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Enzyme Nomenclature
Information on EC 1.1.1.153 - sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)
for references in articles please use BRENDA:EC1.1.1.153
Word Map on EC 1.1.1.153
- 1.1.1.153
- tetrahydrobiopterin
- bh4
-
cyclohydrolase
- aldose
-
aldo-keto
- dystonia
- tetrahydropterins
- n-acetylserotonin
- pterins
- 6-pyruvoyl-tetrahydropterin
- dihydropteridine
-
dopa-responsive
- pteridine
- neopterin
-
gtp-cyclohydrolase
-
6-pyruvoyl
- dihydroneopterin
- akr1a1s
- gtpch
- 5-hydroxytryptophan
- 2,4-diamino-6-hydroxypyrimidine
- akr1b3
-
segawa
- hyperphenylalaninaemia
- 6r-5,6,7,8-tetrahydrobiopterin
- medicine
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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
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EC NUMBER 
COMMENTARY 
1.1.1.153
-
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RECOMMENDED NAME
GeneOntology No.
sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)
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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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-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
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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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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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-
-
-
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
additional information
malfunction
-
the knockdown of SPR leads to a significant and consistent decrease in cellular proliferation of neuroblastoma cells
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
metabolism
sepiapterin reductase (SPR) catalyzes the final steps of tetrahydrobiopterin (BH4) biosynthesis
metabolism
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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
physiological function
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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; 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 (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
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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
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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; 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
physiological function
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sepiapterin reductase plays an important role in the Akt pathway
additional information
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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
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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
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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+
-
-
-
-
?
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
6-pyruvoyl tetrahydropterin + NADPH
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-pyruvoyl tetrahydropterin + NADPH + H+
L-threo-(6R,1'S,2'S)-5,6,7,8-tetrahydrobiopterin + 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+
-
-
-
-
?
sepiapterin + NADPH
1'-hydroxy-2'-oxopropyltetrahydropterin + NADP+
-
best substrate
-
-
?
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
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-
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
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?
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+
-
-
-
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-(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 + NADPH
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
-
-
-
-
?
6-pyruvoyl tetrahydropterin + NADPH
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
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 + NADPH
L-threo-(6R,1'S,2'S)-5,6,7,8-tetrahydrobiopterin + NADP+
-
last step of the tetrahydrobiopterin biosynthesis
-
-
?
6-pyruvoyl tetrahydropterin + NADPH
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 + NADPH
L-threo-(6R,1'S,2'S)-5,6,7,8-tetrahydrobiopterin + NADP+
-
two reductive steps oxidizing NADPH
-
-
?
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 tetrahydropterin + NADPH + H+
tetrahydrobiopterin + NADP+
-
final step in the synthesis of tetrahydrobiopterin, role in detoxification of exogenous carbonyl compounds suggested
-
-
?
6-pyruvoyl-5,6,7,8-tetrahydropterin + NADPH
tetrahydrobiopterin + NADP+
-
-
-
-
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, 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
?
-
-
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
?
-
-
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 SUBSTRATES
NATURAL PRODUCTS
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
6-(S)-lactoyl-7,8-dihydropterin + NADPH
6-(L-erythro-1',2'-dihydroxypropyl)-7,8-dihydropterin + NADP+
6-pyruvoyl tetrahydropterin + NADPH
1'-oxo-2'-L-hydroxypropyl-tetrahydropterin + NADP+
-
-
-
-
?
6-pyruvoyl tetrahydropterin + NADPH
L-threo-(6R,1'S,2'S)-5,6,7,8-tetrahydrobiopterin + NADP+
6-pyruvoyl tetrahydropterin + NADPH + H+
tetrahydrobiopterin + NADP+
-
final step in the synthesis of tetrahydrobiopterin, role in detoxification of exogenous carbonyl compounds suggested
-
-
?
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+
Q64105
-
-
-
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-(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 + NADPH
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 + NADPH
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+
Q5XPX7
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+
P18297
no stereochemic specification in the publication
-
-
?
sepiapterin + NADPH + H+
7,8-dihydrobiopterin + NADP+
-
-
-
-
?
sepiapterin + NADPH + H+
tetrahydrobiopterin + NADP+
P35270
-
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
?
-
P35270
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
?
-
-
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
-
-
-
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NADPH
-
determination and analysis of the binding structure of NADPH and NADP+ to the enzyme, overview
NADPH
-
-
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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-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
Isosepiapterin
-
83% inhibition of the reductive reaction at 0.05 mM; IC50 0.0065 mM, 0.05 mM: 83% inhibition
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-acetyl-L-noradrenaline
-
weak inhibitor, N-acetyl-L-adrenaline does not bind enzyme
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
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
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
-
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
0.0501
9,10-phenanthrenequinone
-
mutant G14S, pH 6.4, 37°C; mutant R42G, pH 6.4, 37°C
0.0283
sepiapterin
-
recombinant enzyme, in 100 mM potassium phosphate buffer (pH 6.4), at 37°C
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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
0.1
Melatonin
Bombyx mori
-
recombinant enzyme, in 100 mM potassium phosphate buffer (pH 6.4), at 37°C
0.00012
Chlorpropamide
Homo sapiens
-
pH 6.4, 37°C, sepiapterin reduction; pH not specified in the publication, 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
0.00018
sulfamethoxazole
Homo sapiens
-
pH 6.4, 37°C, sepiapterin reduction; pH not specified in the publication, temperature not specified in the publication
0.000141
sulfapyridine
Homo sapiens
-
pH 6.4, 37°C, sepiapterin reduction; pH not specified in the publication, temperature not specified in the publication
0.000031
sulfasalazine
Homo sapiens
-
pH 6.4, 37°C, sepiapterin reduction; pH not specified in the publication, temperature not specified in the publication
0.000062
sulfathiazole
Homo sapiens
-
pH 6.4, 37°C, sepiapterin reduction; 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
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
10.4
-
substrate oxidation reaction, assay at; 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
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
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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
-
SPR mRNA expression is highest in all neuroblastoma clinical groups with poor outcome
additional information
-
sepiapterin reductase expression is increased in Parkinsons disease brain tissue
additional information
-
SR gene expression and activity in different developmental stages
additional information
-
SR gene expression and activity in different developmental stages
-
additional information
during the development of Musca domestica, the expression of MDSPR in the larvae is higher than other developmental stages
additional information
-
during the development of Musca domestica, the expression of MDSPR in the larvae is higher than other developmental stages
additional information
-
tissue distribution, no activity in stomach, small intestine, and muscle, overview
additional information
-
not in leukocytes and ascites tumor cells
-
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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PDB
SCOP
CATH
ORGANISM
UNIPROT
Chlorobaculum tepidum (strain ATCC 49652 / DSM 12025 / NBRC 103806 / TLS)
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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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SUBUNITS
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 * 29969, determined by cDNA sequence; x * 30000, Western blot analysis of native enzyme from crude cell extract; x * 32372, SDS-PAGE, includes His-tag residues
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
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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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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
; native enzyme from erythrocytes by hydroxylapatite and NADP+-affinity chromatography, to homogeneity
-
brain, partially, from erythrocytes to homogeneity; native enzyme partially from brain by ammonium sulfate fractionation and hydroxylapatite chromatography, and from erythrocytes to homogeneity by affinity chromatography and isoelectric focusing
-
liver; native enzyme 5000fold from liver by ammonium sulfate and protamine sulfate fractionation, and two times treatment by hydroxylapatite and anion exchange chromatography
-
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)/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
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ENGINEERING
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