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Literature summary for 1.1.1.153 extracted from

  • 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 (2013), J. Biol. Chem., 288, 19221-19237.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
expressed in Escherichia coli Homo sapiens

Protein Variants

Protein Variants Comment Organism
D257H mutant shows completely inhibited sepiapterin reduction. Mutation has only minimal effects on redox cycling Homo sapiens
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 Homo sapiens
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 Homo sapiens
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 Homo sapiens
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 Homo sapiens
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 Homo sapiens
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 Homo sapiens
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 Homo sapiens
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 Homo sapiens
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 Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
1,2-naphthoquinone
-
Homo sapiens
9,10-phenanthrenequinone
-
Homo sapiens
benzoquinone
-
Homo sapiens
dicoumarol
-
Homo sapiens
indomethacin
-
Homo sapiens
N-acetylserotonin
-
Homo sapiens
phenylquinone
-
Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0019
-
9,10-phenanthrenequinone mutant D257H, pH 6.4, 37°C Homo sapiens
0.0021
-
1,2-naphthoquinone wild-type, pH 6.4, 37°C Homo sapiens
0.0032
-
9,10-phenanthrenequinone mutant S157A, pH 6.4, 37°C Homo sapiens
0.0088
-
9,10-phenanthrenequinone wild-type, pH 6.4, 37°C Homo sapiens
0.0133
-
9,10-phenanthrenequinone mutant M205G, pH 6.4, 37°C Homo sapiens
0.0196
-
9,10-phenanthrenequinone mutant Y259A, pH 6.4, 37°C Homo sapiens
0.025
-
sepiapterin mutant Y259A, pH 6.4, 37°C Homo sapiens
0.025
-
sepiapterin wild-type, pH 6.4, 37°C Homo sapiens
0.027
-
9,10-phenanthrenequinone mutant K174L, pH 6.4, 37°C Homo sapiens
0.027
-
1,4-Naphthoquinone wild-type, pH 6.4, 37°C Homo sapiens
0.045
-
sepiapterin mutant R42G, pH 6.4, 37°C Homo sapiens
0.0501
-
9,10-phenanthrenequinone mutant G14S, pH 6.4, 37°C Homo sapiens
0.0501
-
9,10-phenanthrenequinone mutant R42G, pH 6.4, 37°C Homo sapiens
0.0503
-
sepiapterin mutant S157A, pH 6.4, 37°C Homo sapiens
0.0606
-
sepiapterin mutant D257H, pH 6.4, 37°C Homo sapiens
0.086
-
2,3-dimethoxynaphthalene-1,4-dione wild-type, pH 6.4, 37°C Homo sapiens
0.0872
-
menadione wild-type, pH 6.4, 37°C Homo sapiens
0.094
-
sepiapterin mutant N99A, pH 6.4, 37°C Homo sapiens
0.116
-
9,10-phenanthrenequinone mutant DELTA257-261, pH 6.4, 37°C Homo sapiens
0.126
-
9,10-phenanthrenequinone mutant N99A, pH 6.4, 37°C Homo sapiens
0.133
-
sepiapterin mutant M205G, pH 6.4, 37°C Homo sapiens
0.169
-
sepiapterin mutant K174L, pH 6.4, 37°C Homo sapiens
0.464
-
9,10-phenanthrenequinone mutant G18D, pH 6.4, 37°C Homo sapiens

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
28000
-
SDS-PAGE Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
lung epithelial cell
-
Homo sapiens
-

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
1.8
-
pH 6.7, 37°C Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1,2-naphthoquinone + NADPH
-
Homo sapiens ?
-
?
1,4-naphthoquinone + NADPH + H+
-
Homo sapiens ?
-
?
2,3-dimethoxynaphthalene-1,4-dione + NADPH
-
Homo sapiens ?
-
?
9,10-phenanthrenequinone + NADPH
-
Homo sapiens ?
-
?
menadione + NADPH
-
Homo sapiens ?
-
?
sepiapterin + NADPH + H+
-
Homo sapiens 7,8-dihydrobiopterin + NADP+
-
?

Synonyms

Synonyms Comment Organism
sepiapterin reductase
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.0048
-
9,10-phenanthrenequinone mutant S157A, pH 6.4, 37°C Homo sapiens
0.0053
-
sepiapterin mutant N99A, pH 6.4, 37°C Homo sapiens
0.0056
-
9,10-phenanthrenequinone mutant G14S, pH 6.4, 37°C Homo sapiens
0.0058
-
9,10-phenanthrenequinone mutant DELTA257-261, pH 6.4, 37°C Homo sapiens
0.0058
-
sepiapterin mutant S157A, pH 6.4, 37°C Homo sapiens
0.027
-
9,10-phenanthrenequinone mutant K174L, pH 6.4, 37°C Homo sapiens
0.048
-
9,10-phenanthrenequinone mutant G18D, pH 6.4, 37°C Homo sapiens
0.053
-
sepiapterin mutant R42G, pH 6.4, 37°C Homo sapiens
0.09
-
sepiapterin mutant K174L, pH 6.4, 37°C Homo sapiens
0.098
-
9,10-phenanthrenequinone mutant R42G, pH 6.4, 37°C Homo sapiens
0.107
-
9,10-phenanthrenequinone mutant D257H, pH 6.4, 37°C Homo sapiens
0.146
-
9,10-phenanthrenequinone wild-type, pH 6.4, 37°C Homo sapiens
0.156
-
sepiapterin mutant D257H, pH 6.4, 37°C Homo sapiens
0.22
-
9,10-phenanthrenequinone mutant M205G, pH 6.4, 37°C Homo sapiens
0.29
-
9,10-phenanthrenequinone mutant N99A, pH 6.4, 37°C Homo sapiens
0.428
-
sepiapterin mutant M205G, pH 6.4, 37°C Homo sapiens
0.45
-
1,4-Naphthoquinone wild-type, pH 6.4, 37°C Homo sapiens
0.6
-
sepiapterin mutant Y259A, pH 6.4, 37°C Homo sapiens
0.627
-
9,10-phenanthrenequinone wild-type, pH 6.4, 37°C Homo sapiens
0.627
-
1,2-naphthoquinone wild-type, pH 6.4, 37°C Homo sapiens
0.805
-
9,10-phenanthrenequinone mutant Y259A, pH 6.4, 37°C Homo sapiens
1.43
-
2,3-dimethoxynaphthalene-1,4-dione wild-type, pH 6.4, 37°C Homo sapiens
1.45
-
menadione wild-type, pH 6.4, 37°C Homo sapiens
1.61
-
sepiapterin wild-type, pH 6.4, 37°C Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
6.4
-
assay at Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.0005
-
phenylquinone wild-type, pH 6.7, 37°C Homo sapiens
0.0009
-
N-acetylserotonin wild-type, pH 6.7, 37°C Homo sapiens
0.0009
-
benzoquinone wild-type, pH 6.7, 37°C Homo sapiens
0.0027
-
indomethacin wild-type, pH 6.7, 37°C Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0002
-
wild-type, pH 6.7, 37°C Homo sapiens dicoumarol
0.0016
-
wild-type, pH 6.7, 37°C Homo sapiens phenylquinone
0.0026
-
wild-type, pH 6.7, 37°C Homo sapiens N-acetylserotonin
0.0028
-
wild-type, pH 6.7, 37°C Homo sapiens benzoquinone
0.0036
-
wild-type, pH 6.7, 37°C Homo sapiens 9,10-phenanthrenequinone
0.0081
-
wild-type, pH 6.7, 37°C Homo sapiens indomethacin
0.0089
-
wild-type, pH 6.7, 37°C Homo sapiens 1,2-naphthoquinone