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1.14.13.39: nitric-oxide synthase (NADPH)

This is an abbreviated version!
For detailed information about nitric-oxide synthase (NADPH), go to the full flat file.

Word Map on EC 1.14.13.39

Reaction

2 L-arginine + 2 NADPH + 2 H+ + 2 O2 = 2 Nomega-hydroxy-L-arginine + 2 NADP+ + 2 H2O

Synonyms

bacterial nitric oxide synthase, bacterial nitric-oxide synthase, bNOS, bsNOS, cb-NOS, cytokine inducible NOS, DNOS, e-NOS, EC-NOS, endothelial nitric oxide synthase, endothelial nitric-oxide synthase, endothelial NO synthase, endothelial NOS, endothelium-derived relaxation factor-forming enzyme, endothelium-derived relaxing factor synthase, eNOS, i-NOS, inducible nitric oxide synthase, inducible nitric-oxide synthase, inducible NO synthase, inducible NOS, iNOS, mitochondrial NO synthase, mitochondrial-specific nitric oxide synthase, mtNOS, n-NOS, NADPH diaphorase, NADPH-d, NADPH-diaphorase, NADPHd, neuronal nitric oxide synthase, neuronal nitric-oxide synthase, neuronal NO synthase, neuronal NOS, nicotinamide adenine dinucleotide phosphate-diaphorase, nitric oxid synthase, nitric oxide synthase, nitric oxide synthase-like protein, nitric oxide synthetase, nitric-oxide synthase, nNOS, nNOSalpha, NO synthase, NO synthase type I, NO synthase type II, NO synthase type III, NO-synthase, NOS, NOS I, NOS-2, NOS1, NOS2, NOS3, synthetase, nitric oxide

ECTree

     1 Oxidoreductases
         1.14 Acting on paired donors, with incorporation or reduction of molecular oxygen
             1.14.13 With NADH or NADPH as one donor, and incorporation of one atom of oxygen into the other donor
                1.14.13.39 nitric-oxide synthase (NADPH)

Engineering

Engineering on EC 1.14.13.39 - nitric-oxide synthase (NADPH)

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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
I224V
S1179D
S617D
the phosphomimetic substitution doubles the maximum calmodulin-dependent enzyme activity and decreases the EC50(Ca2+) values for calmodulin binding and enzyme activation compared to the wild type enzyme
S617D/S1179D
the mutation doubles maximal synthase activity, partially disinhibits cytochrome c reductase activity, and lowers the EC50(Ca2+) values for calmodulin binding and enzyme activation
S617D/S635D
the maximum calmodulin-dependent synthase activity of S617/635D eNOS is about 2fold higher than the wild type activity
S635D
the substitution has little or no effect on enzyme activity
C563R
interdomain electron transfer rate is similar to that of the wildtype
D597N/M336V
mutant of nNOS, the Ki values for the nNOS double mutant increase for all inhibitors but the mutant still binds these inhibitors better than eNOS
E298D
-
comparable to wild-type in heme and flavin content, in affinity to calmodulin and dimerization
G2A
the mutant is defective in activity and cellular localization
R536E
mutant constructed to disrupt the bridging calmodulin/nitric oxide synthase interaction. The FMN-heme interdomain electron transfer rate is decreased by 96%
S562K
inducible nitric oxide synthase mutant in an oxygenase/FMN construct. The interdomain electron transfer rate constant of the mutant is decreased by one third, and its flavin fluorescence intensity per micromole per liter is diminished by approximately 24% suggesting that a positive charge at position 562 destabilizes the hydrogen-bond-mediated nitric oxide synthase/calmodulin alignment, resulting in slower FMN-heme interdomain electron transfer
C415A
-
contains no heme, no bound tetrahydrobiopterin, unable to oxidize NADPH and to synthezise nitric oxide, unaltered ability to reduce cytochrome c
C415H
-
contains nearly no heme, no bound tetrahydrobiopterin, unable to oxidize NADPH and to synthezise nitric oxide, unaltered ability to reduce cytochrome c
N695Q
site-directed mutagenesis, mutating Asn695 to Gln695 yields an iNOS that exhibits greater enzyme activity compared to wild-type. NO produced by N695Q iNOS-transformed HEK293 cells is 1.32fold greater than that of N-glycosylated iNOS, the increased enzyme activity of N695Q iNOS in HEK293 cells was caused by loss of N-glycan
V346I
slower NO-binding and dissociation than wild-type
W457A
increase in Km-value of tetrahydrobiopterin and L-arginine, decrease in NO synthesis activity, slower building of enzyme heme-NO complex and slower reactivity of heme-dioxy intermediate
N695Q
-
site-directed mutagenesis, mutating Asn695 to Gln695 yields an iNOS that exhibits greater enzyme activity compared to wild-type. NO produced by N695Q iNOS-transformed HEK293 cells is 1.32fold greater than that of N-glycosylated iNOS, the increased enzyme activity of N695Q iNOS in HEK293 cells was caused by loss of N-glycan
-
D1393E
-
normal composition, spectral properties and binding of cofactors, substrates and calmodulin, slower NADPH-dependent cytochrome c and ferricyanide reductase activity
D1393N
-
normal composition, spectral properties and binding of cofactors, substrates and calmodulin, slower NADPH-dependent cytochrome c and ferricyanide reductase activity
D1393V
-
normal composition, spectral properties and binding of cofactors, substrates and calmodulin, slower NADPH-dependent cytochrome c and ferricyanide reductase activity
DELTAG810
-
deletion changes redox behaviour of mutant. In the early stage of flavin reduction, similar to the case of wild-type, the hydroquinone FADH2-FMN quickly converts to the disemiquinone and does not accumulate. Since more FADH2-FMN is generated and not consumed quickly enough, the decreased flavin absorption band of FADH2-FMN will blur the isosbestic point after 100 ms, most likely due to a slower two-electron reduction of FMN in the mutant
V567E
little stability, no enzymic activity
V567F
enzymic activity only with N-hydroxy-L-arginine
V567L
little production of NO, lower affinity for L-arginine and N-hydroxy-L-arginine than wild-type
V567R
little stability, no enzymic activity
W678A
-
increase in Km-value of tetrahydrobiopterin, decrease in NO synthesis activity, slower building of enzyme heme-NO complex and slower reactivity of heme-dioxy intermediate
W678F
-
increase in Km-value of tetrahydrobiopterin, decrease in NO synthesis activity, slower building of enzyme heme-NO complex and slower reactivity of heme-dioxy intermediate
additional information