1.1.1.153: sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)
This is an abbreviated version!
For detailed information about sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming), go to the full flat file.
Word Map on EC 1.1.1.153
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1.1.1.153
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tetrahydrobiopterin
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bh4
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aldo-keto
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cyclohydrolase
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aldose
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neurotransmitter
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pterins
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dopa-responsive
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tetrahydropterins
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6-pyruvoyl-tetrahydropterin
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n-acetylserotonin
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dystonia
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dihydropteridine
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dihydroneopterin
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6-pyruvoyl
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pteridine
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neopterin
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gtpch
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ptges
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gtp-cyclohydrolase
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5-hydroxytryptophan
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akr1b3
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6r-5,6,7,8-tetrahydrobiopterin
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epalrestat
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hyperphenylalaninaemia
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segawa
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2,4-diamino-6-hydroxypyrimidine
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medicine
- 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
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gtp-cyclohydrolase
- 5-hydroxytryptophan
- akr1b3
- 6r-5,6,7,8-tetrahydrobiopterin
- epalrestat
- hyperphenylalaninaemia
-
segawa
- 2,4-diamino-6-hydroxypyrimidine
- medicine
Reaction
Synonyms
AKR1B1, MDSPI16 protein, MDSPR, reductase, sepiapterin, sepiapterin reductase, SPR, SR
ECTree
1.1.1.153 sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)Advanced search results
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results (Engineering
Engineering on EC 1.1.1.153 - sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
F99A
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the mutant shows 3.9fold higher Km and lower Vmax (8.95%) than the wild type enzyme
W196A
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the mutant shows 8.7fold higher Km and lower Vmax (5.64%) than the wild type enzyme
D257H
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mutant shows completely inhibited sepiapterin reduction. Mutation has only minimal effects on redox cycling
DELTA257-261
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deletion of the C-terminal 5 amino acids almost completely eliminates enzyme activity. For redox cycling, the catalytic efficacy decreases to less than 1% of the wild type enzyme
G14S
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mutations in Gly14 and Gly18 in the NADPH binding motif of sepiapterin reductase results in almost complete loss of the ability to reduce sepiapterin, and a 65-75% decrease in redox cycling. For both of these mutations, the catalytic efficiencies for redox cycling decreases to 0.2% of wild type sepiapterin reductase
G18D
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mutations in Gly14 and Gly18 in the NADPH binding motif of sepiapterin reductase results in almost complete loss of the ability to reduce sepiapterin, and a 65-75% decrease in redox cycling. For both of these mutations, the catalytic efficiencies for redox cycling decreases to 0.2% of wild type sepiapterin reductase
K174L
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catalytic efficiencies (Kcat/Km) for sepiapterin reduction of S157A mutant and K174L mutant decreases to 1.8% and 0.8% of wild type sepiapterin reductase, respectively, and for redox cycling to 6.8% and 1.4%, respectively
K251X
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naturally occurring mutation in gene SPR, exon 3, causing enzyme deficiency
M205G
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mutation leads to marked reductions in the activities of both sepiapterin reduction and redox cycling. The catalytic efficiency of N99A and M205G for sepiapterin reduction decreases to approximately 1% and 5%, respectively, and for redox cycling, 5% and 25%, respectively, when compared to the wild type enzyme
N99A
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mutation leads to marked reductions in the activities of both sepiapterin reduction and redox cycling. The catalytic efficiency of N99A and M205G for sepiapterin reduction decreases to approximately 1% and 5%, respectively, and for redox cycling, 5% and 25%, respectively, when compared to the wild type enzyme
P163L
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naturally occurring mutation in gene SPR, exon 2, causing enzyme deficiency
Q119X
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naturally occurring mutation in gene SPR, exon 2, causing enzyme deficiency
R150fs
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naturally occurring mutation in gene SPR, exon 2, causing enzyme deficiency
R150G
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naturally occurring mutation in gene SPR, exon 2, causing enzyme deficiency
R42G
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mutation leads to a 90% reduction in sepiapterin reduction activity and a 50% reduction in redox cycling activity. The catalytic efficiencies for this mutant decreases to 2% and 7% of wild type sepiapterin reductase for sepiapterin reduction and redox cycling, respectively
S157A
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catalytic efficiencies (Kcat/Km) for sepiapterin reduction of S157A mutant and K174L mutant decreases to 1.8% and 0.8% of wild type sepiapterin reductase, respectively, and for redox cycling to 6.8% and 1.4%, respectively
Y259A
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mutation of Tyr259, a unique potential phosphorylation site in the C-terminal substrate transfer motif, has no major effects on sepiapterin reduction and redox cycling activity
K175I
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decreased activity against a pteridine substrate and exogenous carbonyl compound
S158D
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decreased activity against a pteridine substrate and exogenous carbonyl compound
S158D/Y171V
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double-point mutant does not show any activity towards any substrate
Y171V
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decreased activity against a pteridine substrate and exogenous carbonyl compound
additional information
additional information
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construction of insertion mutants, the gene disruption leads to complete loss of enzyme activity
additional information
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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
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construction of insertion mutants, the gene disruption leads to complete loss of enzyme activity
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additional information
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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
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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
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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
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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
