Information on EC 5.3.99.4 - prostaglandin-I synthase

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The expected taxonomic range for this enzyme is: Euteleostomi

EC NUMBER
COMMENTARY
5.3.99.4
-
RECOMMENDED NAME
GeneOntology No.
prostaglandin-I synthase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate = (5Z,13E)-(15S)-6,9alpha-epoxy-11alpha,15-dihydroxyprosta-5,13-dienoate
show the reaction diagram
-
-
-
-
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate = (5Z,13E)-(15S)-6,9alpha-epoxy-11alpha,15-dihydroxyprosta-5,13-dienoate
show the reaction diagram
prostaglandin endoperoxyde PGH2 prostacyclin PGI2 , a mechanism with the participation of a heme-thiolate protein is proposed
-
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate = (5Z,13E)-(15S)-6,9alpha-epoxy-11alpha,15-dihydroxyprosta-5,13-dienoate
show the reaction diagram
mechanism
-
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate = (5Z,13E)-(15S)-6,9alpha-epoxy-11alpha,15-dihydroxyprosta-5,13-dienoate
show the reaction diagram
mechanism
-
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate = (5Z,13E)-(15S)-6,9alpha-epoxy-11alpha,15-dihydroxyprosta-5,13-dienoate
show the reaction diagram
mechanism
-
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate = (5Z,13E)-(15S)-6,9alpha-epoxy-11alpha,15-dihydroxyprosta-5,13-dienoate
show the reaction diagram
radical-mediated isomerizytion with high product fidelity
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
intramolecular oxidoreduction
-
-
-
-
isomerization
-
-
-
-
isomerization
-
-
isomerization
-
-
isomerization
-
-
PATHWAY
KEGG Link
MetaCyc Link
Arachidonic acid metabolism
-
C20 prostanoid biosynthesis
-
Metabolic pathways
-
SYSTEMATIC NAME
IUBMB Comments
(5Z,13E)-(15S)-9alpha,11alpha-Epidioxy-15-hydroxyprosta-5,13-dienoate 6-isomerase
Converts prostaglandin H2 into prostaglandin I2 (prostacyclin). A heme-thiolate protein.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Aortic cytochrom P450
-
-
-
-
CYP8A1
-
-
PGI synthase
Q62969
-
PGI2 synthase
-
-
-
-
PGI2 synthase
-
-
PGI2 synthase
-
-
PGI2 synthase
-
-
PGI2 synthetase
-
-
-
-
PGI2-S
-
-
PGIS
-
-
-
-
PGIS
-
-
PGIS
Q16647
-
prostacyclin synthase
-
-
-
-
prostacyclin synthase
-
-
prostacyclin synthase
-
-
prostacyclin synthase
-
-
prostacyclin synthase
Q62969
-
prostacyclin synthase
-
-
Prostacyclin synthetase
-
-
-
-
prostacyclin/PGI2 synthase
-
-
Prostacycline synthetase
-
-
-
-
prostaglandin I synthase
Q16647
-
Prostaglandin I2 synthase
-
-
-
-
Prostaglandin I2 synthase
-
-
Prostaglandin I2 synthase
-
-
Prostaglandin I2 synthetase
-
-
-
-
Synthetase, prostacyclin
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
65802-86-0
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
recombinant enzyme
UniProt
Manually annotated by BRENDA team
recombinant protein
-
-
Manually annotated by BRENDA team
diabetic C57BL6 mice
-
-
Manually annotated by BRENDA team
transgenic mice are developed using a construct consisting of the human SP-C promotor and full-length rat prostacyclin synthase cDNA
-
-
Manually annotated by BRENDA team
cyclic, pregnant, and pseudopregnant rats
-
-
Manually annotated by BRENDA team
expression in Mus musculus
SwissProt
Manually annotated by BRENDA team
female Sprague-Dawley rat
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
physiological function
-
PGIS over-expressed mesenchymal stem cells are more resistant to free radical stress-induced apoptosis, secrete paracrine factors to enhance immunemodulation and, thus, provide cardiac protection
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-6,9alpha-epoxy-11a,15-dihydroxyprosta-5,13-dienoate
show the reaction diagram
-
i.e. prostaglandin H2
prostaglandin I2
?
10-hydroperoxyoctadeca-8,12-dienoic acid
10-oxooctadeca-8,12-dienoic acid + 10-oxodec-8-enoic acid + 10-hydroxyoctadeca-8,12-dienoic acid
show the reaction diagram
-
-
-
-
?
15-hydroperoxyeicosatetraenoic acid
13-hydroxy-14,15-epoxy-5,8,11-eicosatrienoic acid + 15-ketoeicosatetraenoic acid + 13-hydroxy-14,15-epoxy-5,8,11-eicosatrienoic acid + 15-ketoeicosatetraenoic acid
show the reaction diagram
Q16647
-
13-hydroxy-14,15-epoxy-5,8,11-eicosatrienoic acid and 15-ketoeicosatetraenoic acid result from homolytic cleavage of the O-O bond, whereas 13-hydroxy-14,15-epoxy-5,8,11-eicosatrienoic acid + 15-ketoeicosatetraenoic acid results from heterolytic cleavage. About 80% of substrate is cleaved homolytically, and maximal velocity of homolytic cleavage is about 1.4fold faster than heterolytic cleavage
-
?
15-oxo-Prostaglandin H2
15-oxo-Prostaglandin I2 + ?
show the reaction diagram
-
-
-
-
5-trans-Prostaglandin H2
?
show the reaction diagram
-
-
-
-
-
Prostaglandin G2
Prostaglandin I2 + 15-hydroperoxyprostacyclin
show the reaction diagram
-
-
-
-
-
Prostaglandin G2
Prostaglandin I2 + 15-hydroperoxyprostacyclin
show the reaction diagram
-
-
15-hydroperoxyprostacyclin decomposes to 6,15-diketo-prostaglandin F1alpha
-
prostaglandin H1
12-hydroxyheptadecadienoic acid + malondialdehyde
show the reaction diagram
-
-
-
-
prostaglandin H1
12-hydroxyheptadecadienoic acid + malondialdehyde
show the reaction diagram
-
-
-
-
-
prostaglandin H1
12-hydroxy-8,10-heptadecadienoic acid + malondialdehyde
show the reaction diagram
-
-
-
-
?
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
-
-
?
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
-
-
?
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
-
-
?
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
-
-
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
-
-
?
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
-
-
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
-
-
?
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
Q62969
-
-
-
?
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
-
-
?
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
6-keto-prostaglandin F1alpha
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2 is readily hydrolyzed to 6-keto-prostaglandin F1alpha
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
prostaglandin I2 is readily hydrolyzed to 6-keto-prostaglandin F1alpha
-
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
in vivo, this reaction is coupled to a previous one, where arachidonic acid is converted by cyclooxygenase and yields the substrate PGH2
-
-
?
Prostaglandin H2
?
show the reaction diagram
-
produces prostaglandin I2 which has opposite actions on platelet aggregatory and vasoconstrictive properties
-
-
-
Prostaglandin H2
?
show the reaction diagram
-
formation of prostaglandin I2 which is a powerful vasodilator and the most potent naturally occuring inhibitor of platlet aggregation. An imbalance in the ratio of prostaglandin I2 to thromboxane A2, a compound that has opposite biological properties may reflect some of the changes occuring in various pathological situations including thrombosis and ischemia
-
-
-
Prostaglandin H2
?
show the reaction diagram
-
formation of prostaglandin I2, which is a powerful vasodilator and the most potent natural occuring inhibitor of platelet aggregation
-
-
-
prostaglandin H2
prostacyclin
show the reaction diagram
-
-
-
-
?
prostaglandin H2
prostacyclin
show the reaction diagram
Q16647
-
-
-
?
prostaglandin H2
6-keto prostaglandin F1-alpha
show the reaction diagram
-
-
-
-
?
Prostaglandin H3
Prostaglandin I3
show the reaction diagram
-
-
-
-
-
Prostaglandin H3
Prostaglandin I3
show the reaction diagram
-
-
-
-
Prostaglandin H3
Prostaglandin I3
show the reaction diagram
-
-
-
-
-
Prostaglandin H3
Prostaglandin I3
show the reaction diagram
-
-
-
-
8-iso-Prostaglandin H2
?
show the reaction diagram
-
-
-
-
-
additional information
?
-
-
fusion protein linking cyclooxygenase COX-2 and prostacyclin synthase together, is able to convert arachidonic acid to prostaglandin G2, prostaglandin H2 and prostaglandin I2. Fusion protein may directly synthesize prostaglandin I2 from arachidonic acid with Km value of 0.0032 mM
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-6,9alpha-epoxy-11a,15-dihydroxyprosta-5,13-dienoate
show the reaction diagram
-
i.e. prostaglandin H2
prostaglandin I2
?
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
-
-
?
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
-
-
?
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
-
-
?
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
-
-
?
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
-
-
?
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
Q62969
-
-
-
?
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
-
-
-
?
Prostaglandin H2
Prostaglandin I2
show the reaction diagram
-
in vivo, this reaction is coupled to a previous one, where arachidonic acid is converted by cyclooxygenase and yields the substrate PGH2
-
-
?
Prostaglandin H2
?
show the reaction diagram
-
produces prostaglandin I2 which has opposite actions on platelet aggregatory and vasoconstrictive properties
-
-
-
Prostaglandin H2
?
show the reaction diagram
-
formation of prostaglandin I2 which is a powerful vasodilator and the most potent naturally occuring inhibitor of platlet aggregation. An imbalance in the ratio of prostaglandin I2 to thromboxane A2, a compound that has opposite biological properties may reflect some of the changes occuring in various pathological situations including thrombosis and ischemia
-
-
-
Prostaglandin H2
?
show the reaction diagram
-
formation of prostaglandin I2, which is a powerful vasodilator and the most potent natural occuring inhibitor of platelet aggregation
-
-
-
prostaglandin H2
prostacyclin
show the reaction diagram
-
-
-
-
?
prostaglandin H2
prostacyclin
show the reaction diagram
Q16647
-
-
-
?
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
cytochrome P450
-
-
-
cytochrome P450
-
cytochrome-P450 enzyme
-
cytochrome P450
-
-
-
heme
-
contains 1 heme per 49000 MW polypeptide chain
heme
-
heme-thiolate protein
heme
-
heme/protein ratio is 0.9:1
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(1R,2S)-2-phenylcyclopropanamine
-
-
13-Hydroperoxylinoleic acid
-
9,11-azoprosta-5,13-dienoic acid prevents inactivation; rapid inactivation of purified enzyme during incubation with prostaglandin H2
13-Hydroperoxylinoleic acid
-
rapid inactivation of purified enzyme during incubation with prostaglandin H2
15-hydroperoxy-5,8,11,13-eicosatetraenoic acid
-
-
15-hydroperoxy-5,8,11,13-eicosatetraenoic acid
-
-
2,4-Diamino-6-piperidinopyrimidine-3-oxide
-
-
3-Hydroperoxy-3-methyl-2-phenyl-3H-indole
-
-
6-(1-Piperidyl)-2,4-diaminopyrimidine
-
weak
9,11-Azoprosta-5,13-dienoic acid
-
-
arachidonic acid
-
-
Hydroperoxy-fatty acids
-
lipoxygenase products
-
Low density lipoprotein cholesterol
-
0.5 mg/ml stimulates 27%. Inhibition at higher concentrations. Maximal inhibition by 2 mg/ml, 64.2%
-
minoxidil
-
-
NO
-
activation at moderate concentration, reversible inhibition at high concentrations. Hemoglobin prevents both, activation and inhibition
peroxynitrite
-
-
peroxynitrite
-
substrate analog U46619 partially prevents inhibition
peroxynitrite
-
inhibits PGIS activity by nitration of tyrosine 430
peroxynitrite
-
inhibits PGIS activity by nitration of Tyr 430
Prostaglandin H1
-
slight inactivation
prostaglandin H2
-
9,11-azoprosta-5,13-dienoic acid prevents inactivation; rapid inactivation of purified enzyme during incubation with prostaglandin H2
prostaglandin H2
-
rapid inactivation of purified enzyme during incubation with prostaglandin H2
prostaglandin H2
-
9,11-azoprosta-5,13-dienoic acid prevents inactivation; inactivation originates primarily from a transition-state intermediate, not from malondialdehyde formed by hydrolysis of prostaglandin endoperoxides; rapid inactivation of purified enzyme during incubation with prostaglandin H2
rofecoxib
-
inhibitor of cyclooxygenase COX-2, additionally non-competitive inhibition of prostacyclin synthase in aortic microsomal fractions. No significant inhibition up to 0.001 mM
rofecoxib
-
inhibitor of cyclooxygenase COX-2, additionally non-competitive inhibiton of prostacyclin synthase
rofecoxib
-
-
Tetranitromethane
-
substrate analog U46619 partially prevents inhibition
trans-2-phenyl cyclopropylamine
-
-
Tranylcypromine
-
10 mM, 90% inhibition in absence or presence of 2 mM reduced glutathione
Tranylcypromine
-
-
Tranylcypromine
-
-
Tranylcypromine
-
-
U51605
-
culture of embryo in presence of U51605 decreases the implantation rate
Monoclonal antibodies
-
against prostacyclin synthase
-
additional information
-
the enzyme is deactivated by prostaglandin H2 and peroxides
-
additional information
-
proinflammatory C-reactive protein, CRP, selectively inhibits endothelium-dependent PGI2-induced dilation of coronary arterioles through peroxynitrite-mediated tyrosine nitration of prostacyclin synthase
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
13-cis-retinoic acid
-
induces prostaglandin-I synthase activity and expression of mRNA and protein, mediated by retinoic acid receptor. Actinomycin and cycloheximide both inhibit the retinoic acid-induced expression. 13-cis-Retinoic acid additionally increases the release of prostaglandin I2, both spontaneous and thrombin-induced. Co-incubation with 13-cis-retinoic acid and interleukin-1beta results in a synergic increase in the release of prostaglandin I2
dithiothreitol
-
increase in activity with increasing glutathione concentration from 0.1 mM up to 5 mM
High density lipoprotein cholesterol
-
1.0 mg/ml stimulates 21%. Lower concentrations inhibit, 16% inhibition by 0.25 mg/ml
-
interleukin-1
-
-
-
interleukin-6
-
-
NO
-
activation at moderate concentration, inhibition at high concentrations. Hemoglobin prevents both, activation and inhibition
reduced glutathione
-
increase in activity with increasing glutathione concentration from 0.1 mM up to 5 mM
TNFalpha
-
-
-
Low density lipoprotein cholesterol
-
0.5 mg/ml stimulates 27%. Inhibition at higher concentrations
-
additional information
-
the extent of prostaglandin I2 production is determined by an appropriate ratio of COX-1/COX-2 to PGIS. Human vascular endothelial cells transfected with a construct that contains COX-1 and prostaglandin-I synthase cDNAs have an equivalent increase in COX-1 and PGIS, and produce a large quantity of prostaglandin-I synthase which is more than 200fold over that produced by untransfected cells
-
additional information
-
constitutive expression of prostaglandin-I synthase and cyclooxygenase-1 in HK cells, while expression of cyclooxygenase-2 and prostaglandin-E synthase are up-regulated in response to tumor necrosis factor-alpha, tumor growth factor-beta, and lipopolysaccharide
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.059
-
15-hydroperoxyeicosatetraenoic acid
Q16647
pH 7.5, 23C, heterolytic cleavage
0.065
-
15-hydroperoxyeicosatetraenoic acid
Q16647
pH 7.5, 23C, homolytic cleavage
0.0094
-
Prostaglandin H1
-
-
0.0073
-
prostaglandin H2
-
-
0.009
-
prostaglandin H2
-
-
0.0133
-
prostaglandin H2
-
-
0.03
-
prostaglandin H2
-
at 24C
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
26.5
-
Prostaglandin H1
-
-
2.45
-
prostaglandin H2
-
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.001
-
rofecoxib
-
22C, 0.001 mM rofecoxib completely blocks cyclooxygenase COX-2
0.01
-
rofecoxib
-
22C. No significant inhibition up to 0.001 mM
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.11
-
-
production of 6-keto-prostaglandin F1alpha
0.136
-
-
-
0.975
-
-
-
1.6
-
-
solubilized microsomes
2
-
-
-
2.6
-
-
after calcium phosphate gel
4.3
-
-
after DEAE-sepharose chromatography
7.1
-
-
after hydroxyapatite chromatography
15
-
-
purified enzyme, at 24C
46
-
-
CM column, assayed at 23C using 30 microM prostaglandin H1 as the substrate
additional information
-
-
assay methods
additional information
-
-
assay of prostacyclin synthase using [5,6-3H]prostaglandin H2
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.8
7.5
-
-
7.5
-
-
kinetic assay
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
23
-
-
kinetic assay
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
normal aortic endothelium. Prostaglandin cyclase, cyclooxygenase COX-1 and thromboxane synthase are widely distributed throughout the endothelium. There is greater co-distribution of prostacyclin synthase with isoform COX-1 compared to isoform COX-2
Manually annotated by BRENDA team
-
normal aortic endothelium. Co-distribution of prostaglandin cyclase and cyclooxygenase COX-1, while expression of cyclooxygenase COX-2 is not detected in endothelium
Manually annotated by BRENDA team
-
normal aortic endothelium. Co-distribution of prostaglandin cyclase and cyclooxygenase COX-1, with only minor expression of cyclooxygenase COX-2 in endothelium
Manually annotated by BRENDA team
-
significant suppression of enzyme activity in parallel with increased superoxide and enzyme nitration in the aortas of diabetic C57BL6 mice, but less effect in diabetic mice either lacking endothelial nitric oxide synthase or overexpressing human superoxide dismutase
Manually annotated by BRENDA team
-
atherosclerotic aorta
Manually annotated by BRENDA team
-
smooth muscle
Manually annotated by BRENDA team
-
coronary arteriole
Manually annotated by BRENDA team
-
vascular
Manually annotated by BRENDA team
-
exposure of isolated coronary arteries to high glucose switches angiotensin II-stimulated prostacyclin-dependent relaxation into a persitent vascoconstriction. High glucose, but not mannitol, significantly increases superoxide and nitration of tyrosine in prostacyclin synthase. Concurrent administration of polyethylene-coated superoxide dismutase, L-nitroarginine methyl ester, or sepiapterin abolishes enzyme nitration, as well as its association with endothelial nitric oxide synthase
Manually annotated by BRENDA team
-
ischemic cortex, ipsilateral penumbra area, pyriform cortex, hippocampus, leptomeninges
Manually annotated by BRENDA team
-
study on involvement of enzyme polymorphism in adenomatous or hyperplastic colorectal polyps. The enzyme promoter polymorphism may affect risk of colorectal polyps and modify the effects of nonsteroidal anti-inflammatory drug use on polyp risk
Manually annotated by BRENDA team
-
widely distributed among different cell types, specific binding sites which may mediate luteotropic actions of the enzyme are only present in small and large luteal cells
Manually annotated by BRENDA team
-
normal aortic endothelium. Prostaglandin cyclase, cyclooxygenase COX-1 and thromboxane synthase are widely distributed throughout the endothelium. There is greater co-distribution of prostacyclin synthase with isoform COX-1 compared to isoform COX-2
Manually annotated by BRENDA team
-
normal aortic endothelium. Co-distribution of prostaglandin cyclase and cyclooxygenase COX-1, while expression of cyclooxygenase COX-2 is not detected in endothelium
Manually annotated by BRENDA team
-
normal aortic endothelium. Co-distribution of prostaglandin cyclase and cyclooxygenase COX-1, with only minor expression of cyclooxygenase COX-2 in endothelium
Manually annotated by BRENDA team
-
constitutive expression of prostaglandin-I synthase and cyclooxygenase-1 in HK cells, while expression of cyclooxygenase-2 and prostaglandin-E synthase are up-regulated in response to tumor necrosis factor-alpha, tumor growth factor-beta, and lipopolysaccharide
Manually annotated by BRENDA team
-
extensive co-localization of prostacyclin synthase and cyclooxygenase COX-2
Manually annotated by BRENDA team
-
tendon, fascia and arteries leading to the muscle
Manually annotated by BRENDA team
-
vascular and nonvascular
Manually annotated by BRENDA team
-
of cyclic, pregnant, and pseudopregnant rats. Expression of prostacyclin synthase is increases during early pregnancy and decreases gradually from day 5.5 to 6.5. Later during pregnancy, expression of enzyme is maximal on day 12 and decrease to the end of pregnancy. During pseudopregnancy, both prostaglandin D synthase and prostacyclin synthase are increased in a time-dependent manner and are maximal at day 5. Both enzymes are found in luminal as well as glandular epithelial cells and in stroma during late pregnancy
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
one transmembrane segment in the NH2-terminal domain of the enzyme
Manually annotated by BRENDA team
-
membrane-bound
Manually annotated by BRENDA team
-
anchors to the membrane with a single N-terminal transmembrane domain, the bulk of the enzyme is located at the cytosolic side of ER
Manually annotated by BRENDA team
-
the recombinant enzyme associates with host cell membranes
Manually annotated by BRENDA team
-
localization of recombinant enzyme in infected Sf21 cells
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
48000
-
-
mutant C441H, SDS-PAGE; wild-type, SDS-PAGE
52000
-
-
-
52000
-
Q62969
determined by SDS-PAGE and Western Blot analysis
52000
-
-
-
52000
-
-
determined by SDS-PAGE and Western Blot analysis
56000
-
-
monomer, SDS-PAGE, Western Blot
56500
-
Q62969
determined by SDS-PAGE and Western Blot analysis
57000
-
-
chimer PGIS/TXAS(8-27), monomer, SDS-PAGE; mutant delta-20-PGIS, monomer, SDS-PAGE; wild-type, monomer, SDS-PAGE
57000
-
-
determined by SDS-PAGE and Western Blot analysis
57100
-
-
calculated from the primary structure, deduced from the cDNA sequence
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 52000, SDS-PAGE; x * 56628, calculation from nucleotide sequence
?
-
x * 49200, SDS-PAGE
?
-
x * 52000, SDS-PAGE
?
-
x * 56675, calculation from nucleotide sequence
?
-
x * 57000, deduced from nucleotide sequence
monomer
-
-
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
diabetes induces prostacyclin synthase nitration in carotid plaques
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant protein without ligand, in complex with inhibitor minoxidil, or with substrate analogue U51605. Upon stereo-specific binding of substrate, conformational changes take place at the proximal side and in the heme itself. Mechanism is a radical-mediated isomerization with high product fidelity
-
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
100
-
-
5-7 min, destroys activity in crude enzyme extract
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
6 M guanidine-HCl inactivates enzyme in crude extract
-
ORGANIC SOLVENT
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Triton X-100
-
within 30 s, about 75% of PGH2 is presented to the PGIS active side and isomerized to PGI2 by the membrane-bound PGIS. In contrast, only about 20% of the substrate is isomerized to the product by the detergent-solubilized (Triton X-100) PGIS. Replacement of the membrane with detergent does not alter the PGIS active side conformation, but affects the substrate presentation
OXIDATION STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
the prostacyclin synthase is unusually sensitive to the redox state or sulfhydryl oxidation of the enzyme
-
3127
human PGIS is significantly unstable when the heme cofactor appears in the reduction and/or reduction-CO binding state
-
662059
destructive action of a nascent oxidizing agent released from prostaglandin G1, 15-hydroperoxy-prostaglandin E1, 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid, and 12-hydroxy-5,8,10,14-eicosatetraenoic acid is prevented by 2-aminomethyl-4-tert-6-iodophenol
-
37459
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-80C, partially purified enzyme, stable for 2-3 months
-
-90C, gradual loss of activity of enzyme in crude extract
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant enzyme
-
recombinant enzyme is purified to homogeneity
-
to electrophoretic homogeneity
-
partial
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Escherichia coli
-
expressed in Mus musculus mesenchymal stem cells
-
expression in Cos-1 cells
-
expression in COS-7 cells
-
expression in Escherichia coli
-
expression in Spodoptera frugiperda 21 cells
-
expression with C-terminal His-tag and hydrophilic aminoterminal segment MAKKTSS
Q16647
for expression in Escherichia coli cells
-
from endothelilal cells
-
fusion protein linking cyclooxygenase COX-2 and prostacyclin synthase together, separated by a transmembrane domain of 10 or 22 residues
-
into the pcDNA3.1 vector for transfection of insulin-producing RINm5F cells
-
expression in alveolar and airway epithelial cells from Mus musculus
-
expression in HEK 293 cells
-
GFP-tagged cDNA containing the full-length rat prostacyclin synthase gene is inserted into an adenoviral DNA construct for in vitro gene transfer to murine and human mesenchymal stem cells
Q62969
specific transgenic expression in mouse kidney using rat KSP-cadherin promoter
Q62969
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
hyperglycemia and palmitate increase prostacyclin synthase nitration and reduce its activity
-
a dramatic loss in PGIS mRNA levels is observed in primary lung tumor samples
-
PGIS mRNA and protein expression is increased in response to mechanical cyclical stretch in both spinal ligament and uterine myometrial cells, up-regulation is observed in umbilical vein endothelial cell treated with a thromboxane analogue
-
after 16 weeks the prostacyclin synthase mRNA levels are reduced
-
after 8 weeks on fat diet, aortic arches from low-density lipoprotein receptor deficient, LDL r-KO, mice shows a significant increase in prostacyclin synthase levels
-
for overexpression of prostacyclin synthase transgenic mice, carrying the rat prostacyclin synthase gene, are developed
-
interleukin-1beta (10 ng/ml, 24 h incubation) does not alter PGIS protein expression
-
angiotensin II (0.1 mM, 24 h incubation) induces PGIS mRNA expression. Pretreatment with losartan (0.01 mM), PD98059 (0.025 mM) or SB203580 (0.01 mM) prevents PGIS protein expression induced by the combination of angiotensin II and interleukin-1beta
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
C441H
-
no heme-binding ability, no activity
DELTA-20-PGIS
-
PGH2 presentation to the membrane-bound mutant has a 2 to 3fold delay compared to that of membrane-bound wild-type PGIS
additional information
-
fusion protein linking cyclooxygenase COX-2 and prostacyclin synthase together, separated by a transmembrane domain of 10 or 22 residues. Expressed protein is able to convert arachidonic acid to prostaglandin G2, prostaglandin H2 and prostaglandin I2. Fusion protein may directly synthesize prostaglandin I2 from arachidonic acid with Km value of 0.0032 mM
PGIS/TXAS(8-27)
-
the first 20 membrane anchor residues of human PGIS are replaced by the corresponding membrane anchor region of human TXAS (thromboxane A2 synthase). Efficiency of the isomerization of PGH2 to PGI2 is slowed down with approximately 25, 65, and 85% at 30, 60, and 120 s reactions, compared to the wild-type PGIS, respectively
additional information
Q62969
specific transgenic expression of prostacyclin synthase in mouse kidney results in increased in urinary 6-keto-prostaglandin F1alpha. Transgenic mice demonstrate endotoxemia-related acute kidney injury with low doses of lipopolysaccharide, which do not alter wild-type glomerular filtration rate. They also show increase in renal cAMP content
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
formation of monoclonal antibodies against prostacyclin synthase
medicine
-
exposure of isolated coronary arteries to high glucose switches angiotensin II-stimulated prostacyclin-dependent relaxation into a persitent vascoconstriction. High glucose, but not mannitol, significantly increases superoxide and nitration of tyrosine in prostacyclin synthase. Concurrent administration of polyethylene-coated superoxide dismutase, L-nitroarginine methyl ester, or sepiapterin abolishes enzyme nitration, as well as its association with endothelial nitric oxide synthase
medicine
-
overexpression of PGIS is highly effective in controlling vascular diseases and ischemia-reperfusion tissue injury, gene transfer of bicistronic COX-1/PGIS has the potential for treatment of diverse clinical disorders including vascular diseases, pulmonary hypertension, and ischemia-reperfusion cerebral and cardiac injury
medicine
-
the enzyme acts as a regulator of thyroid papillary carcinoma proliferation, increased expression levels may play a role in the pathogenesis of these tumors
medicine
-
upregulation of prostaglandin I2 synthesis by expression of a fusion protein linking cyclooxygenase COX-2 and prostacyclin synthase shows strong activity in inhibiting platelet aggregation induced by arachidonic acid in vitro and may be used for therapeutic inventions for strokes and heart attacks
medicine
-
study on involvement of enzyme polymorphism in adenomatous or hyperplastic colorectal polyps. The enzyme promoter polymorphism may affect risk of colorectal polyps and modify the effects of nonsteroidal anti-inflammatory drug use on polyp risk
medicine
-
tyrosine nitration of prostacyclin synthase is correlated with an excessive inflammatory response in atherosclerotic carotid arteries from patients with type 2 diabetes
medicine
-
prostacyclin synthase may be chemopreventive in cancer
medicine
-
prostacyclin synthase overexpression apparently protects insulin-producing cells against cytokine toxicity via suppression of endoplasmic reticulum and mitochondrial stress-mediated cell death pathways
medicine
-
significant suppression of enzyme activity in parallel with increased superoxide and enzyme nitration in the aortas of diabetic C57BL6 mice, but less effect in diabetic mice either lacking endothelial nitric oxide synthase or overexpressing human superoxide dismutase
medicine
-
after culture of embryos in presence of the selective cyclooxygenase-1 inhibitor SC560, the selective cyclooxygenase-2 inhibitor NS398, or the selective prostacyclin synthase inhibitor U51605 in a 48-h culture, the implantation rate decreases with exposure to either the cyclooxygenase-2 inhibitor of the prostaglandin-I synthase inhibitor, which is increased further after supplementation with prostaglandin I2. The level of prostaglandin I2 is also higher at the 8-16 cell stage, compaction and blastocyst stage than prostaglandin E2
medicine
-
it is hypothesized that the combination of prostacyclin synthase overexpression and epidermal growth factor receptor tyrosine kinase inhibitor, EGFR TKI, would lead to augmented chemoprevention for lung cancer
medicine
-
manipulation of prostaglandin production distal to cyclooxygenase significantly reduces lung carcinogenesis in a tobacco smoke exposure model
medicine
-
prostaglandin-I synthase protects the brain by enhancing prostaglandin I2 synthesis and creating a favorable prostaglandin I2/thromboxane A2 ratio, prostaglandin-I synthase expression after ischemic insult is important in promoting neuronal cell survival
medicine
Q62969
synthesis of prostaglandin by enzyme contributes to renal protection against endotoxemia-related acute kidney injury
medicine
Q62969
sustained release of prostaglandin I2 enhances the proangiogenic function of mesenchymal stem cells and subsequent muscle cell regrowth in the ischemic tissue suggesting potential therapeutic benefits of cell-based gene therapy for critical limb ischemia
medicine
-
by impairing prostacyclin synthase function, and thus PGI2 release, C-reactive protein, CRP, could promote endothelial dysfunction and participate in the development of coronary artery disease