Information on EC 1.14.99.1 - prostaglandin-endoperoxide synthase

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The expected taxonomic range for this enzyme is: Eukaryota

EC NUMBER
COMMENTARY
1.14.99.1
-
RECOMMENDED NAME
GeneOntology No.
prostaglandin-endoperoxide synthase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
arachidonate + AH2 + 2 O2 = prostaglandin H2 + A + H2O
show the reaction diagram
mechanism, enzyme acts both as dioxygenase and as peroxidase
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Arachidonic acid metabolism
-
-
arachidonic acid metabolism
-
-
C20 prostanoid biosynthesis
-
-
Metabolic pathways
-
-
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.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
(PG)H synthase
-
-
-
-
cyclooxygenase
-
-
-
-
fatty acid cyclooxygenase
-
-
-
-
PG synthetase
-
-
-
-
prostaglandin endoperoxide synthetase
-
-
-
-
prostaglandin G/H synthase
-
-
-
-
prostaglandin synthase
-
-
-
-
prostaglandin synthase-2
-
-
-
-
prostaglandin synthetase
-
-
-
-
synthase, prostaglandin
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
39391-18-9
-
9055-65-6
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Holstein-Friesian cow
UniProt
Manually annotated by BRENDA team
overview
-
-
Manually annotated by BRENDA team
prostatic epithelial cell line
-
-
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
a homology modeling structure of human PGHS-1 is constructed using the Swiss-Model server and the ovine crystal structure 1Q4G as template
-
-
Manually annotated by BRENDA team
isozyme PGHS-1
SwissProt
Manually annotated by BRENDA team
isozyme PGHS-2
SwissProt
Manually annotated by BRENDA team
overview
-
-
Manually annotated by BRENDA team
PGHS-1
SwissProt
Manually annotated by BRENDA team
PGHS-2
SwissProt
Manually annotated by BRENDA team
recombinant enzyme, product of COX-2
-
-
Manually annotated by BRENDA team
recombinant isozymes 1 and 2
-
-
Manually annotated by BRENDA team
rhesus monkey
-
-
Manually annotated by BRENDA team
recombinant enzyme
-
-
Manually annotated by BRENDA team
isozymes PHS-1 and PHS-2
-
-
Manually annotated by BRENDA team
male
-
-
Manually annotated by BRENDA team
PGHS-1
SwissProt
Manually annotated by BRENDA team
PGHS-1 precursor
SwissProt
Manually annotated by BRENDA team
PGHS-2
SwissProt
Manually annotated by BRENDA team
PGHS-2 precursor
SwissProt
Manually annotated by BRENDA team
recombinant enzyme
-
-
Manually annotated by BRENDA team
Sprague-Dawley rat
-
-
Manually annotated by BRENDA team
squirrel monkey
-
-
Manually annotated by BRENDA team
brook trout, isozymes 1 and 2
-
-
Manually annotated by BRENDA team
overview
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
I6VVK9
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
P23219, P35354
PGHS-1 inhibition in activated human plateletts significantly decreases PGHS-1-dependent thromboxane B2 formation in parallel with a decrease in platelet aggregation
metabolism
-
the enzyme catalyzes the committed step in prostaglandin biosynthesis
physiological function
-
periovulatory expression of the Ptgs2 gene is essential for ovulation
physiological function
-
PGHS is involved in inflammation processes
physiological function
-
PGHS-2 also shows cyclooxygenase activity, which is implicated in colorectal cancer
physiological function
-
PHS isozyme-dependent oxidative damage to proteins and DNA, and cytotoxicity, overview. hPHS-1- and hPHS-2-expressing cells incubated with dopamine, L-dihydroxyphenylalanine, dihydroxyphenylacetic acid, or homovanillic acid exhibit increased cytotoxicity compared to untransfected cells, and cytotoxicity is increased further by exogenous arachidonic acid, which increases hPHS activity. Isozyme-specific, PHS-dependent oxidative damage and cytotoxicity caused by neurotransmitters, their precursors, and their metabolites may contribute to neurodegeneration associated with aging
physiological function
-
prostaglandin H synthases or cyclooxygenases catalyse the peroxidation of arachidonic acid to PGG2 and PGH2 which are further converted to a series of prostaglandins and thromboxane A2. The enzyme catalyzes formation of oxidative stress biomarkers malondialdehyde and 15(S)-8-iso-prostaglandin F2alpha, and other F2-isoprostanes, promoted by glutathione
physiological function
-
prostaglandin-endoperoxide synthases and nitric oxide synthases regulate the bovine corpea lutea life span mainly during the transition from the luteotrophic to the luteolytic phase
physiological function
-
PTGS2 plays a pivotal role in inflammation, tissue damage, and tumorigenesis. Differential regulation of PCSKs by PTGS2 with a pivotal role for E2F1, implication of PTGS2-derived PGE2 as a determining factor in the regulation of PCSK activity
metabolism
-
prostaglandin H synthase-1 catalyzes the first two steps in prostaglandin synthesis, prostaglandin H synthase-2 catalyzes the first two steps in prostaglandin synthesis
additional information
-
aqueous extracts of Chromoleana odorata, commonly used in traditional medicine as antiinflammatory drug against pains or as cataplasm to stop hemorrhage in Ivory Coast, the essential oil extracted from the fresh leaves activates the cyclooxygenase activity of the PGHS, overview
additional information
-
neurotoxicity of the amphetamine analogues methamphetamine and 3,4-methylenedioxyamphetamine, the active metabolite of ecstasy, may involve their prostaglandin H synthase-dependent bioactivation to free radical intermediates that generate reactive oxygen species and oxidatively damage cellular macromolecules. The activation effect is blocked by irreversible enzyme inhibitor acetylsalicylic acid, overview
additional information
-
PHS is involved in the mechanism of thalidomide to cause increased embryonic DNA oxidation measured as 8-oxoguanine leading to embryopathies, phenotype, overview. A prostaglandin H synthase-dependent, reactive oxygen species-mediated mechanism. Thalidomide teratogenicity was blocked by maternal pretreatment with acetylsalicylic acid, an irreversible inhibitor of prostaglandin H synthase
additional information
-
seminal plasma-induced PTGS2 expression is mediated by intracellular signaling pathways involving MAPKs and NF-kappaB. Depending on cell type and stimulus, different intracellular signaling pathways are involved in inflammation and PTGS2 expression
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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
-
-
-
-
-
(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoic acid + AH2 + O2
? + A + H2O
show the reaction diagram
Q9PTN3, Q9PW89
-
-
-
-
(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoic acid + AH2 + O2
? + A + H2O
show the reaction diagram
Q05769
the substrate is bound in the cyclooxygenase channel of COX-2, binding structure, overview. The carboxylate of docosahexaenoate interacts with Arg120 and Tyr355 at the base of the channel and the omega-end abuts the side chain of Ile377 near Gly533 in the hydrophobic groove above Ser530
-
-
?
(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoic acid + AH2 + O2
? + A + H2O
show the reaction diagram
Q05769
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 G1 + ?
show the reaction diagram
-
bis-dioxygenase activity, cyclooxygenase activity, presence of hematin
9alpha,11alpha-epidioxy-15(S)-hydroperoxy-13-trans-prostenoic acid
?
8,11,14-eicosatrienoic acid + O2
prostaglandin H1 + ?
show the reaction diagram
-
-
-
-
-
8,11,14-eicosatrienoic acid + O2
prostaglandin H1 + ?
show the reaction diagram
-
hydroperoxidase activity, presence of hematin and tryptophan
-
-
?
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 G2 + A + H2O
show the reaction diagram
I6VVK9
-
-
-
?
arachidonate + AH2 + 2 O2
prostaglandin H2 + A + H2O
show the reaction diagram
-
-
-
-
?
arachidonate + AH2 + 2 O2
prostaglandin H2 + A + H2O
show the reaction diagram
P23219, P35354
-
-
-
?
arachidonate + AH2 + 2 O2
prostaglandin H2 + A + H2O
show the reaction diagram
-
-
-
-
?
arachidonate + AH2 + 2 O2
prostaglandin H2 + A + H2O
show the reaction diagram
I6VVK9
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
-
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
-
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
P35354
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
-
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
-
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
-
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
-
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
-
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
P23219, P35354
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
P05979, P79208
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
P05979, P79208
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
Q9PTN3, Q9PW89
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
P35355
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
Q05769
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
P23219
the reaction comprises two steps: dioxygenation of arachidonate to yield prostaglandin G2 containing both a 9-11 endoperoxide and a 15-peroxide group, and a peroxidase reaction, which converts prostaglandin G2 to prostaglandin H2 where the 15-peroxide is reduced to an alcohol
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
P05979
the reaction comprises two steps: dioxygenation of arachidonate to yield prostaglandin G2 containing both a 9-11 endoperoxide and a 15-peroxide group, and a peroxidase reaction, which converts prostaglandin G2 to prostaglandin H2 where the 15-peroxide is reduced to an alcohol
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
Q05769
substrate binding structure and nonproductive conformation, overview
-
-
?
arachidonate + electron donor + O2
prostaglandin H2 + oxidized electron donor + H2O
show the reaction diagram
-
-
-
-
?
arachidonate + electron donor + O2
prostaglandin H2 + oxidized electron donor + H2O
show the reaction diagram
-
-
-
-
?
arachidonate + electron donor + O2
prostaglandin H2 + oxidized electron donor + H2O
show the reaction diagram
-
-
-
-
?
arachidonate + electron donor + O2
prostaglandin H2 + oxidized electron donor + H2O
show the reaction diagram
-
-
-
-
?
arachidonate + electron donor + O2
prostaglandin H2 + oxidized electron donor + H2O
show the reaction diagram
-
-
-
-
?
arachidonate + electron donor + O2
prostaglandin H2 + oxidized electron donor + H2O
show the reaction diagram
-
cyclooxygenase activity
-
-
?
arachidonate + reduced N,N,N',N'-tetramethylphenylenediamine + 2 O2
prostaglandin G2 + oxidized N,N,N',N'-tetramethylphenylenediamine + H2O
show the reaction diagram
I6VVK9
-
-
-
?
arachidonate + reduced N,N,N',N'-tetramethylphenylenediamine + 2 O2
prostaglandin H2 + oxidized N,N,N',N'-tetramethylphenylenediamine + H2O
show the reaction diagram
P23219, P35354
-
-
-
?
arachidonate + reduced N,N,N',N'-tetramethylphenylenediamine + 2 O2
prostaglandin H2 + 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
I6VVK9
-
-
-
?
arachidonic acid + 2 O2
prostaglandin G2
show the reaction diagram
P05979, P79208
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-hydroperoxy-9alpha,11alpha-peroxiprosta-5,13-dienoic acid + A + ?
show the reaction diagram
-
-
-
?
arachidonic acid + AH2 + 2 O2
prostaglandin E2 + A + ?
show the reaction diagram
-
-
-
?
arachidonic acid + AH2 + 2 O2
15(R)-hydroxy-eicosatetraenoic acid + A + ?
show the reaction diagram
-
-
product of aspirin treated enzyme
?
arachidonic acid + AH2 + 2 O2
15(R)-hydroxy-eicosatetraenoic acid + A + ?
show the reaction diagram
-
-
product of aspirin acetylated enzyme or S516M mutant
?
arachidonic acid + AH2 + 2 O2
6-keto-prostaglandin F1alpha + A + ?
show the reaction diagram
-
activity assay
-
-
?
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
P23219, P35354
-
-
-
?
cis-4,7,10,13,16,19-docosahexaenoic acid + AH2 + O2
?
show the reaction diagram
P23219, P35354
-
-
-
?
cis-5,8,11,14,17-eicosapentaenoic acid + AH2 + O2
?
show the reaction diagram
P23219, P35354
-
-
-
?
cis-5,8,11,14-eicosatetraenoic acid + AH2 + O2
?
show the reaction diagram
P23219, P35354
-
-
-
?
cis-7,10,13,16-docosatetraenoic acid + AH2 + O2
?
show the reaction diagram
P23219, P35354
-
-
-
?
cis-8,11,14-eicosatrienoic acid + AH2 + O2
?
show the reaction diagram
P23219, P35354
-
-
-
?
gamma-linolenic acid + AH2 + O2
?
show the reaction diagram
P23219, P35354
-
-
-
?
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
-
-
-
-
?
prostaglandin G2 + AH2
prostaglandin H2 + A + H2O
show the reaction diagram
-
-
-
-
?
linolenic acid + AH2 + O2
?
show the reaction diagram
P23219, P35354
-
-
-
?
additional information
?
-
-
-
-
-
-
additional information
?
-
-
electron donors used by hydroperoxidase: phenylbutazone, sulindac
-
-
-
additional information
?
-
-
electron donors used by hydroperoxidase: phenylbutazone, sulindac
-
-
-
additional information
?
-
-
formation of prostaglandin E2, prostaglandin F2alpha and prostaglandin D2 from arachidonic acid
-
-
-
additional information
?
-
-
xenobiotics such as benzo(a)pyrene cannot act as electron donor, but undergo cooxydation during hydroperoxidase reaction
-
-
-
additional information
?
-
-
functional differentiation of cyclooxygenase and peroxidase activities by trypsin treatment
-
-
-
additional information
?
-
-
cooxidation of: 4-chloroaniline to yield N-(4-chlorophenyl)-hydroxylamine and 1-chloro-4-nitrosobenzene
-
-
-
additional information
?
-
-
major products of arachidonic acids are prostaglandins D2 and E2, minor products prostaglandin F2alpha and 6-keto-prostaglandin F1alpha
-
-
-
additional information
?
-
-
relative activities of isozymes 1,2 depend on source of arachidonic acid - exogenous versus endogenous
-
-
-
additional information
?
-
-
also catalyzed: transformation of arachidonic acid into prostaglandin E2, prostaglandin F2 alpha and 12-hydroxy-5,8,10-heptadecatrienoic acid
-
-
-
additional information
?
-
-
first step in prostaglandin synthesis
-
-
-
additional information
?
-
-
enzyme has a central position in prostanoic metabolism: first step in formation of prostaglandins and thromboxanes, the conversion of arachidonic acid to prostaglandin endoperoxides G and H
-
-
-
additional information
?
-
-
the expression of PGHS-2 may be involved in inhibiting progesterone production
-
-
-
additional information
?
-
P79208
prostaglandin synthesis within the fetal central nervous system is critical for the the modulation of hypotension-induced fetal ACTH secretion involving PGHS-2, overview
-
-
-
additional information
?
-
-
dopamine precursor L-dihydroxyphenylalanine, i.e. L-DOPA, and metabolites dihydroxyphenylacetic acid, homovanillic acid, and 3-methoxytyramine may serve as substrates for prostaglandin H synthase-catalyzed bioactivation to free radical intermediates
-
-
-
additional information
?
-
-
PGHS-2 also shows cyclooxygenase activity
-
-
-
additional information
?
-
Q05769
although arachidonic acid is the preferred substrate, other fatty acids are oxygenated by the isozymes with varying efficiencies. The substrates bind in different conformations in each monomer constituting the homodimer in their respective structures such that one monomer exhibits nonproductive binding and the other productive binding of the substrate in the cyclooxygenase channel, Arg120 and Leu531 play a role, overview
-
-
-
additional information
?
-
-
maximal values of the initial reaction rate and yield of the product are attained at oxygen concentration 0.05 mM
-
-
-
additional information
?
-
-
activity with arachidonate in presence of glutathione leads to formation of malondialdehyde and (15S)-8-iso-prostaglandin F2alpha
-
-
-
additional information
?
-
P23219, P35354
PGHS-1 also exhibits peroxidase activity
-
-
-
additional information
?
-
P23219, P35354
PGHS-2 also exhibits peroxidase activity
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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 G2 + A + H2O
show the reaction diagram
I6VVK9
-
-
-
?
arachidonate + AH2 + 2 O2
prostaglandin H2 + A + H2O
show the reaction diagram
-
-
-
-
?
arachidonate + AH2 + 2 O2
prostaglandin H2 + A + H2O
show the reaction diagram
P23219, P35354
-
-
-
?
arachidonate + AH2 + 2 O2
prostaglandin H2 + A + H2O
show the reaction diagram
-
-
-
-
?
arachidonate + AH2 + 2 O2
prostaglandin H2 + A + H2O
show the reaction diagram
I6VVK9
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
-
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
-
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
P35354
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
-
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
-
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
-
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
P23219, P35354
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
P05979, P79208
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
P05979, P79208
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
Q9PTN3, Q9PW89
-
-
-
?
prostaglandin G2 + AH2
prostaglandin H2 + A + H2O
show the reaction diagram
-
-
-
-
?
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
Q05769
-
-
-
?
additional information
?
-
-
first step in prostaglandin synthesis
-
-
-
additional information
?
-
-
enzyme has a central position in prostanoic metabolism: first step in formation of prostaglandins and thromboxanes, the conversion of arachidonic acid to prostaglandin endoperoxides G and H
-
-
-
additional information
?
-
-
the expression of PGHS-2 may be involved in inhibiting progesterone production
-
-
-
additional information
?
-
P79208
prostaglandin synthesis within the fetal central nervous system is critical for the the modulation of hypotension-induced fetal ACTH secretion involving PGHS-2, overview
-
-
-
additional information
?
-
-
dopamine precursor L-dihydroxyphenylalanine, i.e. L-DOPA, and metabolites dihydroxyphenylacetic acid, homovanillic acid, and 3-methoxytyramine may serve as substrates for prostaglandin H synthase-catalyzed bioactivation to free radical intermediates
-
-
-
additional information
?
-
-
PGHS-2 also shows cyclooxygenase activity
-
-
-
additional information
?
-
-
activity with arachidonate in presence of glutathione leads to formation of malondialdehyde and (15S)-8-iso-prostaglandin F2alpha
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Hematin
-
;
heme
-
enzyme contains a heme group
heme
-
either free or protein-bound heme is required for cyclooxygenase- and hydroperoxidase activity
heme
-
hemin and hematin
heme
-
;
heme
-
-
heme
Q05769
-
heme
I6VVK9
ferric heme, heme content of the purified recombinant GvPGHS determined by a pyridine-hemochromogen assay is 0.39 mol of heme/mol of GvPGHS monomer
iron-protoporphyrin IX
P23219, P35354
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
-
epinephrine-hydrogentartrate can serve as cofactor; epinephrine-hydrogentartrate can servve as cofactor
-
additional information
-
peroxidase activity of PGHS requires reducing co-substrates as electron donors; peroxidase activity of PGHS requires reducing co-substrates as electron donors
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe2+
I6VVK9
ferric heme enzyme
Fe3+
-
-
Fe3+
-
-
Iron
-
possibly contains heme and non-heme iron
Iron
P23219, P35354
each subunit contains a molecule of Fe3+-protoporphyrin IX noncovalently attached to the enzyme, the heme group is essential for both enzyme activities, the cofactor is released by induction of inhibitor nitroarachidonic acid; each subunit contains a molecule of Fe3+-protoporphyrin IX noncovalently attached to the enzyme, the heme group is essential for both enzyme activities, the cofactor is released by induction of inhibitor nitroarachidonic acid
Mn3+
-
substitution of ferric heme by MnIII protoporphyrin IX greatly diminishes the peroxidase activity, but has little effect on the cyclooxygenase activity
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
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
P23219, P35354
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
P23219, P35354
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
P23219, P35354
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
-
complete inhibition at 0.04 mM
5,8,11,14-Eicosatetraynoic acid
-
-
5-bromo-2-[4-fluorophenyl]-3-[4-methylsulfonylphenyl]-thiophene
-
DuP-697, selective for isozyme 2
5-bromo-2-[4-fluorophenyl]-3-[4-methylsulfonylphenyl]-thiophene
-
50% inhibition at 8.7 nM
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
P23219, P35354
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
-
inhibition of prostaglandin G1 synthesis
Acetylsalicylic acid
-
inhibition of oxygenase activity by acetylating a serine residue of the enzyme
Acetylsalicylic acid
-
isozyme 1, complete inhibition, isozyme 2, change in reaction, main product from arachidonate is 15-hydroxyeicosatetraenoic acid
Acetylsalicylic acid
-
-
Acetylsalicylic acid
-
irreversible inhibitor
Acetylsalicylic acid
-
an irreversible inhibitor of both hPHS-1 and hPHS-2
Albumin
-
-
-
Albumin
-
bovine serum albumin inhibits by binding of arachidonic acid
-
alpha-linolenic acid
-
;
anilorac
-
isozyme 1, 50% inhibition at 0.0007 mM, isozyme 2, 50% inhibition at 0.009 mM
-
aspirin
-
cyclooxygenase activity
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
-
recombinant protein, 50% inhibition at 0.04 mM
diclofenac
-
50% inhibition at 9.4 nM
diclofenac
-
isozyme 1, 50% inhibition at 0.0009 mM, isozyme 2, 50% inhibition at 0.0015 mM
diclofenac
-
isozyme 1, 50% inhibition at 0.0003 mM, isozyme 2, 50% inhibition at 18 nM
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
-
a standard PHS-2 inhibitor
DUP-697
-
a PHS-2-specific inhibitor
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
-
isozyme 1, 50% inhibition at 40 nM, isozyme 2, 50% inhibition at 500 nM
Flurbiprofen
-
isozyme 1, 50% inhibition at 0.0009 mM, isozyme 2, 50% inhibition at 0.0009 mM
Flurbiprofen
-
isozyme 1, 50% inhibition at 0.0005 mM, isozyme 2, 50% inhibition at 0.003 mM
Flurbiprofen
-
cyclooxygenase inhibitor
Haptoglobin
-
-
-
Human serum
-
-
-
Ibuprofen
-
recombinant protein, 50% inhibition at 0.04 mM
Ibuprofen
-
reversible
Ibuprofen
-
50% inhibition at 0.253 mM
Ibuprofen
-
isozyme 1, 50% inhibition at 0.0026 mM, isozyme 2, 50% inhibition at 0.0015 mM
Ibuprofen
-
isozyme 1, 50% inhibition at 0.009 mM, isozyme 2, 50% inhibition at 0.018 mM
Ibuprofen
-
isozyme 1, 50% inhibition at 0.09 mM, isozyme 2, 50% inhibition at 0.008 mM
indomethacin
-
inhibition of prostaglandin G1 synthesis
indomethacin
-
-
indomethacin
-
-
indomethacin
-
-
indomethacin
-
acts on isozyme 1 and 2, 85% inhibition at 100 nM
indomethacin
-
reversible and time-dependent inhibition
indomethacin
-
50% inhibition at 100 nM
indomethacin
-
isozyme 1, 50% inhibition at 0.0017 mM, isozyme 2, 50% inhibition at 0.025 mM
indomethacin
-
inhibition in gastrointestinal tissues
indomethacin
-
isozyme 1 50% inhibition at 0.0005 mM, isozyme 2, 50% inhibition at 0.0003 mM
indomethacin
-
isozyme 1, 50% inhibition at 0.005 mM, isozyme 2, 50% inhibition at 0.130-0.160 mM
indomethacin
-
-
indomethacin
-
;
Ketoprofen
-
isozyme 1, 50% inhibition at 0.0005 mM, isozyme 2, 50% inhibition at 0.0025 mM
Ketoprofen
-
isozyme 1, 50% inhibition at 0.011 mM, isozyme 2, 50% inhibition at 0.018 mM
L-745
-
isozyme 1, 50% inhibition at 0.369 mM, isozyme 2, 50% inhibition at 0.002 mM
-
linoleic acid
-
;
Meclofenamic acid
-
-
Meclofenamic acid
-
isozyme 1, 50% inhibition at 0.002 mM, isozyme 2, 50% inhibition at 0.015 mM
Mefenamic acid
-
isozyme 1, 50% inhibition at 0.01 mM, isozyme 2, 50% inhibition at 0.0003 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
-
NS-398, selective for isozyme 2
N-[2-cyclohexyloxy-4-nitrophenyl]methanesulfonamide
-
50% inhibition at 81 nM
N-[2-cyclohexyloxy-4-nitrophenyl]methanesulfonamide
-
isozyme 1, 50% inhibition at 0.075 mM, isozyme 2, 50% inhibition at 0.002 mM
N-[2-cyclohexyloxy-4-nitrophenyl]methanesulfonamide
-
little inhibition in gastrointestinal tissues
N-[2-cyclohexyloxy-4-nitrophenyl]methanesulfonamide
-
isozyme 1, 50% inhibition at 0.017 mM, isozyme 2, 50% inhibition at 0.0001 mM
Naproxen
-
recombinant protein, 50% inhibition at 0.05-0.06 mM
Naproxen
-
isozyme 1, 50% inhibition at 0.0006 mM, isozyme 2, 50% inhibition at 0.002 mM
Naproxen
P05979, P79208
inhibitor of cyclooxigenase reaction; inhibitor of cyclooxigenase reaction
Naproxen
-
;
niflumic acid
-
isozyme 1, 50% inhibition at 0.016 mM, isozyme 2, 50% inhibition at 0.0001 mM
nimesulide
-
isozyme 1, 50% inhibition at 0.07 mM, isozyme 2, 50% inhibition at 0.0013 mM
nimesulide
-
isozyme 1, 50% inhibition at 0.009 mM, isozyme 2, 50% inhibition at 0.0005 mM
nimesulide
-
-
nimesulide
-
inhibits the cyclooxygenase activity, a COX-2-specific inhibitor
Non-steroidal anti-inflammatory agents
-
inhibition of cyclooxygenase activity
-
Non-steroidal anti-inflammatory agents
-
inhibition of cyclooxygenase activity
-
NS-398
-
;
NS-398
-
inhibits PTGS2
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
-
isozyme 1, 50% inhibition at 0.009-0.024 mM, isozyme 2, 50% inhibition at 0.070-0.240 mM
piroxicam
-
isozyme 1, 50% inhibition at 0.075 mM, isozyme 2, 50% inhibition at 0.002 mM
Propionic acid
-
-
quercetin 3-O-glucoside
-
;
SB203580
-
inhibitor of p38, reduces the PGHS-2 response to oxygen and glucose depivation by approximately 50%
SC-560
-
a standard PHS-1 inhibitor
SC-560
-
a PHS-1-specific inhibitor
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
-
-
meloxicam
-
isozyme 1, 50% inhibition at 0.005 mM, isozyme 2, 50% inhibition at 0.0004 mM
additional information
-
effect of cofactor, enzyme and substrate concentration on inhibition by human serum, haptoglobin and albumin
-
additional information
-
mechanism of selective inhibition
-
additional information
P79208
nimesulide inhibits PGHS-2 turnover in most brain regions
-
additional information
-
guava leaf extract inhibits the catalytic activity of the PGHS-1 isoform using linoleic acid as substrate (IC50 value of 0.055 mg of dry leaf extract); guava leaf extract inhibits the catalytic activity of the PGHS-2 isoform using linoleic acid as substrate (IC50 value of 0.56 mg of dry leaf extract); isozyme PGHS-1 is hardly inhibited by ellagic acid; isozyme PGHS-2 is hardly inhibited by ellagic acid
-
additional information
-
guava leaf extract inhibits the catalytic activity of the PGHS-1 and PGHS-2 isoforms using linoleic acid as substrate; guava leaf extract inhibits the catalytic activity of the PGHS-1 and PGHS-2 isoforms using linoleic acid as substrate; isozyme PGHS-1 is hardly inhibited by ellagic acid; isozyme PGHS-2 is hardly inhibited by ellagic acid
-
additional information
I6VVK9
algal PGHS is not inhibited by non-steroidal anti-inflammatory drugs that inhibit the mammalian enzymes
-
additional information
P23219, P35354
no inhibition of PGHS-2 oxygenase activity by 9-nitro-, 12-nitro-, 14-nitro, and 15-nitroarachidonic acid and by nitrooleic acid and nitrolinoleic acid; other nitro fatty acids tested, such as nitrooleic acid and nitrolinoleic acid, are unable to inhibit the enzyme activity
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5-hydroxytryptamine
-
stimulates
arachidonate
-
-
arachidonic acid
-
exogenous, increases hPHS activity
benzoquinone
-
stimulates conversion of prostaglandin G1 to H1
cysteine
-
stimulates
dopamine
-
3,4-dihydroxyphenylethylamine, stimulates
dopamine
-
-
Ellagic acid
-
at high concentration and in presence of cofactors inhibition, at low concentrations stimulation
epinephrine
-
stimulates conversion of prostaglandin G1 to H1
epinephrine
-
-
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
-
stimulates conversion of prostaglandin G1 to H1
hydroquinone
-
-
indole
-
stimulates conversion of prostaglandin G1 to H1
kynurenine
-
stimulates conversion of prostaglandin G1 to H1
Melatonin
-
stimulates
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
-
stimulates conversion of prostaglandin G1 to H1
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
-
stimulation of enzyme in crude extract by some amines
-
additional information
-
cyclooxygenase catalysis by prostaglandin H synthase-1 and -2 requires activation of the normally latent enzyme by peroxide-dependent generation of a free radical at Tyr385 (PGHS-1 numbering) in the cyclooxygenase active site. The Tyr385 radical has also been linked to self-inactivation processes that impose an ultimate limit on cyclooxygenase catalysis
-
additional information
-
USF proteins are involved in the trans-activation of the PGH-2 promoter in granulosa cells
-
additional information
-
hypoxia and glucose-free medium treatment synergistically increase PGHS-2 mRNA approximately 8fold; oxygen and glucose depivation induce PGHS-2 gene expression synergistically in neurons
-
additional information
O62698
the enzyme is induced by arachidonic acid up to 7.5-fold within 6 h, it is also induced by protein kinase C activators 4beta-PMA and PGF2alpha, all activation effects are blocked by PKC inhibitors, regulation, overview, protein kinase C induces PTGS2 independently of PPARs, i.e. peroxisome-proliferator-activated receptors
-
additional information
-
aqueous extracts of Chromoleana odorata, commonly used in traditional medicine as antiinflammatory drug against pains or as cataplasm to stop hemorrhage in Ivory Coast, the essential oil extracted from the fresh leaves activates the cyclooxygenase activity of the PGHS, overview
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0368
(4Z,7Z,10Z,13Z,16Z,19Z)-Docosahexaenoic acid
Q05769
pH 8.0, 25C, COX-2 mutant N580A
0.00945
(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoic acid
Q05769
pH 8.0, 25C, COX-2 mutant N580A
0.0031
alpha-linolenic acid
P23219, P35354
-
0.0048
alpha-linolenic acid
-
-
0.0101
alpha-linolenic acid
Q9PTN3, Q9PW89
-
0.082
alpha-linolenic acid
Q9PTN3, Q9PW89
-
0.0009
arachidonate
-
purified isoform PGHS-2, method: coupled, homo-vanilic acid
0.0011
arachidonate
-
purified isoform PGHS-2, method: direct, O2
0.0017
arachidonate
-
purified isoform PGHS-2, method: direct, O2
0.0019
arachidonate
-
purified isoform PGHS-1, method: direct, O2
0.002
arachidonate
-
purified isoform PGHS-2, method: direct, O2
0.0021
arachidonate
-
native enzyme
0.0021
arachidonate
-
pH 7.2, 30C, mutant enzyme N382L; pH 7.2, 30C, PGHS-2 wild-type enzyme
0.0022
arachidonate
-
pH 7.2, 30C, mutant enzyme N383D
0.0027
arachidonate
-
purified isoform PGHS-1, method: coupled, homo-vanilic acid
0.0029
arachidonate
-
pH 7.2, 30C, mutant enzyme N382D
0.00295
arachidonate
Q05769
pH 8.0, 25C, COX-2 mutant L531P
0.003
arachidonate
-
purified isoform PGHS-1, method: direct, O2
0.0032
arachidonate
-
mutant enzyme Y148F
0.0036
arachidonate
-
mutant enzyme Y404F
0.00365
arachidonate
Q05769
pH 8.0, 25C, COX-2 mutant L531A
0.0037
arachidonate
-
pH 7.2, 30C, mutant enzyme N383H
0.0037
arachidonate
-
purified isoform PGHS-1, method: direct, O2
0.0038
arachidonate
-
mutant enzyme Y348F
0.0041
arachidonate
-
pH 7.2, 30C, mutant enzyme N382A
0.0042
arachidonate
-
mutant enzyme Y504F
0.0043
arachidonate
-
mutant enzyme Y148F/Y348F/Y404F/Y504F
0.0045
arachidonate
-
purified isoform PGHS-1, method: direct, O2
0.005
arachidonate
-
purified isoform PGHS-2, method: direct, O2
0.0051
arachidonate
-
purified isoform PGHS-2, method: direct, O2
0.00514
arachidonate
Q05769
pH 8.0, 25C, COX-2 wild-type COX-2 and mutant N580A
0.009
arachidonate
-
purified isoform PGHS-2, method: direct, O2
0.0092
arachidonate
-
purified isoform PGHS-2, method: direct, O2
0.01
arachidonate
-
purified isoform PGHS-2, method: direct, arachidonate; purified isoform PGHS-2, method: direct, trimethyl phosphine oxide
0.0102
arachidonate
-
purified isoform PGHS-1, method: direct, arachidonate
0.011
arachidonate
-
purified isoform PGHS-1, method: coupled, homo-vanilic acid
0.015
arachidonate
-
purified isoform PGHS-1, method: direct, O2
0.001
arachidonic acid
-
isozyme 1 and 2
0.0021
arachidonic acid
-
wild-type, cyclooxygenase activity
0.0034
arachidonic acid
-
mutant Y348F/Y504F, cyclooxygenase activity
0.0038
arachidonic acid
-
mutant Y348F, cyclooxygenase activity
0.0042
arachidonic acid
-
mutant Y504F, cyclooxygenase activity
0.0045
arachidonic acid
-
isozyme 1
0.005
arachidonic acid
-
isozyme 2
0.006
arachidonic acid
-
-
0.0083
arachidonic acid
-
-
0.015
arachidonic acid
-
-
0.16
arachidonic acid
-
-
0.0052
cis-11,14-eicosadienoic acid
P23219, P35354
-
0.0091
cis-11,14-eicosadienoic acid
-
-
0.0011
cis-4,7,10,13,16,19-docosahexaenoic acid
P23219, P35354
-
0.0033
cis-4,7,10,13,16,19-docosahexaenoic acid
-
-
0.0318
cis-4,7,10,13,16,19-docosahexaenoic acid
Q9PTN3, Q9PW89
-
0.07
cis-4,7,10,13,16,19-docosahexaenoic acid
Q9PTN3, Q9PW89
-
0.0012
cis-5,8,11,14,17-eicosapentaenoic acid
P23219, P35354
-
0.0031
cis-5,8,11,14,17-eicosapentaenoic acid
-
-
0.0153
cis-5,8,11,14,17-eicosapentaenoic acid
Q9PTN3, Q9PW89
-
0.039
cis-5,8,11,14,17-eicosapentaenoic acid
Q9PTN3, Q9PW89
-
0.0017
cis-5,8,11,14-eicosatetraenoic acid
P23219, P35354
-
0.0024
cis-5,8,11,14-eicosatetraenoic acid
Q9PTN3, Q9PW89
-
0.003
cis-5,8,11,14-eicosatetraenoic acid
-
-
0.013
cis-5,8,11,14-eicosatetraenoic acid
Q9PTN3, Q9PW89
-
0.0027
cis-7,10,13,16-docosatetraenoic acid
P23219, P35354
-
0.007
cis-7,10,13,16-docosatetraenoic acid
-
-
0.0357
cis-7,10,13,16-docosatetraenoic acid
Q9PTN3, Q9PW89
-
0.061
cis-7,10,13,16-docosatetraenoic acid
Q9PTN3, Q9PW89
-
0.002
cis-8,11,14-eicosatrienoic acid
P23219, P35354
-
0.0055
cis-8,11,14-eicosatrienoic acid
-
-
0.0059
cis-8,11,14-eicosatrienoic acid
Q9PTN3, Q9PW89
-
0.036
cis-8,11,14-eicosatrienoic acid
Q9PTN3, Q9PW89
-
0.0048
gamma-linolenic acid
P23219, P35354
-
0.0071
gamma-linolenic acid
-
-
0.162
gamma-linolenic acid
Q9PTN3, Q9PW89
-
0.08
guaiacol
-
pH 8.0, 23C, wild-type enzyme
0.29
guaiacol
-
pH 8.0, 23C, mutant enzyme N382L
1.3
H2O2
-
pH 8.0, 23C, wild-type enzyme
5.5
H2O2
-
pH 8.0, 23C, mutant enzyme N382L
0.0055
linoleic acid
-
isozyme PGHS-1, in 100 mM Tris-HCl buffer (pH 7.4), at 24C
0.0083
N,N,N',N'-tetramethyl-p-phenylenediamine
-
pH 7.2, 30C, mutant enzyme N383H
0.01
N,N,N',N'-tetramethyl-p-phenylenediamine
-
pH 7.2, 30C, mutant enzyme N383D
0.0156
N,N,N',N'-tetramethyl-p-phenylenediamine
-
pH 7.2, 30C, mutant enzyme N382D
0.0163
N,N,N',N'-tetramethyl-p-phenylenediamine
-
pH 7.2, 30C, PGHS-2 wild-type enzyme
0.0854
N,N,N',N'-tetramethyl-p-phenylenediamine
-
pH 7.2, 30C, mutant enzyme N382L
0.005
O2
-
purified isoform PGHS-1, method: direct, O2
0.0055
O2
-
purified isoform PGHS-1, method: direct, O2
0.01
O2
-
purified isoform PGHS-1, method: direct, arachidonate
0.011
O2
-
purified isoform PGHS-1, method: direct, O2
0.02
trans-5-phenyl-4-pentenyl-1-hydroperoxide
-
mutant enzyme Y148F
0.061
trans-5-phenyl-4-pentenyl-1-hydroperoxide
-
mutant enzyme Y404F
0.072
trans-5-phenyl-4-pentenyl-1-hydroperoxide
-
mutant enzyme Y348F
0.103
trans-5-phenyl-4-pentenyl-1-hydroperoxide
-
mutant enzyme Y148F/Y348F/Y385F/Y404F/Y504F
0.138
trans-5-phenyl-4-pentenyl-1-hydroperoxide
-
native enzyme
0.339
trans-5-phenyl-4-pentenyl-1-hydroperoxide
-
mutant enzyme Y385F
0.37
trans-5-phenyl-4-pentenyl-1-hydroperoxide
-
mutant enzyme Y148F/Y348F/Y404F/Y504F
0.437
trans-5-phenyl-4-pentenyl-1-hydroperoxide
-
mutant enzyme Y504F
0.0068
linoleic acid
-
isozyme PGHS-2, in 100 mM Tris-HCl buffer (pH 7.4), at 24C
additional information
additional information
-
the cyclooxygenase reaction shows Michaelis-Menten kinetics over a wide range of oxygen concentrations in the absence of electron donor. Kinetics analysis, overview
-
additional information
additional information
Q05769
Michaelis-Menten kinetics, overview
-
additional information
additional information
I6VVK9
Michaelis-Menten kinetics
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3.45
(4Z,7Z,10Z,13Z,16Z,19Z)-Docosahexaenoic acid
Q05769
pH 8.0, 25C, COX-2 mutant N580A
8.7
(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoic acid
Q05769
pH 8.0, 25C, COX-2 mutant N580A
27
arachidonate
Q05769
pH 8.0, 25C, COX-2 mutant N580A
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
9
(4Z,7Z,10Z,13Z,16Z,19Z)-Docosahexaenoic acid
Q05769
pH 8.0, 25C, COX-2 mutant N580A
40206
920
(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoic acid
Q05769
pH 8.0, 25C, COX-2 mutant N580A
41642
5240
arachidonate
Q05769
pH 8.0, 25C, COX-2 mutant N580A
619
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00027
nimesulide
-
mutant Y348F/Y504F, cyclooxygenase inhibition
0.0009
nimesulide
-
mutant Y504F, cyclooxygenase inhibition
0.001
nimesulide
-
wild-type, cyclooxygenase inhibition
0.005
indomethacin
-
-
additional information
additional information
P23219, P35354
inhibition kinetics of the isozymes' peroxidase activity, overview
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.003
alpha-linolenic acid
-
inhibition of PGHS-2
0.0212
alpha-linolenic acid
-
inhibition of PGHS-1
0.0008
indomethacin
-
inhibition of PGHS-2
0.0009
indomethacin
-
inhibition of PGHS-1
0.0026
linoleic acid
-
inhibition of PGHS-2
0.0198
linoleic acid
-
inhibition of PGHS-1
0.0026
NS-398
-
inhibition of PGHS-2
0.0507
NS-398
-
inhibition of PGHS-1
0.1226
oleic acid
-
inhibition of PGHS-2
0.1245
oleic acid
-
inhibition of PGHS-1
0.0186
peroxynitrite
-
cyclooxygenase activity, peroxynitrite is incubated with the resting enzyme and 30 s later, activity and protein nitration is analyzed
0.0222
peroxynitrite
-
peroxidase activity, peroxynitrite is incubated with the resting enzyme and 30 s later, activity and protein nitration is analyzed
0.03
peroxynitrite
-
cyclooxygenase activity, enzyme is incubated with peroxynitrite in the presence of peroxides and arachidonic acid
0.0388
peroxynitrite
-
peroxidase activity, enzyme is incubated with peroxynitrite in the presence of peroxides and arachidonic acid
0.018
quercetin
-
isozyme PGHS-1, in 100 mM Tris-HCl buffer (pH 7.4), at 24C
0.086
quercetin
-
isozyme PGHS-2, in 100 mM Tris-HCl buffer (pH 7.4), at 24C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
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
Q9PTN3, Q9PW89
cyclooxygenase activity for partially purified prostaglandin H synthase 1 of Salvelinus fontinalis, tPGHS-1
4220
-
purified recombinant His6-tagged PGHS-2, pH 8.0, 37C
15000
Q9PTN3, Q9PW89
cyclooxygenase activity for partially purified prostaglandin H synthase 2 of Salvelinus fontinalis, tPGHS-2
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 7.3
-
formation of prostaglandin E2 from arachidonic acid
7.2
P23219, P35354
cyclooxygenase activity assay; cyclooxygenase activity assay
7.2
-
cyclooxygenase activity assay
7.2
Q9PTN3, Q9PW89
cyclooxygenase activity assay; cyclooxygenase activity assay
7.4
-
activity assay, determination of cyclooxygenase and peroxidase activity
7.4
-
assay at
7.4
P23219, P35354
prostaglandin endoperoxide H synthase assay at; prostaglandin endoperoxide H synthase assay at
7.5 - 8
-
formation of prostaglandin F2alpha
7.8
-
enzyme-linked immunoassay for PGE2
8 - 8.5
-
formation of prostaglandin E2 and D2
8
-
synthesis of prostaglandin G1, conversion to prostaglandin H1
8
-
cyclooxygenase activity assay
8
-
lipoxygenase activity assay
8
P05979, P79208
kinetic assay; kinetic assay
8
P23219, P35354
lipoxygenase activity assay; lipoxygenase activity assay
8
Q9PTN3, Q9PW89
lipoxygenase activity assay; lipoxygenase activity assay
8
-
activity assay
8
-
activity assay; activity assay
8
-
assay at
8
Q05769
assay at
8
I6VVK9
cyclooxygenase activity assay at
8
-
assay at
8.1
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
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
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22
-
lipoxygenase activity assay at room temperature
22
-
activity assay at room temperature; activity assay at room temperature
23
P23219, P35354
room temperature, 22-23C, lipoxygenase activity assay; room temperature, 22-23C, lipoxygenase activity assay
23
Q9PTN3, Q9PW89
room temperature, 22-23C, lipoxygenase activity assay; room temperature, 22-23C, lipoxygenase activity assay
25
P05979, P79208
kinetic assay; kinetic assay
25
P23219, P35354
cyclooxygenase activity assay using a standard electrode; cyclooxygenase activity assay using a standard electrode
25
-
cyclooxygenase activity assay using a standard electrode
25
Q9PTN3, Q9PW89
cyclooxygenase activity assay using a standard electrode; cyclooxygenase activity assay using a standard electrode
25
-
activity assay, determination of cyclooxygenase and peroxidase activity
25
-
activity assay
25
-
assay at
25
Q05769
assay at
25
I6VVK9
cyclooxygenase activity assay at
30
-
cyclooxygenase activity assay
30
P23219, P35354
cyclooxygenase activity assay using a high sensitivity electrode; cyclooxygenase activity assay using a high sensitivity electrode
30
-
cyclooxygenase activity assay using a high sensitivity electrode
30
Q9PTN3, Q9PW89
cyclooxygenase activity assay using a high sensitivity electrode; cyclooxygenase activity assay using a high sensitivity electrode
37
-
assay at
37
-
assay at
37
P23219, P35354
prostaglandin endoperoxide H synthase assay at; prostaglandin endoperoxide H synthase assay at
37
-
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5 - 30
P23219, P35354
;
5 - 30
-
-
5 - 30
Q9PTN3, Q9PW89
;
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
fetal brain
Manually annotated by BRENDA team
-
PGHS-2 has lowest abundance in brain stem and pituitary gland, PGSHS-1 has lowest abundance in brain stem and pituitary gland
Manually annotated by BRENDA team
-
PGHS-2 has highest abundance in hippocampus and cerebral cortex, PGSHS-1 has highest abundance in hippocampus and cerebral cortex
Manually annotated by BRENDA team
-
seminal plasma induces and potentiates the expression of PTGS2 in cervicovaginal cells and tissues
Manually annotated by BRENDA team
-
significant increase in mRNA for PGHS-2 after treatment with prostaglandin F2alpha. PGHS-1 mRNA content remains unchanged
Manually annotated by BRENDA team
O62664
PTGS1 enzyme activity is higher in late corpora lutea and lower in regressive ones, PTGS2 increases from early to late corpora lutea and lowers in regressive ones
Manually annotated by BRENDA team
O62698
endometrial stromal cells
Manually annotated by BRENDA team
-
caput and cauda
Manually annotated by BRENDA team
O62698
stroma
Manually annotated by BRENDA team
-
periovulatory granulosa cell
Manually annotated by BRENDA team
-
PGHS-2 has highest abundance in hippocampus and cerebral cortex, PGSHS-1 has highest abundance in hippocampus and cerebral cortex
Manually annotated by BRENDA team
O62664
PTGS2, during early, mid, and late stages
Manually annotated by BRENDA team
-
increased expression of PTGS2
Manually annotated by BRENDA team
-
ovarian surface epithelium
Manually annotated by BRENDA team
-
PGHS-2 has lowest abundance in brain stem and pituitary gland, PGSHS-1 has lowest abundance in brain stem and pituitary gland
Manually annotated by BRENDA team
-
human neuroblastoma cell
Manually annotated by BRENDA team
-
somatic and spermatogenic cells
Manually annotated by BRENDA team
O62698
in the stroma of endometrial epithelium
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
-
enzyme can be associated with endoplasmic reticulum, nuclear envelope and plasma membrane even within the same cell
Manually annotated by BRENDA team
additional information
-
enzyme can be associated with endoplasmic reticulum, nuclear envelope and plasma membrane even within the same cell
Manually annotated by BRENDA team
additional information
-
distribution of isozymes 1,2 in gastrointestinal tissues
Manually annotated by BRENDA team
additional information
-
distribution in different organs
Manually annotated by BRENDA team
additional information
-
relationship of PGHS-2 and PGHS-1 mRNA and activity in brain tissues, overview
Manually annotated by BRENDA team
additional information
-
quantitative real-time RT-PCR enzyme expression analysis, overview
Manually annotated by BRENDA team
additional information
-
quantitative RT-PCR enzyme expression and immunohistochemic analysis, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
immunoreactive PGHS-2 is localized to the cytoplasm of amnion epithelial cells, amnion-chorion mesenchymal cells, and chorion trophoblast cells and in scattered stromal cells
Manually annotated by BRENDA team
-
probably associated with
-
Manually annotated by BRENDA team
Q05769
associated
Manually annotated by BRENDA team
-
membrane associated glycoprotein
Manually annotated by BRENDA team
additional information
-
enzyme can be associated with endoplasmic reticulum, nuclear envelope and plasma membrane even within the same cell
-
Manually annotated by BRENDA team
additional information
-
enzyme can be associated with endoplasmic reticulum, nuclear envelope and plasma membrane even within the same cell
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
65000
-
immunoblot
673515
65620
-
amino acid sequence deduced from nucleotide sequence of cDNA, MW of unglycosylated enzyme
438369
68000
-
human cyclooxygenase-1, estimated by SDS-PAGE and Western blotting, detected with a cyclooxygenase-1 antibody
673459
70000
-
confirmed by SDS-PAGE, Western blot analysis and MALDI-TOF
675273
72000
P05979, P79208
monomer; monomer
672300
72000
-
estimated by PAGE and Western blotting
672839
72000
-
human cyclooxygenase-1bdeltaG, estimated by SDS-PAGE and Western blotting, detected with a cyclooxygenase-1 and a FLAG-tag antibody
673459
72000
-
isozyme PTGS-2
701168
73000
-
determined by SDS-PAGE and immunoblotting
672161
300000 - 350000
-
gel filtration
438375
330000
I6VVK9
about, recombinant His-tagged enzyme, gel filtration
727083
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 72000, SDS-PAGE
?
-
x * 68000, SDS-PAGE
?
-
x * 72000, SDS-PAGE, oxygenase and peroxidase activity are present in a single polypeptide chain, in nonionic detergent the enzyme is a dimer of 2 identical subunits
?
-
x * 75000, SDS-PAGE, isozyme 1 and 2
?
-
x * 70000, SDS-PAGE in absence and presence of 2-mercaptoethanol
homodimer
-
-
homodimer
Q05769
-
homodimer
P23219, P35354
PGHS-1 is a homodimer of 70 kDa whose dimerization is required for structural integrity and catalytic activity
tetramer
I6VVK9
4 * 63500, recombinant His-tagged enzyme, SDS-PAGE
homodimer
P23219, P35354
PGHS-2 is a homodimer of 70 kDa whose dimerization is required for structural integrity and catalytic activity
additional information
I6VVK9
structure comparisons, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
-
both isozyme 1 and 2
glycoprotein
-
membrane associated glycoprotein
glycoprotein
Q05769
-
glycoprotein
-
-
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, 23C, 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
Q05769
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
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 8
-
24C, 5 min, stable
438375
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
-
pH 8.0, 5 min, stable
438374
50
-
pH 8.0, 5 min, complete loss of activity
438375
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
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 4C
-
diethyldithiocarbamate stabilizes
-
ethylene glycol stabilizes
-
flufenamate stabilizes
-
glycerol stabilizes
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4C, Opuntia imbricata-immobilized enzyme, 2 days, 90-95% loss of initial activity
-
4C, Opuntia imbricata-immobilized enzyme, 24 h, 36-48% of initial activity is maintained after storage
-
4C, Opuntia imbricata-immobilized enzyme, 4 days, complete loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged enzyme 138fold from Escherichia coli strain BL21(DE3)RP membranes by nickel affinity chromatography, and anion exchange chromatography
I6VVK9
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 protein expressed in Sf9 cells; recombinant protein expressed in Sf9 cells
P23219, P35354
using nickel affinity chromatography
-
recombinant His-tagged wild-type and mutant COX-2 proteins by nickel affinity chromatography and gel filtration
Q05769
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
-
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
-
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
Q9PTN3, Q9PW89
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
codes for protein of 604 amino acids, 89% identity to human protein
-
PGHS DNA and amiino acid sequence determination and analysis, sequence comparisons
I6VCP8
PGHS DNA and amino acid sequence determination and analysis, sequence comparisons, functional expression of His-tagged enzyme in Escherichia coli strain BL21(DE3)RP
I6VVK9
;
P23219, P35354
all mutants are overexpressed in the baculovirus system as detergent-soluble full-length proteins
-
expressed in colon carcinoma cells COLO320DM; expressed in colon carcinoma cells COLO320DM
-
expressed in COS-1 cells; into the mammalian expression vector pcDNA3
-
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
-
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
-
expression of His-tagged wild-type and mutant COX-2 proteins
Q05769
COX-1b, expression in COS-7 cells
-
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
Q9PTN3, Q9PW89
isozymes 1 and 2
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
when NCI-H292 cells are transfected with E2F1 siRNA, PTGS2 expression is attenuated
-
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
-
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
-
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)
-
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
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
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
-
mutant
Y348F
-
mutant enzyme has specific cyclooxygenase activity approximately half that of native enzyme
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
Y504F
-
mutant
Y504F
-
mutant enzyme has cyclooxygenase activity comparable to that of the native enzyme
Y76C
-
mutant, relative activity: 70%
L531A
Q05769
site-directed mutagenesis, the mutant shows reduced Vmax and Km with arachidonate compared to the wild-type COX-2
L531F
Q05769
site-directed mutagenesis, the mutant shows reduced Vmax and Km with arachidonate compared to the wild-type COX-2
L531P
Q05769
site-directed mutagenesis, the mutant shows reduced Vmax and Km with arachidonate compared to the wild-type COX-2
L531T
Q05769
site-directed mutagenesis, the mutant shows reduced Vmax and Km with arachidonate compared to the wild-type COX-2
N580A
Q05769
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
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
Q05769
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
use of peroxidase activity for luminol assay of inflammation
medicine
-
study of aspirin acetylated enzyme in order to inhibit prostaglandin synthesis
medicine
-
inhibition of cyclooxygenases is a mode of antiinflammatory drugs
medicine
-
inhibition of prostaglandin synthesis by suppression of enzyme expression using isomallotochromanol
medicine
-
amphetamines, bioactivated by prostaglandin H synthase, cause reactive oxygen species formation, implicated in amphetamine-initiated neurodegeneration
medicine
-
clinical important drug target