Information on EC 1.14.99.1 - prostaglandin-endoperoxide synthase

Word Map on EC 1.14.99.1
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)
Please login to have access to the AMENDA and FRENDA data

The enzyme appears in viruses and cellular organisms

top print hide
EC NUMBER
COMMENTARY hide
1.14.99.1
-
top print hide
RECOMMENDED NAME
GeneOntology No.
prostaglandin-endoperoxide synthase
top print hide
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
arachidonate + AH2 + 2 O2 = prostaglandin H2 + A + H2O
show the reaction diagram
top print hide
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
redox reaction
-
-
-
-
reduction
top print hide
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Arachidonic acid metabolism
-
-
C20 prostanoid biosynthesis
-
-
Metabolic pathways
-
-
arachidonic acid metabolism
-
-
top print hide
SYSTEMATIC NAME
IUBMB Comments
(5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate,hydrogen-donor:oxygen oxidoreductase
This enzyme acts both as a dioxygenase and as a peroxidase.
top
top print hide
CAS REGISTRY NUMBER
COMMENTARY hide
39391-18-9
-
9055-65-6
-
top print hide
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
collected on the coast of the Baltic Sea in Kassari Bay
UniProt
Manually annotated by BRENDA team
collected from the coast of Kanagawa Prefecture in Tokyo Bay
UniProt
Manually annotated by BRENDA team
squirrel monkey
-
-
Manually annotated by BRENDA team
top print hide
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
the algal PGHS lacks structural elements identified in all known animal PGHSs, such as epidermal growth factor-like domain and helix B in the membrane binding domain. The key residues of animal PGHS, like catalytic Tyr385 and heme liganding His388 are conserved in the algal enzyme, but the amino acid residues shown to be important for substrate binding and coordination, and the target residues for nonsteroidal anti-inflammatory drugs, Arg120, Tyr355, and Ser530, are not found at the appropriate positions in the algal sequences. The preferred substrate for the algal PGHS is arachidonic acid with cyclooxygenase reaction rate remarkably higher than values reported for mammalian PGHS isoforms
malfunction
PGHS-1 inhibition in activated human plateletts significantly decreases PGHS-1-dependent thromboxane B2 formation in parallel with a decrease in platelet aggregation
metabolism
physiological function
additional information
top print hide
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoic acid + AH2 + O2
? + A + H2O
show the reaction diagram
(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoic acid + AH2 + O2
? + A + H2O
show the reaction diagram
substrate binding structure and nonproductive conformation, overview
-
-
?
8,11,14-eicosatrienoic acid + O2
prostaglandin G1 + ?
show the reaction diagram
8,11,14-eicosatrienoic acid + O2
prostaglandin H1 + ?
show the reaction diagram
arachidonate + 2 O2
prostaglandin G2
show the reaction diagram
-
-
-
-
?
arachidonate + AH2 + 2 O2
prostaglandin G2 + A + H2O
show the reaction diagram
arachidonate + AH2 + 2 O2
prostaglandin H2 + A + H2O
show the reaction diagram
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
arachidonate + electron donor + O2
prostaglandin H2 + oxidized electron donor + H2O
show the reaction diagram
arachidonate + reduced N,N,N',N'-tetramethylphenylenediamine + 2 O2
prostaglandin G2 + oxidized N,N,N',N'-tetramethylphenylenediamine + H2O
show the reaction diagram
-
-
-
?
arachidonate + reduced N,N,N',N'-tetramethylphenylenediamine + 2 O2
prostaglandin H2 + oxidized N,N,N',N'-tetramethylphenylenediamine + H2O
show the reaction diagram
arachidonic acid + 2 O2
prostaglandin G2
show the reaction diagram
cyclooxygenase reaction, arachidonic acid as electron donor
-
-
?
arachidonic acid + 3,4-methylenedioxyamphetamine
?
show the reaction diagram
-
postulated bioactivation to a neurodegenerative free radical intermediate that can initiate the formation of reactive oxygen species
-
-
?
arachidonic acid + 3,4-methylenedioxymethamphetamine
?
show the reaction diagram
-
postulated bioactivation to a neurodegenerative free radical intermediate that can initiate the formation of reactive oxygen species
-
-
?
arachidonic acid + AH2 + 2 O2
15(R)-hydroxy-eicosatetraenoic acid + A + ?
show the reaction diagram
arachidonic acid + AH2 + 2 O2
15-hydroperoxy-9alpha,11alpha-peroxiprosta-5,13-dienoic acid + A + ?
show the reaction diagram
-
-
-
?
arachidonic acid + AH2 + 2 O2
6-keto-prostaglandin F1alpha + A + ?
show the reaction diagram
-
activity assay
-
-
?
arachidonic acid + AH2 + 2 O2
prostaglandin E2 + A + ?
show the reaction diagram
-
-
-
?
arachidonic acid + AH2 + O2
prostaglandin E2 + ?
show the reaction diagram
arachidonic acid + methamphetamine
?
show the reaction diagram
-
postulated bioactivation to a neurodegenerative free radical intermediate that can initiate the formation of reactive oxygen species
-
-
?
cis-11,14-eicosadienoic acid + AH2 + O2
?
show the reaction diagram
-
-
-
?
cis-4,7,10,13,16,19-docosahexaenoic acid + AH2 + O2
?
show the reaction diagram
-
-
-
?
cis-5,8,11,14,17-eicosapentaenoic acid + AH2 + O2
?
show the reaction diagram
-
-
-
?
cis-5,8,11,14-eicosatetraenoic acid + AH2 + O2
?
show the reaction diagram
-
-
-
?
cis-7,10,13,16-docosatetraenoic acid + AH2 + O2
?
show the reaction diagram
-
-
-
?
cis-8,11,14-eicosatrienoic acid + AH2 + O2
?
show the reaction diagram
-
-
-
?
gamma-linolenic acid + AH2 + O2
?
show the reaction diagram
-
-
-
?
guaiacol + trans-5-phenyl-4-pentenyl-1-hydroperoxide
?
show the reaction diagram
-
-
-
-
?
H2O2 + guaiacol
?
show the reaction diagram
-
peroxidase activity
-
-
?
H2O2 + N,N,N',N'-tetramethyl-p-phenylenediamine
?
show the reaction diagram
-
peroxidase activity
-
-
?
linoleic acid + AH2 + O2
9-hydroxyoctadecadienoic acid + 13-hydroxyoctadecadienoic acid + ?
show the reaction diagram
linolenic acid + AH2 + O2
?
show the reaction diagram
-
-
-
?
prostaglandin G2 + AH2
prostaglandin H2 + A + H2O
show the reaction diagram
-
-
-
-
?
additional information
?
-
top print hide
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
arachidonate + 2 O2
prostaglandin G2
show the reaction diagram
-
-
-
-
?
arachidonate + AH2 + 2 O2
prostaglandin G2 + A + H2O
show the reaction diagram
arachidonate + AH2 + 2 O2
prostaglandin H2 + A + H2O
show the reaction diagram
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
prostaglandin G2 + AH2
prostaglandin H2 + A + H2O
show the reaction diagram
-
-
-
-
?
additional information
?
-
top print hide
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Hematin
-
;
iron-protoporphyrin IX
each subunit contains a molecule of Fe3+-protoporphyrin IX noncovalently attached to the enzyme, the heme group is essential for both enzyme activities; each subunit contains a molecule of Fe3+-protoporphyrin IX noncovalently attached to the enzyme, the heme group is essential for both enzyme activities
additional information
-
top print hide
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Fe2+
ferric heme enzyme
Mn3+
-
substitution of ferric heme by MnIII protoporphyrin IX greatly diminishes the peroxidase activity, but has little effect on the cyclooxygenase activity
top print hide
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,10-phenanthroline
-
weak
1-Mercapto-9,11,15-trihydroxyprosta-5,13-diene
-
inhibition of prostaglandin G1 synthesis
1-Mercapto-9-oxo-11,15-dihydroxyprosta-5,13-dione
-
inhibition of prostaglandin G1 synthesis
12-nitroarachidonic acid
nitro-fatty acid inhibition is due to a slow, tightly binding mechanism, it inhibits oxygenase and peroxidase activity PGHS-1, kinetics, overview. Inactivation of PGHS by nitroarachidonic acid involves two sequential steps: an initial reversible binding event, followed by a practically irreversible event leading to an inactivated enzyme. Inactivation is associated with irreversible disruption of heme binding to the protein, the inhibitor induces heme release from Fe2+-protoporphyrin-PGHS-1. In activated human platelets, nitroarachidonic acid significantly decreases PGHS-1-dependent thromboxane B2 formation in parallel with a decrease in platelet aggregation
14-nitroarachidonic acid
nitro-fatty acid inhibition is due to a slow, tightly binding mechanism, it inhibits oxygenase and peroxidase activity PGHS-1, kinetics, overview. Inactivation of PGHS by nitroarachidonic acid involves two sequential steps: an initial reversible binding event, followed by a practically irreversible event leading to an inactivated enzyme. Inactivation is associated with irreversible disruption of heme binding to the protein, the inhibitor induces heme release from Fe2+-protoporphyrin-PGHS-1. In activated human platelets, nitroarachidonic acid significantly decreases PGHS-1-dependent thromboxane B2 formation in parallel with a decrease in platelet aggregation
15-nitroarachidonic acid
nitro-fatty acid inhibition is due to a slow, tightly binding mechanism, it inhibits oxygenase and peroxidase activity PGHS-1, kinetics, overview. Inactivation of PGHS by nitroarachidonic acid involves two sequential steps: an initial reversible binding event, followed by a practically irreversible event leading to an inactivated enzyme. Inactivation is associated with irreversible disruption of heme binding to the protein, the inhibitor induces heme release from Fe2+-protoporphyrin-PGHS-1. In activated human platelets, nitroarachidonic acid significantly decreases PGHS-1-dependent thromboxane B2 formation in parallel with a decrease in platelet aggregation
2,2'-bipyridyl
-
weak
2,3-Dimercaptopropanol
-
inhibition of prostaglandin G1 synthesis
2-hydroxybutyric acid
-
weak
5,8,11,14-Eicosatetraynoic acid
5-bromo-2-[4-fluorophenyl]-3-[4-methylsulfonylphenyl]-thiophene
6-methoxy-2-naphthyl acetic acid
-
active metabolite of nabumetone, isozyme 1, 50% inhibition at 0.2-0.8 mM, isozyme 2, 50% inhibition at 0.015-0.55 mM
6-methylnaphthylacetic acid
-
recombinant protein, 50% inhibition at 0.08-0.1 mM
6-[2,4-difluorophenoxy]-5-methyl-sulfonylamino-1-indanone
-
CGP28238, an isozyme-2 specific inhibitor, 65% inhibition at 100 nM
8-hydroxyquinoline
-
-
9,11-Dihydroxy-15S-mercaptoprosta-5,13-dienoic acid
-
or 15R-isomer, inhibition of prostaglandin G1 synthesis
9-nitroarachidonic acid
nitro-fatty acid inhibition is due to a slow, tightly binding mechanism, it inhibits oxygenase activity and peroxidase activity of PGHS-1, kinetics, overview. Inactivation of PGHS by nitroarachidonic acid involves two sequential steps: an initial reversible binding event, followed by a practically irreversible event leading to an inactivated enzyme. Inactivation is associated with irreversible disruption of heme binding to the protein, the inhibitor induces heme release from Fe2+-protoporphyrin-PGHS-1. In activated human platelets, nitroarachidonic acid significantly decreases PGHS-1-dependent thromboxane B2 formation in parallel with a decrease in platelet aggregation
acetoacetic acid
-
weak
Acetylsalicylic acid
albumin
-
alpha-linolenic acid
-
;
anilorac
-
isozyme 1, 50% inhibition at 0.0007 mM, isozyme 2, 50% inhibition at 0.009 mM
-
aspirin
bicarbonate
-
bicarbonate enhances peroxynitrite-mediated peroxidase inactivation
Butyric acid
-
-
BW 755C
-
recombinant protein, 50% inhibition at 0.01-0.02 mM
celecoxib
-
;
crotonic acid
-
-
DCM-extract of Angelicae dahuricae radix
-
0.1% inhibition of PGHS-1; 38.8% inhibition of PGHS-2
-
DCM-extract of Angelicae sinsesis radix
-
55.8% inhibition of PGHS-2; 75.0% inhibition of PGHS-1
-
DCM-extract of Atractylodis lanceae rhizoma
-
46.9% inhibition of PGHS-1; 50.3% inhibition of PGHS-2
-
DCM-extract of Atractylodis macrocephalae rhizoma
-
47.0% inhibition of PGHS-2; 58.6% inhibition of PGHS-1
-
DCM-extract of Cinnamomi ramulus
-
48.4% inhibition of PGHS-2; 73.5% inhibition of PGHS-1
-
DCM-extract of Houttuyniae herba
-
40.9% inhibition of PGHS-2; 46.8% inhibition of PGHS-1
-
DCM-extract of Notopterygii rhizoma seu radix
-
-2.1% inhibition of PGHS-2; 42.6% inhibition of PGHS-1
-
DCM-extract of Piperis sarmentosi herba
-
10.1% inhibition of PGHS-2; 47.2% inhibition of PGHS-1
-
DCM-extract of Platycodi radix
-
70.1% inhibition of PGHS-2; 77.8% inhibition of PGHS-1
-
DCM-extract of Zanthoxyli pericarpium
-
18.3% inhibition of PGHS-1; 31.3% inhibition of PGHS-2
-
DCM-extract of Zingiberis rhizoma
-
41.3% inhibition of PGHS-2; 52.9% inhibition of PGHS-1
-
diclofenac
diethyldithiocarbamate
-
-
Dihydrolipoic acid
-
inhibition of prostaglandin G1 synthesis
dithiothreitol
-
inhibition of prostaglandin G1 synthesis
DL-Propanolol
-
-
docosahexaenoic acid
-
isozyme 1, 50% inhibition at 0.011 mM, isozyme 2, 50% inhibition at 0.015 mM
DUP-697
Eicosa-5,8,11,14-tetraynoic acid
-
-
ellagic acid
-
at high concentration and in presence of cofactors inhibition, at low concentrations stimulation
etodalac
-
recombinant protein, 50% inhibition at 0.06-0.07 mM
ETYA
-
recombinant protein, 50% inhibition at 0.015-0.025 mM
fatty acid
-
of low molecular mass
fenclofenac
-
isozyme 1, 50% inhibition at 0.007 mM, isozyme 2, 50% inhibition at 0.004 mM
flosulide
-
selective for isozyme 2, 50% inhibition at 130 nM
Flufenamic acid
-
50% inhibition at 0.02 mM
flurbiprofen
Haptoglobin
-
-
-
Human serum
-
-
-
Ibuprofen
indomethacin
Ketoprofen
L-745
-
isozyme 1, 50% inhibition at 0.369 mM, isozyme 2, 50% inhibition at 0.002 mM
-
linoleic acid
-
;
Meclofenamic acid
Mefenamic acid
-
isozyme 1, 50% inhibition at 0.01 mM, isozyme 2, 50% inhibition at 0.0003 mM
meloxicam
-
isozyme 1, 50% inhibition at 0.005 mM, isozyme 2, 50% inhibition at 0.0004 mM
n-hexane extract of Angelicae dahuricae radix
-
42.4% inhibition of PGHS-2; 52.5% inhibition of PGHS-1
-
n-hexane extract of Angelicae sinsesis radix
-
61.5% inhibition of PGHS-2; 73.0% inhibition of PGHS-1
-
n-hexane extract of Atractylodis lanceae rhizoma
-
67.4% inhibition of PGHS-1; 68.3% inhibition of PGHS-2
-
n-hexane extract of Atractylodis macrocephalae rhizoma
-
46.1% inhibition of PGHS-1; 48.9% inhibition of PGHS-2
-
n-hexane extract of Cinnamomi ramulus
-
23.6% inhibition of PGHS-2; 46.6% inhibition of PGHS-1
-
n-hexane extract of Houttuyniae herba
-
43.4% inhibition of PGHS-2; 50.3% inhibition of PGHS-1
-
n-hexane extract of Notopterygii rhizoma seu radix
-
64.9% inhibition of PGHS-2; 69.6% inhibition of PGHS-1
-
n-hexane extract of Piperis sarmentosi herba
-
52.4% inhibition of PGHS-1; 65.0% inhibition of PGHS-2
-
n-hexane extract of Platycodi radix
-
48.7% inhibition of PGHS-1; 55.1% inhibition of PGHS-2
-
n-hexane extract of Zanthoxyli pericarpium
-
24.9% inhibition of PGHS-2; 48.5% inhibition of PGHS-1
-
n-hexane extract of Zingiberis rhizoma
-
77.5% inhibition of PGHS-2; 83.4% inhibition of PGHS-1
-
N-[2-cyclohexyloxy-4-nitrophenyl]methanesulfonamide
naproxen
niflumic acid
-
isozyme 1, 50% inhibition at 0.016 mM, isozyme 2, 50% inhibition at 0.0001 mM
nimesulide
Non-steroidal anti-inflammatory agents
-
NS-398
O2
-
the cyclooxygenase reaction is inhibited by an excess of dissolved oxygen, 0.5 mM O2 causes twofold decrease in the initial rate and maximal yield
oleic acid
-
;
p-Aminophenol
-
-
PD-98059
-
MEK inhibitor, blocks specifically the activation of ERK1/2 and the PGHS-2 mRNA response to oxygen and glucose depivation, hence ERK is a mediator of PGHS-2 gene expression
peroxynitrite
-
-
piroxicam
propionic acid
-
-
quercetin
quercetin 3-O-glucoside
SB203580
-
inhibitor of p38, reduces the PGHS-2 response to oxygen and glucose depivation by approximately 50%
SC-560
SC58125
-
isozyme 1, 50% inhibition at 0.039 mM, isozyme 2, 50% inhibition at 0.0003 mM
sulindac sulfide
-
isozyme 1, 50% inhibition at 0.0004 mM, isozyme 2, 50% inhibition at 0.012 mM
suprofen
-
isozyme 1, 50% inhibition at 0.0005 mM, isozyme 2, 50% inhibition at 0.002mM
Tannic acid
-
at high concentration and in presence of cofactors inhibition, at low concentrations stimulation
U0126
-
MEK inhibitor, blocks specifically the activation of ERK1/2 and the PGHS-2 mRNA response to oxygen and glucose depivation, hence ERK is a mediator of PGHS-2 gene expression
valeryl salicylate
-
-
additional information
-
top print hide
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5-hydroxytryptamine
-
stimulates
arachidonate
-
-
arachidonic acid
-
exogenous, increases hPHS activity
benzoquinone
-
stimulates conversion of prostaglandin G1 to H1
cysteine
-
stimulates
dopamine
ellagic acid
-
at high concentration and in presence of cofactors inhibition, at low concentrations stimulation
epinephrine
glutathione
-
promotes prostaglandin H synthase-dependent formation of oxidative stress biomarkers malondialdehyde and 15(S)-8-iso-prostaglandin F2alpha; promotes prostaglandin H synthase-dependent formation of oxidative stress biomarkers malondialdehyde and 15(S)-8-iso-prostaglandin F2alpha
Hemin
-
activates
hydroperoxyeicosatetraenoic acid
-
-
-
hydroquinone
indole
-
stimulates conversion of prostaglandin G1 to H1
kynurenine
-
stimulates conversion of prostaglandin G1 to H1
Melatonin
norepinephrine
-
-
Oestrogens
-
weak stimulation
-
peroxynitrite
-
peroxidase activity, MS-analysis reveals that tyrosine 385 is a target for nitration by ONOO- only when heme is present
phenylalanine
-
stimulates conversion of prostaglandin G1 to H1
quinol
-
stimulates
reduced glutathione
-
stimulates
serotonin
Tannic acid
-
at high concentration and in presence of cofactors inhibition, at low concentrations stimulation
Thyroid hormones
-
weak stimulation
-
thyrotropin
-
tissue-specific stimulation in thyroid
-
tryptophan
-
stimulates conversion of prostaglandin G1 to H1
tyrosine
-
stimulates conversion of prostaglandin G1 to H1
additional information
-
top print hide
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0368
(4Z,7Z,10Z,13Z,16Z,19Z)-Docosahexaenoic acid
pH 8.0, 25°C, COX-2 mutant N580A
0.00945
(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoic acid
pH 8.0, 25°C, COX-2 mutant N580A
0.0031 - 0.082
alpha-linolenic acid
0.0009 - 0.015
arachidonate
0.001 - 0.16
arachidonic acid
0.0052 - 0.0091
cis-11,14-eicosadienoic acid
0.0011 - 0.07
cis-4,7,10,13,16,19-docosahexaenoic acid
0.0012 - 0.039
cis-5,8,11,14,17-eicosapentaenoic acid
0.0017 - 0.013
cis-5,8,11,14-eicosatetraenoic acid
0.0027 - 0.061
cis-7,10,13,16-docosatetraenoic acid
0.002 - 0.036
cis-8,11,14-eicosatrienoic acid
0.0048 - 0.162
gamma-linolenic acid
0.08 - 0.29
guaiacol
1.3 - 5.5
H2O2
0.0055 - 0.0068
linoleic acid
0.0083 - 0.0854
N,N,N',N'-tetramethyl-p-phenylenediamine
0.005 - 0.011
O2
0.02 - 0.437
trans-5-phenyl-4-pentenyl-1-hydroperoxide
additional information
additional information
-
top print hide
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3.45
(4Z,7Z,10Z,13Z,16Z,19Z)-Docosahexaenoic acid
Mus musculus
Q05769
pH 8.0, 25°C, COX-2 mutant N580A
8.7
(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoic acid
Mus musculus
Q05769
pH 8.0, 25°C, COX-2 mutant N580A
27
arachidonate
Mus musculus
Q05769
pH 8.0, 25°C, COX-2 mutant N580A
top print hide
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
9
(4Z,7Z,10Z,13Z,16Z,19Z)-Docosahexaenoic acid
Mus musculus
Q05769
pH 8.0, 25°C, COX-2 mutant N580A
40206
920
(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoic acid
Mus musculus
Q05769
pH 8.0, 25°C, COX-2 mutant N580A
41642
5240
arachidonate
Mus musculus
Q05769
pH 8.0, 25°C, COX-2 mutant N580A
619
top print hide
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.005
indomethacin
-
-
0.00027 - 0.001
nimesulide
additional information
additional information
-
top print hide
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.003 - 0.0212
alpha-linolenic acid
0.0008 - 0.0009
indomethacin
0.0026 - 0.0198
linoleic acid
0.0026 - 0.0507
NS-398
0.1226 - 0.1245
oleic acid
0.0186 - 0.0388
peroxynitrite
0.018 - 0.086
quercetin
top print hide
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0027
-
mutant Y348F, cyclooxygenase activity
0.0039
-
mutant Y504F, cyclooxygenase activity
0.0047
-
mutant Y348F/Y504F, cyclooxygenase activity
0.0058
-
wild-type, cyclooxygenase activity
2.4
-
prostaglandin H1 synthesis
2300
cyclooxygenase activity for partially purified prostaglandin H synthase 1 of Salvelinus fontinalis, tPGHS-1
4220
-
purified recombinant His6-tagged PGHS-2, pH 8.0, 37°C
15000
cyclooxygenase activity for partially purified prostaglandin H synthase 2 of Salvelinus fontinalis, tPGHS-2
top print hide
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 7.3
-
formation of prostaglandin E2 from arachidonic acid
7.5 - 8
-
formation of prostaglandin F2alpha
7.8
-
enzyme-linked immunoassay for PGE2
8 - 8.5
-
formation of prostaglandin E2 and D2
8.1
-
assay at
top print hide
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 9
-
about 70% of maximum activity at pH 6.0 and 9.0 of prostaglandin E2 formation, about 50% of maximum activity at pH 6.0 and 9.0 of prostaglandin F2alpha formation
7.2 - 9
-
about 60% of maximum activity at pH 7.2 and 9.0 of prostaglandin D2 formation
top print hide
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
top print hide
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 30
top print hide
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
seminal plasma induces and potentiates the expression of PTGS2 in cervicovaginal cells and tissues
Manually annotated by BRENDA team
endometrial stromal cells
Manually annotated by BRENDA team
-
caput and cauda
Manually annotated by BRENDA team
fetal; fetal
Manually annotated by BRENDA team
PTGS2, during early, mid, and late stages
Manually annotated by BRENDA team
-
isozyme 2
Manually annotated by BRENDA team
-
increased expression of PTGS2
Manually annotated by BRENDA team
-
human neuroblastoma cell
Manually annotated by BRENDA team
-
somatic and spermatogenic cells
Manually annotated by BRENDA team
-
vaginal cell line, expression of prostaglandin-endoperoxide synthase 2, i.e. cyclooxygenase 2, in human vaginal cells in response to toll-like receptor ligands and other proinflammatory stimuli, such vaginal mucosal irritant nonoxynol-9, in a synergistic manner
Manually annotated by BRENDA team
additional information
top print hide
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
probably associated with
-
Manually annotated by BRENDA team
additional information
top print hide
PDB
SCOP
CATH
ORGANISM
UNIPROT
top print hide
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
63500
4 * 63500, recombinant His-tagged enzyme, SDS-PAGE
65000
-
immunoblot
65620
-
amino acid sequence deduced from nucleotide sequence of cDNA, MW of unglycosylated enzyme
73000
-
determined by SDS-PAGE and immunoblotting
75000
-
x * 75000, SDS-PAGE, isozyme 1 and 2
300000 - 350000
-
gel filtration
330000
about, recombinant His-tagged enzyme, gel filtration
top print hide
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
tetramer
4 * 63500, recombinant His-tagged enzyme, SDS-PAGE
additional information
top print hide
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
top print hide
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid bound to Co3+-protoporphyrin IX-reconstituted recombinant His-tagged isozyme COX-2 mutant N580A, 0.003 ml of 3 mg/ml protein in 25 mM Tris, pH 8.0, 150 mM NaCl, and 0.53% w/v beta-octylglucoside is mixed with 0.003 ml of reservoir solution containing 23-34% polyacrylic acid 5100, 100 mM HEPES, pH 7.5, 20 mM MgCl2, and 0.6% w/v beta-octylglucoside, equilibration over reservoir solution without beta-octylglucoside, 23°C, 3 days to 4 weeks, X-ray diffraction structure determination and analysis at 2.1 A, 2.4 A, and 2.65 A resolution, respectively
hanging-drop vapor-diffusion method, 2.0 A resolution X-ray crystal structure of the prostaglandin H2 synthase-1 in complex with alpha-methyl-4-biphenylacetic acid, a defluorinated analog of the steroidal anti.inflammatory drug flurbiproten
-
the 2.0 A resolution crystal structure of the MnIII form of ovine prostaglandin H2 synthase-1 is described
-
top print hide
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 8
-
24°C, 5 min, stable
438375
top print hide
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
-
pH 8.0, 5 min, stable
50
-
pH 8.0, 5 min, complete loss of activity
top print hide
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
diethyldithiocarbamate stabilizes
-
ethylene glycol stabilizes
-
flufenamate stabilizes
-
glycerol stabilizes
-
PGH-synthase immobilized on dry Opuntia imbricata trunk retains around 30-40% of initial activity, immobilized microsomes are able to catalyze several cycles of arachidonic acid transformation and are more stable than free enzyme solution upon storage at 4°C
-
top print hide
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4°C, Opuntia imbricata-immobilized enzyme, 2 days, 90-95% loss of initial activity
-
4°C, Opuntia imbricata-immobilized enzyme, 24 h, 36-48% of initial activity is maintained after storage
-
4°C, Opuntia imbricata-immobilized enzyme, 4 days, complete loss of activity
-
top print hide
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
N-octyl-beta-D-glucopyranoside, Tween-20, CHAPS, and maltoside are used for solubilization of prostaglandin H2 synthase-1, frozen microsomal extracts are thawed and purified using a fast-flow DEAE-Sepharose and a S-300 column
-
recombinant C-terminally or N-terminally His6-tagged PGHS-2 from Pichia pastoris strain GS115 microsomes by ultracentrifugation, nickel affinity and anion exchange chromatography, purification of the C-terminally His6 tagged hPGHS-2 is more efficient, relative efficiency of the detergents used for solubilization of the recombinant hPGHS-2, CHAPS is most effective, method evaluation, overview
-
recombinant enzyme, apoenzyme
-
recombinant His-tagged enzyme 138fold from Escherichia coli strain BL21(DE3)RP membranes by nickel affinity chromatography, and anion exchange chromatography
recombinant His-tagged wild-type and mutant COX-2 proteins by nickel affinity chromatography and gel filtration
recombinant protein expressed in Sf9 cells, protein is purified from the membrane fraction using a High Q ion exchange column; recombinant protein expressed in Sf9 cells, protein is purified from the membrane fraction using a High Q ion exchange column
recombinant protein expressed in Sf9 cells; recombinant protein expressed in Sf9 cells
the apo form of ovine PGHS isoform-1 is purified from ram seminal vesicles, the holoenzyme is reconstituted by adding MnIII-PPIX to the enzyme
-
using nickel affinity chromatography
-
top print hide
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
all mutants are overexpressed in the baculovirus system as detergent-soluble full-length proteins
-
codes for protein of 604 amino acids, 89% identity to human protein
-
COX-1b, expression in COS-7 cells
-
expressed in colon carcinoma cells COLO320DM; expressed in colon carcinoma cells COLO320DM
-
expressed in COS-1 cells; into the mammalian expression vector pcDNA3
-
expression in Spodoptera frugiperda Sf-9 cells; expression in Spodoptera frugiperda Sf-9 cells; into a pVL1392 vector for transformation of Escherichia coli DH5alpha competent cells; into a pVL1392 vector for transformation of Escherichia coli DH5alpha competent cells
expression of His-tagged wild-type and mutant COX-2 proteins
expression of isozymes PHS-1 and PHS-2 in CHO-K1 cells
-
expression of mutant enzymes in Sf9 cells
-
for transfection of COS-7 cells
-
functional expression of C-terminally or N-terminally His6-tagged and non-tagged PGHS-2 in Pichia pastoris strain GS115, GS117 and KM71 using native or yeast signal sequences, method evaluation by enzyme activity, overview
-
into a baculoviral vector for expression in Sf-21 cells
-
into the pVL1393 vector
-
isozymes 1 and 2
-
PGHS DNA and amiino acid sequence determination and analysis, sequence comparisons
PGHS DNA and amino acid sequence determination and analysis, sequence comparisons, functional expression of His-tagged enzyme in Escherichia coli strain BL21(DE3)RP
quantitative real-time RT-PCR enzyme expression analysis
-
quantitative RT-PCR enzyme expression analysis
-
stable expression of PHS-1 and PHS-2 in CHO-K1 cells
-
top print hide
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
0.1 and 0.001 mM lysophosphatidic acid increases PTGS2 mRNA abundance in the uterine endometrium, the lysophosphatidic acid-induced increase of PTGS2 expression is reduced by cotreatment with Ki-16425
-
brainstem PGHS-1 exhibits robust increases in mRNA postpartum, cerebellar PGHS-1 mRNA is upregulated at 120 days of gestational age; the hippocampus exhibits increases in PGHS-2 mRNA after 80 days of gestational age, brainstem and cortex PGHS-2 exhibit robust increases in mRNA postpartum, cerebellar PGHS-2 mRNA is upregulated at 120 days of gestational age
-
isozyme Ptgs2 transcript level significantly increases at 2 and 4 h after the deciduogenic stimulus with sesame oil is given, and the levels return to prestimulated levels at 8, 16, and 32 h. In contrast to isoform PTGS1 protein levels, PTGS2 protein is significantly higher at 8 h and remains elevated at 16 and 32 h. PTGS2 protein levels are significantly higher in stimulated endometrium at 8 and 32 h than in nonstimulated endometrium
-
luteinized hormone induces prostaglandin-endoperoxide synthase 2 expression in periovulatory granulosa cells, the induction in part results from Runt-related transcription factor 1-mediated transactivation of the Ptgs2 promoter
-
seminal plasma induces prostaglandin-endoperoxide synthase 2 expression in immortalized human vaginal cells, involvement of semen prostaglandin E2 in PTGS2 upregulation. Expression of prostaglandin-endoperoxide synthase 2, i.e. cyclooxygenase 2, in human vaginal cells in response to toll-like receptor ligands and other proinflammatory stimuli. Seminal prostaglandin-E2 is one of the major factors in PTGS2 induction
-
the hippocampus exhibits decreases in PGHS-1 mRNA after 80 days of gestational age
-
transplantation of hepatocytes induces hepatic expression of prostaglandin-endoperoxide synthase isoform 1 (5fold); transplantation of hepatocytes induces hepatic expression of prostaglandin-endoperoxide synthase isoform 2 (2.8fold)
-
when NCI-H292 cells are transfected with E2F1 siRNA, PTGS2 expression is attenuated
-
top print hide
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C299S/C526S
-
mutant, relative activity: 70%
cyclooxygenase-1bdeltaG
-
mutant, in which the frame shift in the splice variant human cyclooxygenase-1b is corrected
E488G
-
site-directed mutagenesis, the mutant shows reduced sensitivity to the cyclooxygenase inhibitor nimesulide compared to the wild-type enzyme. The activity with eicosapentaenoate is altered
F59C
-
mutant, relative activity: 50%
F66C
-
mutant, relative activity: 50%
F84C
-
mutant, relative activity: 50%
G587R
-
site-directed mutagenesis, the mutant shows reduced sensitivity to the cyclooxygenase inhibitor nimesulide compared to the wild-type enzyme. The activity with eicosapentaenoate is not affected
G83C
-
mutant, relative activity: 35%
H75C
-
mutant, relative activity: 70%
I63C
-
mutant, relative activity: 70%
I77C
-
mutant, relative activity: 60%
K211A
-
complete abolition of activity
K211A/K215A
-
complete abolition of activity
K211A/K215A/K222A
-
complete abolition of activity
K211A/K222A
-
complete abolition of activity
K211E
-
complete abolition of activity
K211E/K215E
-
complete abolition of activity
K211E/K215E/K222E
-
complete abolition of activity
K211E/K222E
-
complete abolition of activity
K215A
-
does not impair PGHS activity
K215A/K222A
-
significant reduction of 27% of the activity
K215E
-
does not impair PGHS activity
K215E/K222E
-
significant reduction of 58% of the activity
K222A
-
no significant reduction of activity
K222E
-
no significant reduction of activity
K64C
-
mutant, relative activity: 70%
L60C
-
mutant, relative activity: 70%
L65C
-
mutant, relative activity: 70%
L67C
-
mutant, relative activity: 40%
L78C
-
mutant, relative activity: 30%
N382A
-
mutation has little effect on the cyclooxygenase specific activity or activation efficiency but almost doubles the cyclooxygenase catalytic output before self-inactivation
N382D
-
mutation has little effect on the cyclooxygenase specific activity or activation efficiency but almost doubles the cyclooxygenase catalytic output before self-inactivation
N382L
-
mutation has little effect on the cyclooxygenase specific activity or activation efficiency but almost doubles the cyclooxygenase catalytic output before self-inactivation
N72C
-
mutant, relative activity: 60%
N86C
-
mutant, relative activity: 50%
N89C
-
mutant, relative activity: 30%
N90C
-
mutant, relative activity: 20%
R228H
-
site-directed mutagenesis, the mutant shows reduced sensitivity to the cyclooxygenase inhibitor nimesulide compared to the wild-type enzyme. The activity with eicosapentaenoate is not affected
R62C
-
mutant, relative activity: 50%
S516M
-
mutation mimics acetylation of Ser516, mutant still sensitive to most inhibitors, not: diclofenac, meclofenamic acid
T61C
-
mutant, relative activity: 60%
T73C
-
mutant, relative activity: 40%
V511A
-
site-directed mutagenesis, the mutant shows reduced sensitivity to the cyclooxygenase inhibitor nimesulide compared to the wild-type enzyme. The activity with eicosapentaenoate altered
V74C
-
mutant, relative activity: 60%
V87C
-
mutant, relative activity: 30%
V88C
-
mutant, relative activity: 30%
W85C
-
mutant, relative activity: 10%
Y148F
-
mutant enzyme has cyclooxygenase activity comparable to that of the native enzyme
Y148F/Y348F/Y385F/Y404F/Y504F
-
no cyclooxygenase activity detected
Y148F/Y348F/Y404F/Y504F
-
mutant enzyme has specific cyclooxygenase activity approximately half that of native enzyme. Modest increase in cyclooxygenase self-inactivation rate, 2.3fold
Y348F/Y504F
-
mutant
Y385F
-
no cyclooxygenase activity detected
Y404F
-
mutant enzyme has cyclooxygenase activity comparable to that of the native enzyme. Modest increase in cyclooxygenase self-inactivation rate, 2.3fold
Y76C
-
mutant, relative activity: 70%
L531A
site-directed mutagenesis, the mutant shows reduced Vmax and Km with arachidonate compared to the wild-type COX-2
L531F
site-directed mutagenesis, the mutant shows reduced Vmax and Km with arachidonate compared to the wild-type COX-2
L531P
site-directed mutagenesis, the mutant shows reduced Vmax and Km with arachidonate compared to the wild-type COX-2
L531T
site-directed mutagenesis, the mutant shows reduced Vmax and Km with arachidonate compared to the wild-type COX-2
N580A
site-directed mutagenesis, crystal structure determination with bound substrates, overview
Arg120Glu
-
Arg120 important for interaction with substrate and with inhibitors containing a free carboxylic acid moiety
Cys313Ser
-
cyclooxygenase and peroxidase activity reduced by 80-90%, no significant effect on inhibition, dimer formation, glycosylation
Cys540Ser
-
cyclooxygenase and peroxidase activity reduced by 80-90%, no significant effect on inhibition, dimer formation, glycosylation
top print hide
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
the purified recombinant apoenzyme is reconstituted with Co3+-protoporphyrin IX and fatty acid substrate to generate the appropriate enzyme-substrate complexes for X-ray crystallographic analyses
top print hide
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
top
Show AA Sequence (102 entries)
Please use the Sequence Search for a specific query.
top
Show Disease (23994 entries)
Longer loading times are possible.
top
top
LINKS TO OTHER DATABASES (specific for EC-Number 1.14.99.1)
ExplorEnz
ExPASy
KEGG
MetaCyc
SABIO-RK
NCBI: PubMed, Protein, Nucleotide, Structure, Genome, OMIM
IUBMB Enzyme Nomenclature
PROSITE Database of protein families and domains
SYSTERS
Protein Mutant Database
InterPro (database of protein families, domains and functional sites)