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Literature summary for 1.14.99.1 extracted from

  • Trostchansky, A.; Bonilla, L.; Thomas, C.P.; ODonnell, V.B.; Marnett, L.J.; Radi, R.; Rubbo, H.
    Nitroarachidonic acid, a novel peroxidase inhibitor of prostaglandin endoperoxide H synthases 1 and 2 (2011), J. Biol. Chem., 286, 12891-12900.
    View publication on PubMedView publication on EuropePMC

Inhibitors

Inhibitors Comment Organism Structure
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 Homo sapiens
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 Homo sapiens
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 Homo sapiens
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 Homo sapiens
additional information 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 Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Iron 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 Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
arachidonate + AH2 + 2 O2 Homo sapiens
-
prostaglandin H2 + A + H2O
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P23219 isozyme PGHS-1
-
Homo sapiens P35354 isozyme PGHS-2
-

Source Tissue

Source Tissue Comment Organism Textmining
blood platelet
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
arachidonate + AH2 + 2 O2
-
Homo sapiens prostaglandin H2 + A + H2O
-
?
arachidonate + reduced N,N,N',N'-tetramethylphenylenediamine + 2 O2
-
Homo sapiens prostaglandin H2 + oxidized N,N,N',N'-tetramethylphenylenediamine + H2O
-
?
additional information PGHS-1 also exhibits peroxidase activity Homo sapiens ?
-
?
additional information PGHS-2 also exhibits peroxidase activity Homo sapiens ?
-
?

Subunits

Subunits Comment Organism
homodimer PGHS-1 is a homodimer of 70 kDa whose dimerization is required for structural integrity and catalytic activity Homo sapiens
homodimer PGHS-2 is a homodimer of 70 kDa whose dimerization is required for structural integrity and catalytic activity Homo sapiens

Synonyms

Synonyms Comment Organism
COX
-
Homo sapiens
PGHS
-
Homo sapiens
prostaglandin endoperoxide H synthase
-
Homo sapiens
prostaglandin endoperoxide H synthase 1
-
Homo sapiens
prostaglandin endoperoxide H synthase 2
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
prostaglandin endoperoxide H synthase assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
prostaglandin endoperoxide H synthase assay at Homo sapiens

Cofactor

Cofactor Comment Organism Structure
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 Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
additional information
-
additional information inhibition kinetics of the isozymes' peroxidase activity, overview Homo sapiens

General Information

General Information Comment Organism
malfunction PGHS-1 inhibition in activated human plateletts significantly decreases PGHS-1-dependent thromboxane B2 formation in parallel with a decrease in platelet aggregation Homo sapiens