-isomers are inactive
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
equilibrium lies much in favor of dihydrobiopterin formation
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
reverse reaction, L-erythro and L-threo-dihydroneopterin are also oxidized, the corresponding D-isomers are inactive
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
-
-
r
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-(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+
-
-
-
r
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+
-
-
-
r
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+
-
-
-
?
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+
-
-
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
in the reverse reaction, L-erythro and L-threo-dihydroneopterin are also oxidized, the corresponding L-isomers are inactive
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
equilibrium lies much in favor of dihydrobiopterin formation
-
?
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
equilibrium lies much in favor of dihydrobiopterin formation
-
r
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-(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+
-
reverse reaction, L-erythro and L-threo-dihydroneopterin are also oxidized, the corresponding D-isomers are inactive
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
catalyzes the complete reduction of pyrovoyltetrahydropterin to tetrahydrobiopterin
-
?
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
-
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
-
-
r
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+
-
-
-
r
6-pyruvoyl tetrahydropterin + 2 NADPH + 2 H+
L-threo-(6R,1'S,2'S)-5,6,7,8-tetrahydrobiopterin + NADP+
-
-
-
-
?
6-pyruvoyl tetrahydropterin + 2 NADPH + 2 H+
L-threo-(6R,1'S,2'S)-5,6,7,8-tetrahydrobiopterin + NADP+
-
last step of the de novo tetrahydrobiopterin biosynthesis initiating from GTP
-
-
?
6-pyruvoyl tetrahydropterin + 2 NADPH + 2 H+
L-threo-(6R,1'S,2'S)-5,6,7,8-tetrahydrobiopterin + NADP+
-
last step of the tetrahydrobiopterin biosynthesis
-
-
?
6-pyruvoyl tetrahydropterin + 2 NADPH + 2 H+
L-threo-(6R,1'S,2'S)-5,6,7,8-tetrahydrobiopterin + NADP+
-
substrate binding mode for stereospecific production of L-threo-tetrahydrobiopterin, structure-function relationship
-
-
?
6-pyruvoyl tetrahydropterin + 2 NADPH + 2 H+
L-threo-(6R,1'S,2'S)-5,6,7,8-tetrahydrobiopterin + NADP+
-
two reductive steps oxidizing NADPH
-
-
?
6-pyruvoyl tetrahydropterin + 2 NADPH + 2 H+
tetrahydrobiopterin + NADP+
-
-
-
-
?
6-pyruvoyl tetrahydropterin + 2 NADPH + 2 H+
tetrahydrobiopterin + NADP+
-
final step in the synthesis of tetrahydrobiopterin, role in detoxification of exogenous carbonyl compounds suggested
-
-
?
6-pyruvoyl tetrahydropterin + NADPH + H+
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
-
-
-
-
?
6-pyruvoyl tetrahydropterin + NADPH + H+
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
-
1'-oxo-2'-D-hydroxypropyl-tetrahydropterin is formed by an aldose reductase-like enzyme activity, not by SR
-
-
?
6-pyruvoyl tetrahydropterin + NADPH + H+
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
-
-
-
-
?
6-pyruvoyl tetrahydropterin + NADPH + H+
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
-
-
-
-
?
6-pyruvoyl-5,6,7,8-tetrahydropterin + NADPH
tetrahydrobiopterin + NADP+
-
-
-
-
r
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
6-pyruvoyl-5,6,7,8-tetrahydropterin + NADPH
tetrahydrobiopterin + NADP+
-
-
-
-
r
6-pyruvoyltetrahydropterin + 2 NADPH + 2 H+
L-erythro-tetrahydrobiopterin + 2 NADP+
-
-
-
?
6-pyruvoyltetrahydropterin + 2 NADPH + 2 H+
L-erythro-tetrahydrobiopterin + 2 NADP+
-
-
-
?
6-pyruvoyltetrahydropterin + 2 NADPH + 2 H+
L-erythro-tetrahydrobiopterin + 2 NADP+
-
-
-
-
?
6-pyruvoyltetrahydropterin + 2 NADPH + 2 H+
L-threo-tetrahydrobiopterin + 2 NADP+
-
-
no formation of the L-erythro isomer
-
?
6-pyruvoyltetrahydropterin + 2 NADPH + 2 H+
L-threo-tetrahydrobiopterin + 2 NADP+
-
final step in the synthesis of tetrahydrobiopterin
no formation of the L-erythro isomer
-
?
6-pyruvoyltetrahydropterin + 2 NADPH + 2 H+
L-threo-tetrahydrobiopterin + 2 NADP+
-
no formation of the L-erythro isomer
-
?
6-pyruvoyltetrahydropterin + 2 NADPH + 2 H+
L-threo-tetrahydrobiopterin + 2 NADP+
final step in the synthesis of tetrahydrobiopterin
no formation of the L-erythro isomer
-
?
L-erythro-dihydroneopterin + NADP+
?
-
very slow activity, no activity with the D-isomer
-
-
r
L-threo-dihydroneopterin + NADP+
?
-
very slow activity, no activity with the D-isomer
-
-
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+
7,8-dihydrobiopterin + NADP+
-
-
detailed product determination and analysis using fluorescent substrates, 7,8-dihydrobiopterin can be oxidized nonenzymatically to biopterin
-
?
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
-
i.e. 2-amino-4-hydroxy-6-lactyl-7,8-dihydropteridine, biosynthesis pathway, overview
i.e. 2-amino-4-hydroxy-6-(1',2'-dihydroxypropyl-)7,8-dihydropteridine, which is a substrate for biosynthesis of tetrahydrobiopterin, i.e. 6R-L-erythro-1',2'-dihydroxy-propyl-2-amino-4-hydroxy-5,6,7,8-tetrahydropteridine, an important component for controling the concentration of catecholamines or indoleamines in the brain and other nerve tissues
-
?
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
-
sepiapterin reductase activity
-
-
?
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
no stereochemic specification in the publication
-
-
?
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
-
-
-
-
?
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
-
?
sepiapterin + NADPH + H+
tetrahydrobiopterin + NADP+
-
no stereochemic specification in the publication
-
?
additional information
?
-
-
D-threo-tetrahydrobiopterin is synthesized via 1'-oxo-2'-D-hydroxypropyl-tetrahydropterin in Dictyostelium discoideum strain Ax2
-
-
?
additional information
?
-
-
quantitative in vivo assay and product determination
-
-
?
additional information
?
-
-
tetrahydropteridines in Dictyostelium are associated with mitochondrial function, probably via direct protection against oxidative stress, tetrahydropteridine deficiency impairs mitochondrial function in Dictyostelium discoideum Ax2
-
-
?
additional information
?
-
-
the enzyme catalyzes the final step in the tetrahydrobiopterin biosynthesis
-
-
?
additional information
?
-
-
quantitative in vivo assay and product determination
-
-
?
additional information
?
-
-
D-threo-tetrahydrobiopterin is synthesized via 1'-oxo-2'-D-hydroxypropyl-tetrahydropterin in Dictyostelium discoideum strain Ax2
-
-
?
additional information
?
-
-
no activity with 6-acetyl-7-methyl-7,8-dihydropterin
-
-
?
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
-
-
?
additional information
?
-
-
final step in the synthesis of tetrahydrobiopterin
-
-
?
additional information
?
-
-
important in the metabolism of tetrahydrobiopterin and sepiapterin
-
-
?
additional information
?
-
-
enzyme is quite similar to general aldo-keto reductases, especially to carbonyl reductase
-
-
?
additional information
?
-
-
some monoketotestosterones show slight activity
-
-
?
additional information
?
-
-
enzyme also catalyzes the isomerization of 6-1'-oxo-2'-hydroxypropyl tetrahydropterin (6-lactoyltetrahydropterin) to 6-1'-hydroxy-2'-oxopropyltetrahydropterin
-
-
?
additional information
?
-
-
final step in the synthesis of tetrahydrobiopterin
-
-
?
additional information
?
-
-
the enzyme might be involved in regulation of biosynthesis of catecholamines, indoleamines, and tetrahydrobiopterins
-
-
?
additional information
?
-
-
descending substrate preference: sepiapterin, lactoyltetrahydropterin, pyruvoyltetrahydropterin, 1'-hydroxy-2'-oxopropyltetrahydropterin
-
-
?
additional information
?
-
-
substrate specificity, the enzyme also exhibits non-specific NADPH-dependent dicarbonyl reductase activity, 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
-
-
?
additional information
?
-
-
the enzyme might be involved in regulation of biosynthesis of catecholamines, indoleamines, and tetrahydrobiopterins
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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-pyruvoyl tetrahydropterin + 2 NADPH + 2 H+
L-threo-(6R,1'S,2'S)-5,6,7,8-tetrahydrobiopterin + NADP+
6-pyruvoyl tetrahydropterin + 2 NADPH + 2 H+
tetrahydrobiopterin + NADP+
-
final step in the synthesis of tetrahydrobiopterin, role in detoxification of exogenous carbonyl compounds suggested
-
-
?
6-pyruvoyl tetrahydropterin + NADPH + H+
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
-
-
-
-
?
6-pyruvoyltetrahydropterin + NADPH
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
-
-
no synthesis of the D-isomer
-
?
1'-oxo-2'-D-hydroxypropyl-tetrahydropterin + NADP+
D-sepiapterin + NADPH
-
-
-
-
?
1'-oxo-2'-D-hydroxypropyl-tetrahydropterin + NADP+
D-sepiapterin + NADPH
-
-
-
-
?
1'-oxo-2'-D-hydroxypropyl-tetrahydropterin + NADPH
tetrahydrodictyopterin + NADP+
-
-
-
-
?
1'-oxo-2'-D-hydroxypropyl-tetrahydropterin + NADPH
tetrahydrodictyopterin + NADP+
-
-
-
-
?
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
L-sepiapterin + NADPH
-
-
-
-
?
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
L-sepiapterin + NADPH
-
-
-
-
?
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADPH
L-erythro-tetrahydrobiopterin + NADP+
-
-
-
-
?
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADPH
L-erythro-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+
-
-
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
-
-
r
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+
-
-
-
?
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+
-
equilibrium lies much in favor of dihydrobiopterin formation
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
reverse reaction, L-erythro and L-threo-dihydroneopterin are also oxidized, the corresponding D-isomers are inactive
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
-
-
r
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-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
-
-
r
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+
-
-
-
r
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+
-
-
-
?
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+
-
-
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
equilibrium lies much in favor of dihydrobiopterin formation
-
?
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
equilibrium lies much in favor of dihydrobiopterin formation
-
r
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-(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+
-
reverse reaction, L-erythro and L-threo-dihydroneopterin are also oxidized, the corresponding D-isomers are inactive
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
catalyzes the complete reduction of pyrovoyltetrahydropterin to tetrahydrobiopterin
-
?
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
-
-
r
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
-
-
-
r
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+
-
-
-
r
6-pyruvoyl tetrahydropterin + 2 NADPH + 2 H+
L-threo-(6R,1'S,2'S)-5,6,7,8-tetrahydrobiopterin + NADP+
-
last step of the de novo tetrahydrobiopterin biosynthesis initiating from GTP
-
-
?
6-pyruvoyl tetrahydropterin + 2 NADPH + 2 H+
L-threo-(6R,1'S,2'S)-5,6,7,8-tetrahydrobiopterin + NADP+
-
last step of the tetrahydrobiopterin biosynthesis
-
-
?
6-pyruvoyl-5,6,7,8-tetrahydropterin + NADPH
tetrahydrobiopterin + NADP+
-
-
-
-
r
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
6-pyruvoyl-5,6,7,8-tetrahydropterin + NADPH
tetrahydrobiopterin + NADP+
-
-
-
-
r
6-pyruvoyltetrahydropterin + 2 NADPH + 2 H+
L-threo-tetrahydrobiopterin + 2 NADP+
-
final step in the synthesis of tetrahydrobiopterin
no formation of the L-erythro isomer
-
?
6-pyruvoyltetrahydropterin + 2 NADPH + 2 H+
L-threo-tetrahydrobiopterin + 2 NADP+
final step in the synthesis of tetrahydrobiopterin
no formation of the L-erythro isomer
-
?
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+
7,8-dihydrobiopterin + NADP+
-
i.e. 2-amino-4-hydroxy-6-lactyl-7,8-dihydropteridine, biosynthesis pathway, overview
i.e. 2-amino-4-hydroxy-6-(1',2'-dihydroxypropyl-)7,8-dihydropteridine, which is a substrate for biosynthesis of tetrahydrobiopterin, i.e. 6R-L-erythro-1',2'-dihydroxy-propyl-2-amino-4-hydroxy-5,6,7,8-tetrahydropteridine, an important component for controling the concentration of catecholamines or indoleamines in the brain and other nerve tissues
-
?
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
no stereochemic specification in the publication
-
-
?
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
-
-
-
-
?
sepiapterin + NADPH + H+
tetrahydrobiopterin + NADP+
-
no stereochemic specification in the publication
-
?
sepiapterin + NADPH + H+
tetrahydrobiopterin + NADP+
-
-
no stereochemic specification in the publication
-
?
additional information
?
-
-
D-threo-tetrahydrobiopterin is synthesized via 1'-oxo-2'-D-hydroxypropyl-tetrahydropterin in Dictyostelium discoideum strain Ax2
-
-
?
additional information
?
-
-
quantitative in vivo assay and product determination
-
-
?
additional information
?
-
-
tetrahydropteridines in Dictyostelium are associated with mitochondrial function, probably via direct protection against oxidative stress, tetrahydropteridine deficiency impairs mitochondrial function in Dictyostelium discoideum Ax2
-
-
?
additional information
?
-
-
quantitative in vivo assay and product determination
-
-
?
additional information
?
-
-
D-threo-tetrahydrobiopterin is synthesized via 1'-oxo-2'-D-hydroxypropyl-tetrahydropterin in Dictyostelium discoideum strain Ax2
-
-
?
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
?
-
-
final step in the synthesis of tetrahydrobiopterin
-
-
?
additional information
?
-
-
important in the metabolism of tetrahydrobiopterin and sepiapterin
-
-
?
additional information
?
-
-
final step in the synthesis of tetrahydrobiopterin
-
-
?
additional information
?
-
-
the enzyme might be involved in regulation of biosynthesis of catecholamines, indoleamines, and tetrahydrobiopterins
-
-
?
additional information
?
-
-
the enzyme might be involved in regulation of biosynthesis of catecholamines, indoleamines, and tetrahydrobiopterins
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NADPH
-
-
286010, 286011, 286012, 286013, 286014, 286015, 286019, 286020, 286021, 286023, 286024, 655225, 656958, 667296
NADPH
-
determination and analysis of the binding structure of NADPH and NADP+ to the enzyme, overview
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
-
6,7-dimethylpterin
-
0.05 mM: 46% inhibition; 46% inhibition of the reductive reaction at 0.05 mM
6-Hydroxymethylpterin
-
0.05 mM: 23% inhibition; 23% inhibition of the reductive reaction at 0.05 mM
7-(3,4-dihydroxyphenyl)-5-hydroxy-10-(2-hydroxyethyl)-2,2-dimethyl-2H,6H-benzo[1,2-b:5,4-b']dipyran-6-one
-
7-Methylpterin
-
0.05 mM: 18% inhibition; 18% inhibition of the reductive reaction at 0.05 mM
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
benzoic acid
-
0.03 mM: 40% inhibition; 40% inhibition of the reductive reaction at 0.03 mM
biopterin
-
0.05 mM: 24% inhibition; 24% inhibition of the reductive reaction at 0.05 mM
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
-
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
Leucopterin
-
0.05 mM: 21% inhibition; 21% inhibition of the reductive reaction at 0.05 mM
N-(5-fluoropyridin-2-yl)-1-[2-hydroperoxy-4-(trifluoromethyl)phenyl]isoquinoline-6-sulfonamide
-
N-acetyl-L-noradrenaline
-
weak inhibitor, N-acetyl-L-adrenaline does not bind enzyme
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
-
NADP+
-
competitive inhibition at fixed concentration with varied NADPH, noncompetitive with varied sepiapterin
Propionamide
-
0.03 mM, 14% inhibition; 14% inhibition of the reductive reaction at 0.03 mM
pterin
-
0.05 mM: 18% inhibition; 18% inhibition of the reductive reaction at 0.05 mM
[4-(benzenesulfonyl)piperidin-1-yl](2,4-dichloro-6-hydroxyphenyl)methanone
-
2,4-dinitrophenol
-
37% inhibition of the reductive reaction at 0.01 mM; slight
6-Carboxypterin
-
77% inhibition of the reductive reaction at 0.05 mM; IC50 0.014 mM, 0.05 mM: 77% inhibition
Chlorpropamide
noncompetitive; noncompetitive inhibition in sepiapterin reduction and redox cycling
dihydrobiopterin
-
non-competitive with NADPH or sepiapterin as varying substrate
glibenclamide
noncompetitive inhibition in sepiapterin reduction and redox cycling
Isosepiapterin
-
83% inhibition of the reductive reaction at 0.05 mM; IC50 0.0065 mM, 0.05 mM: 83% inhibition
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
N-acetylserotonin
-
activity is completely inhibited by the addition of 0.5 mM N-acetylserotonin
NADPH
-
product inhibition, with more than 0.1 mM, with 0.05 mM sepiapterin
propionic acid
-
43% inhibition of the reductive reaction at 0.03 mM; IC50 0.0045 mM, pH 6.5
sepiapterin
-
product inhibition, with more than 0.05 mM, with 0.1 mM NADPH
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
Tolbutamide
noncompetitive inhibition in sepiapterin reduction and redox cycling
additional information
-
Li+, Na+, Co2+, Mn2+, Ni2+ show slight inhibition at 1 mM
-
additional information
-
other unconjugated pteridines, e.g. xanthopterin, that cause slight inhibition of enzymatic reduction
-
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
-
additional information
-
no inhibition by 1-epinephrine, phenylalanine, tyrosine, L-DOPA, L-tryptophan, L-5-hydroxy-tryptophan
-
additional information
sulfonylurea- or sulfonamide-based drugs inhibit sepiapterin reduction and chemical redox cycling by sepiapterin reductase
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
the enzyme activity is not affected by laminar shear stress in endothelial cells, overview
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0283
sepiapterin
-
recombinant enzyme, in 100 mM potassium phosphate buffer (pH 6.4), at 37°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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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
0.1
Melatonin
Bombyx mori
-
recombinant enzyme, in 100 mM potassium phosphate buffer (pH 6.4), at 37°C
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
0.2
N-acetylserotonin
Bombyx mori
-
recombinant enzyme, in 100 mM potassium phosphate buffer (pH 6.4), at 37°C
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
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
1.7
-
in Escherichia coli HB101, transformed with pBLY1 containing sepiapterin reductase cDNA
additional information
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
10.4
5.5
6.4
6.8
7.4
7.8
8.6
-
optimum of isomerization of 6-1'-oxo-2'-hydroxypropyl(6-lactoyltetrahydropterin) to 6-1'-hydroxy-2'-oxopropyltetrahydropterin
10.4
-
the reverse reaction, oxidation of 7,8-dihydrobiopterin, activity rises with rise of pH
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
2.5 - 12
activity range, profile overview, recombinant His-tagged enzyme, over 50% of maximal activity at pH 3.0-11.0
3 - 6
the enzymatic activity is high under the pH range of 3.0 to 6.0
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
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
30
37
50
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
20 - 90
activity range, profile overview, recombinant His-tagged enzyme, over 50% of maximal activity at 30-85°C
40 - 70
the enzymatic activity is high under the temperature range of 40 to 70°C
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
brenda
-
-
-
brenda
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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
brenda
SPR mRNA expression is highest in all neuroblastoma clinical groups with poor outcome
brenda
additional information
-
sepiapterin reductase expression is increased in Parkinsons disease brain tissue
brenda
-
-
brenda
additional information
-
not in leukocytes and ascites tumor cells
brenda
additional information
-
SR gene expression and activity in different developmental stages
brenda
additional information
-
SR gene expression and activity in different developmental stages
-
brenda
additional information
during the development of Musca domestica, the expression of MDSPR in the larvae is higher than other developmental stages
brenda
additional information
-
during the development of Musca domestica, the expression of MDSPR in the larvae is higher than other developmental stages
brenda
additional information
-
not in leukocytes and ascites tumor cells
brenda
additional information
-
tissue distribution, no activity in stomach, small intestine, and muscle, overview
brenda
additional information
-
not in leukocytes and ascites tumor cells
-
brenda
additional information
-
not in leukocytes and ascites tumor cells
-
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
additional information
malfunction
RNAi-mediated knockdown of SPR expression significantly reduces native ornithine decarboxylase enzyme activity and impedes neuroblastoma cell proliferation
malfunction
-
tetrahydrobiopterin deficiencies are implicated in neuronal disorders. Drosophile melanogastersloss-of-function enzyme mutants are resonsibel for hyposensitivityy to oxidative stress, enzyme activity and tetrahydrobiopterin levels in the mutants are significantly reduced compared to wild-type, while levels of phosphorylated Akt and total Akt protein are increased in the enzyme mutants
malfunction
the knockdown of SPR leads to a significant and consistent decrease in cellular proliferation of neuroblastoma cells
malfunction
enzyme inhibition reduces pain hypersensitivity in a mouse model of joint inflammation
metabolism
sepiapterin reductase (SPR) catalyzes the final steps of tetrahydrobiopterin (BH4) biosynthesis
metabolism
-
sepiapterin reductase is a key enzyme in the biosynthesis of tetrahydrobiopterin (BH4), an essential cofactor for the synthesis of important biogenic amines, including catecholamines and serotonin
metabolism
the enzyme plays an important role in the biosynthesis of tetrahydrobiopterin
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 final steps of tetrahydrobiopterin (BH4) biosynthesis. BH4 is an essential cofactor for aromatic acid hydroxylases and nitric oxide synthase. BH4 deficiency causes endothelial dysfunction, such as hypertension, atherosclerosis, diabetes, etc.
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
-
sepiapterin reductase plays an important role in the Akt pathway
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
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
Show AA Sequence and Transmembrane Helices (1091 entries)
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
28000
30000
55000
56000
28000
-
2 * 28000, SDS-PAGE, Western blot analysis with polyclonal rabbit-antiserum, determined by cDNA sequence
30000
-
x * 30000, Western blot analysis of native enzyme from crude cell extract
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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
monomer
additional information
?
-
x * 30000, Western blot analysis of native enzyme from crude cell extract
homodimer
-
2 * 28000, SDS-PAGE, Western blot analysis with polyclonal rabbit-antiserum, determined by cDNA sequence
additional information
-
structure-function relationship, amino acid sequence comparison of several species
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
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified native and selenomethionine-labeled enzyme alone and in complex with NADP+ and sepiapterin, hanging drop vapour diffusion method, 18°C, 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
-
purified native and selenomethionine-labeled enzyme, hanging drop vapour diffusion microbatch method, 18°C, 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
-
silico protein-protein docking simulations to define the individual amino acid residues involved in the interaction between native ornithine decarboxylase and sepiapterin reductase
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
F99A
-
the mutant shows 3.9fold higher Km and lower Vmax (8.95%) than the wild type enzyme
W196A
-
the mutant shows 8.7fold higher Km and lower Vmax (5.64%) than the wild type enzyme
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
K175I
-
decreased activity against a pteridine substrate and exogenous carbonyl compound
S158D
-
decreased activity against a pteridine substrate and exogenous carbonyl compound
S158D/Y171V
-
double-point mutant does not show any activity towards any substrate
Y171V
-
decreased activity against a pteridine substrate and exogenous carbonyl compound
additional information
additional information
-
construction of insertion mutants, the gene disruption leads to complete loss of enzyme activity
additional information
-
construction of a mutant disrupted in the gene encoding sepiapterin reductase, the SR mutant produces about 3% of tetrahydropteridines compared to the wild-type and shows several functional defects related to mitochondria and oxidative stress, as retarded growth, poor spore viability, impaired mitochondrial function, and increased susceptibility to oxidative stress induced by hydroxylamine or cumene-hydroperoxide, overview. The physiological defects are almost completely rescued by extrachromosomal expression of the endogenous enzyme
additional information
-
construction of insertion mutants, the gene disruption leads to complete loss of enzyme activity
-
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
additional information
-
construction of enzyme knockout mice, the SPR null mice show partial lethality and highly reduced tetrahydrobiopterin content, e.g. less than 10% of wild-type levels in the brain, and monoamine contents. Spr-null mice exhibit severe monoamine deficiencies and a tremor-like phenotype after weaning, pteridine contents in the tissues of Spr mutant mice, phenotype, overview
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25 - 50
-
relativley stable for 2 h in this range, loss of activity in 20 min at 70°C
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-15°C, in 150 mM Tris-HCl buffer, pH 6.0, second hydroxylapatite fraction, for 1 week, relatively little loss of activity
-
-15°C, purified enzyme, 0.01 M potassium phosphate buffer, pH 6.0, stable for 1 week with little loss of activity
-
-40°C, in 50 mM potassium phosphate buffer, pH 6.9, at least stable for two months
-
20°C, after ion exchange chromatography, no change in activity over one year of storage
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
liver
native enzyme 5000fold from liver by ammonium sulfate and protamine sulfate fractionation, and two times treatment by hydroxylapatite and anion exchange chromatography
-
native enzyme from erythrocytes by hydroxylapatite and NADP+-affinity chromatography, 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
-
Ni-NTA bead chromatography, MonoQ column chromatography, and Superdex 200 gel filtration
-
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3)
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
-
recombinant protein using His-tag
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
expressed in Escherichia coli BL21(DE3)/pLysS
expression of His-tagged native and selenomethionine-labeled enzyme in Escherichia coli strain BL21(DE3)
-
gene SPR, chromosomal location at 2p13, genomic structure, DNA and amino acid sequence determination of wild-type and mutant enzymes
-
host cells transfected with sense, antisense and inverse antisense oligodeoxynucleotides
-
recombinant protein expressed in Escherichia coli
site-directed mutagenesis, recombinant protein expressed in Escherichia coli GI724
-
subtractive cDNA library screening, DNA and amino acid sequence determination and analysis, sequence comparisons, phylogenetic tree, recombinant expression of His-tagged enzyme in Escherichia coli strain BL21(DE3)
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
infection with Escherichia coli induces the enzyme in Musca domestica larvae, highest after 24 h
the enzyme expression is upregulated in hepatocellular carcinoma. The enzyme expression is increased at 1 month 18fold when stabilized and is 17 and 18fold upregulated at 4 and 6 months after carcinogen treatment, respectively
the enzyme mRNA level increases in the brains of Parkinson's disease patients
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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
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Citron, B.A.; Milstien, S.; Gutierrez, J.C.; Levine, R.A.; Yanak, B.L.; Kaufman, S.
Isolation and expression of rat liver sepiapterin reductase cDNA
Proc. Natl. Acad. Sci. USA
87
6436-6440
1990
Rattus norvegicus
brenda
Nagai, M.
Studies on sepiapterin reductase: further characterization of the reaction product
Arch. Biochem. Biophys.
126
426-435
1968
Rattus norvegicus
brenda
Matsubara, M.; Katoh, S.; Akino, M.; Kaufman, S.
Sepiapterin reductase
Biochim. Biophys. Acta
122
202-212
1966
Rattus norvegicus
brenda
Katoh, S.
Sepiapterin reductase from horse liver: purification and properties of the enzyme
Arch. Biochem. Biophys.
146
202-214
1971
Equus caballus, Rattus norvegicus
brenda
Katoh, S.; Arai, Y.; Taketani, T.; Yamada, S.
Sepiapterin reductase in blood of various animals and of leukemic rats
Biochim. Biophys. Acta
370
378-388
1974
Canis lupus familiaris, Cavia porcellus, Gallus gallus, Mus musculus, Oryctolagus cuniculus, Rattus norvegicus, Rattus norvegicus Donryu, Rattus norvegicus Sprague-Dawley, Sus scrofa
brenda
Sueoka, T.; Katoh, S.
Purification and characterization of sepiapterin reductase from rat erythrocytes
Biochim. Biophys. Acta
717
265-271
1982
Rattus norvegicus
brenda
Fere, J.; Naylor, E.W.
Sepiapterin reductase in cultured human cells
Biochem. Biophys. Res. Commun.
148
1475-1481
1987
Homo sapiens
brenda
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, Homo sapiens, Drosophila melanogaster Oregon R
brenda
Kerler, F.; Hultner, L.; Ziegler, I.; Katzenmaier, G.; Bacher, A.
Analysis of the tetrahydrobiopterin synthesizing system during maturation of murine reticulocytes
J. Cell. Physiol.
142
268-271
1990
Mus musculus
brenda
Katoh, S.; Sueoka, T.
Isomerization of 6-lactoyl tetrahydropterin by sepiapterin reductase
J. Biochem.
101
275-278
1987
Rattus norvegicus
brenda
Katoh, S.; Sueoka, T.
Sepiapterin reductase exhibits a NADPH-dependent dicarbonyl reductase activity
Biochem. Biophys. Res. Commun.
118
859-866
1984
Rattus norvegicus
brenda
Sueoka, T.; Katoh, S.
Carbonyl reductase activity of sepiapterin reductase from rat erythrocytes
Biochim. Biophys. Acta
843
193-198
1985
Rattus norvegicus
brenda
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
brenda
Katoh, S.; Sueoka, T.; Yamada, S.
Direct inhibition of brain sepiapterin reductase by a catecholamine and an indoleamine
Biochem. Biophys. Res. Commun.
105
75-81
1982
Rattus norvegicus, Rattus norvegicus Sprague-Dawley
brenda
Smith, G.K.
On the role of sepiapterin reductase in the biosynthesis of tetrahydrobiopterin
Arch. Biochem. Biophys.
255
254-266
1987
Rattus norvegicus
brenda
Maier, J.; Ziegler, I.
Purification and properties of human sepiapterin reductase from placenta
Adv. Exp. Med. Biol.
338
199-202
1993
Homo sapiens
brenda
Cho, S.H.; Na, J.U.; Youn, H.; Hwang, C.S.; Lee, C.H.; Kang, S.O.
Sepiapterin reductase producing L-threo-dihydrobiopterin from Chlorobium tepidum
Biochem. J.
340
497-503
1999
Chlorobaculum tepidum
-
brenda
Smith, G.K.; Duch, D.S.; Edelstein, M.P.; Bigham, E.C.
New inhibitors of sepiapterin reductase
J. Biol. Chem.
267
5599-5607
1992
Bos taurus
brenda
Fujimoto, K.; Hara, M.; Yamada, H.; Sakurai, M.; Inaba, A.; Tomomura, A.; Katoh, S.
Role of the conserved Ser-Tyr-Lys triad of the SDR family in sepiapterin reductase
Chem. Biol. Interact.
130-132
825-832
2001
Rattus norvegicus
brenda
Ruiz-Vazquez, P.; Silva, F.J.; Ferre, J.
Characterization of sepiapterin reductase activity from Drosophila melanogaster
Comp. Biochem. Physiol. B
113
131-136
1996
Drosophila melanogaster, Drosophila melanogaster Oregon R
brenda
Kim, Y.A.; Chung, H.J.; Kim, Y.J.; Choi, Y.K.; Hwang, Y.K.; Lee, S.W.; Park, Y.S.
Characterization of recombinant Dictyostelium discoideum sepiapterin reductase expressed in E. coli
Mol. Cells
10
405-410
2000
Dictyostelium discoideum, Phycomyces sp.
brenda
Yoon, K.H.; Cha, K.W.; Park, S.I.; Yim, J.J.
Isolation and characterization of sepiapterin reductase from Drosophila melanogaster
Pteridines
4
43-50
1993
Drosophila melanogaster, Drosophila melanogaster Oregon R
-
brenda
Auerbach, G.; Herrmann, A.; Gutlich, M.; Fischer, M.; Jacob, U.; Bacher, A.; Huber, R.
The 1.25 A crystal structure of sepiapterin reductase reveals its binding mode to pterins and brain neurotransmitters
EMBO J.
16
7219-7230
1997
Mus musculus (Q64105), Mus musculus
brenda
Dowling, T.G.; O'Rourke, J.F.; Tipton, K.F.
Sepiapterin reductase and ALR2 ("aldose reductase") from bovine brain
Adv. Exp. Med. Biol.
328
313-324
1993
Bos taurus
brenda
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
brenda
Fujimoto, K.; Sakurai, M.; Kawase, M.; Katoh, S.
Effect of antisense oligodeoxynucleotide for sepiapterin reductase on the viability of PC12 cells in the presence of exogenous carbonyl compounds
Chem. Biol. Interact.
143-144
583-586
2003
Rattus norvegicus
brenda
Choi, Y.K.; Jun, S.R.; Cha, E.Y.; Park, J.S.; Park, Y.S.
Sepiapterin reductases from Chlorobium tepidum and Chlorobium limicola catalyze the synthesis of L-threo-tetrahydrobiopterin from 6-pyruvoyltetrahydropterin
FEMS Microbiol. Lett.
242
95-99
2005
Chlorobaculum tepidum, Chlorobium limicola (Q5XPX7), Chlorobium limicola
brenda
Negishi, S.; Fujimoto, K.; Katoh, S.
Localization of sepiapterin reductase in pigment cells of Oryzias latipes
Pigment Cell Res.
16
501-503
2003
Oryzias latipes, Rattus norvegicus
brenda
Supangat, S.; Choi, Y.K.; Park, Y.S.; Son, D.; Han, C.D.; Lee, K.H.
Expression, purification, crystallization and preliminary X-ray analysis of sepiapterin reductase from Chlorobium tepidum
Acta Crystallogr. Sect. F
61
202-204
2005
Chlorobaculum tepidum
brenda
Nagai, M.
Studies on sepiapterin reductase: further characterization of the reaction product
Arch. Biochem. Biophys.
126
420-435
1968
Rattus norvegicus
-
brenda
Choi, Y.K.; Kong, J.S.; Park, Y.S.
Functional role of sepiapterin reductase in the biosynthesis of tetrahydropteridines in Dictyostelium discoideum Ax2
Biochim. Biophys. Acta
1760
877-882
2006
Dictyostelium discoideum, Dictyostelium discoideum AX2
brenda
Choi, Y.K.; Park, J.S.; Kong, J.S.; Morio, T.; Park, Y.S.
D-threo-tetrahydrobiopterin is synthesized via 1-oxo-2-D-hydroxypropyl-tetrahydropterin in Dictyostelium discoideum Ax2
FEBS Lett.
579
3085-3089
2005
Dictyostelium discoideum, Dictyostelium discoideum AX2
brenda
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
brenda
Supangat, S.; Seo, K.H.; Choi, Y.K.; Park, Y.S.; Son, D.; Han, C.D.; Lee, K.H.
Structure of Chlorobium tepidum sepiapterin reductase complex reveals the novel substrate binding mode for stereospecific production of L-threo-tetrahydrobiopterin
J. Biol. Chem.
281
2249-2256
2006
Chlorobaculum tepidum
brenda
Takazawa, C.; Fujimoto, K.; Homma, D.; Sumi-Ichinose, C.; Nomura, T.; Ichinose, H.; Katoh, S.
A brain-specific decrease of the tyrosine hydroxylase protein in sepiapterin reductase-null mice - as a mouse model for Parkinsons disease
Biochem. Biophys. Res. Commun.
367
787-792
2008
Mus musculus
brenda
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
brenda
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
brenda
Kim, H.L.; Choi, Y.K.; Kim, d.o..H.; Park, S.O.; Han, J.; Park, Y.S.
Tetrahydropteridine deficiency impairs mitochondrial function in Dictyostelium discoideum Ax2
FEBS Lett.
581
5430-5434
2007
Dictyostelium discoideum
brenda
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
brenda
Supangat, S.; Park, S.O.; Seo, K.H.; Lee, S.Y.; Park, Y.S.; Lee, K.H.
Role of Phe-99 and Trp-196 of sepiapterin reductase from Chlorobium tepidum in the production of L-threo-tetrahydrobiopterin
Acta Biochim. Biophys. Sin. (Shanghai)
40
513-518
2008
Chlorobaculum tepidum
brenda
Gao, L.; Pung, Y.F.; Zhang, J.; Chen, P.; Wang, T.; Li, M.; Meza, M.; Toro, L.; Cai, H.
Sepiapterin reductase regulation of endothelial tetrahydrobiopterin and nitric oxide bioavailability
Am. J. Physiol. Heart Circ. Physiol.
297
H331-H339
2009
Bos taurus (Q17QK8), Bos taurus
brenda
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
brenda
Meng, Y.; Katsuma, S.; Daimon, T.; Banno, Y.; Uchino, K.; Sezutsu, H.; Tamura, T.; Mita, K.; Shimada, T.
The silkworm mutant lemon (lemon lethal) is a potential insect model for human sepiapterin reductase deficiency
J. Biol. Chem.
284
11698-11705
2009
Bombyx mori
brenda
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
brenda
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
brenda
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
brenda
Tang, Y.; Pei, Z.; Liu, L.; Wang, D.; Kong, L.; Liu, S.; Jiang, X.; Gao, Y.; Ma, H.
Expression and enzyme activity detection of a sepiapterin reductase gene from Musca domestica larva
Appl. Biochem. Biotechnol.
181
604-612
2016
Musca domestica (A0A172EJV6), Musca domestica
brenda
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
brenda
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
brenda
Kim, K.; Kim, H.; Yim, J.
Functional analysis of sepiapterin reductase in Drosophila melanogaster
Pteridines
26
63-68
2015
Drosophila melanogaster
-
brenda
Tang, Y.; Pei, Z.; Liu, L.; Wang, D.; Kong, L.; Liu, S.; Jiang, X.; Gao, Y.; Ma, H.
Expression and enzyme activity detection of a sepiapterin reductase gene from Musca domestica larva
Appl. Biochem. Biotechnol.
181
604-612
2017
Musca domestica (A0A172EJV6), Musca domestica
brenda
Fujita, M.; Scheffer, D.D.L.; Turnes, B.L.; Cronin, S.J.F.; Latremoliere, A.; Costigan, M.; Woolf, C.J.; Latini, A.; Andrews, N.A.
Sepiapterin reductase inhibition selectively reduces inflammatory joint pain and increases urinary sepiapterin
Arthritis Rheumatol.
72
57-66
2020
Mus musculus (Q64105), Mus musculus
brenda
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)
brenda
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)
brenda
Alen, J.; Schade, M.; Wagener, M.; Christian, F.; Nordhoff, S.; Merla, B.; Dunkern, T.R.; Bahrenberg, G.; Ratcliffe, P.
Fragment-based discovery of novel potent sepiapterin reductase inhibitors
J. Med. Chem.
62
6391-6397
2019
Homo sapiens (P35270), Homo sapiens
brenda
Ranjpour, M.; Wajid, S.; Jain, S.K.
Elevated expression of sepiapterin reductase, regulator of G protein signaling 1, hypothetical protein CXorf58 homolog, and zinc finger and BTB domain-containing protein 21 isoform X2 is associated with progression of hepatocellular carcinoma
Protoplasma
258
1133-1143
2021
Rattus norvegicus (P18297)
brenda
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