Information on EC 5.3.99.5 - Thromboxane-A synthase

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The expected taxonomic range for this enzyme is: Eukaryota

EC NUMBER
COMMENTARY
5.3.99.5
-
RECOMMENDED NAME
GeneOntology No.
Thromboxane-A synthase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate = (5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
-
-
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate = (5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
role of the thiolate ligand in the oxygen activation mechanism
-
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate = (5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
mechanism
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
intramolecular oxidoreduction
-
-
-
-
isomerization
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
Arachidonic acid metabolism
-
C20 prostanoid biosynthesis
-
Metabolic pathways
-
SYSTEMATIC NAME
IUBMB Comments
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate isomerase
Converts prostaglandin H2 into thromboxane A2. A heme-thiolate protein.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Synthetase, thromboxane
-
-
-
-
Thromboxan synthetase
-
-
-
-
thromboxane A synthase 1
-
-
thromboxane A-synthase
-
-
thromboxane A2 synthase
-
-
thromboxane A2 synthase
-
-
thromboxane A2 synthase 1
-
-
Thromboxane A2 synthetase
-
-
-
-
thromboxane synthase
-
-
thromboxane synthase
-
-
Thromboxane synthetase
-
-
-
-
TXA synthase
-
-
-
-
TxA-synthase
-
-
TXA2 synthase
-
-
TXA2 synthase
-
-
TXAS
-
-
-
-
TXS
-
-
-
-
TxSI
-
-
CAS REGISTRY NUMBER
COMMENTARY
61276-89-9
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
patients with colorectal carcinoma
-
-
Manually annotated by BRENDA team
recombinant enzyme
-
-
Manually annotated by BRENDA team
resonance raman spectrum of recombinant TXAS
-
-
Manually annotated by BRENDA team
unrelated families of Tunasian and Pakistani origin with Ghosal hematodiaphyseal dysplasia syndrome (GHDD, i.e. Ghosal syndrome), a rare autosomal recessive disorder characterized by increased bone densitiy
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
inhibition of thromboxane synthase induces lung cancer cell death via increasing the nuclear p27
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
12-L-hydroxy-5,8,10-heptadecaotrienoic acid + malondialdehyde
show the reaction diagram
-
-
ratio of TXA2/heptadecatrienoic acid/malondialdehyde, 1/1/1
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
12-L-hydroxy-5,8,10-heptadecaotrienoic acid + malondialdehyde
show the reaction diagram
-
-
ratio of TXA2/heptadecatrienoic acid/malondialdehyde, 1/1/1
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9a,11a-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
15-hydroperoxyeicosatetraenoic acid
13-hydroxy-14,15-epoxy-5,8,11-eicosatrienoic acid + 15-ketoeicosatetraenoic acid + 13-hydroxy-14,15-epoxy-5,8,11-eicosatrienoic acid + 15-ketoeicosatetraenoic acid
show the reaction diagram
-
-
13-hydroxy-14,15-epoxy-5,8,11-eicosatrienoic acid and 15-ketoeicosatetraenoic acid result from homolytic cleavage of the O-O bond, whereas 13-hydroxy-14,15-epoxy-5,8,11-eicosatrienoic acid + 15-ketoeicosatetraenoic acid results from heterolytic cleavage. About 60% of substrate is cleaved homolytically, and maximal velocity of homolytic cleavage is about 1.4fold faster than heterolytic cleavage
-
?
15-Ketoprostaglandin H2
?
show the reaction diagram
-
-
-
-
-
prostaglandin E2
thromboxane A2 + ?
show the reaction diagram
-
-
thromoboxane A2 is non-enzymatically converted to thromboxane B2, which is secretion is measured to analyze the enzyme activity
-
?
Prostaglandin G2
15-Hydroperoxythromboxane B2 + 12-hydroperoxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGG2
-
-
-
Prostaglandin G2
15-Hydroperoxythromboxane B2 + 12-hydroperoxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGG2
-
-
Prostaglandin G2
15-Hydroperoxythromboxane B2 + 12-hydroperoxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGG2
-
-
Prostaglandin G2
12-Hydroperoxythromboxane A2 + 12-hydroperoxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGG2
the reaction products are transformed to thromboxane B2 and 12-hydroxy-5,8,10-heptadecatrienoic acid by SnCl2 reduction and to 12-keto-5,8,10-heptadecatrienoic acid and 15-ketothromboxane B2 by lead tetraacetate dehydration
-
prostaglandin H1
12(L)-hydroxy-8,10-heptadecadienoic acid + thromboxane B1
show the reaction diagram
-
-
-
-
prostaglandin H1
12(L)-hydroxy-8,10-heptadecadienoic acid + thromboxane B1
show the reaction diagram
-
-
-
-
-
prostaglandin H1
12(L)-hydroxy-8,10-heptadecadienoic acid + thromboxane B1
show the reaction diagram
-
-
thromboxane B2 is not mentioned as product
-
prostaglandin H1
12(L)-hydroxy-8,10-heptadecadienoic acid + thromboxane B1
show the reaction diagram
-
-
thromboxane B1 is scarcely detectable, the major product is 12(L)-hydroxy-8,10-heptadecadienoic acid
-
prostaglandin H1
12(L)-hydroxy-8,10-heptadecadienoic acid + thromboxane B1
show the reaction diagram
-
-
thromboxane B1 is scarcely detectable, the major product is 12(L)-hydroxy-8,10-heptadecadienoic acid
-
prostaglandin H1
12(L)-hydroxy-8,10-heptadecadienoic acid + thromboxane B1
show the reaction diagram
-
-
thromboxane B1 is scarcely detectable, the major product is 12(L)-hydroxy-8,10-heptadecadienoic acid
-
prostaglandin H1
12(L)-hydroxy-8,10-heptadecadienoic acid + thromboxane B1
show the reaction diagram
-
poor substrate
-
-
-
prostaglandin H1
12(L)-hydroxy-8,10-heptadecadienoic acid + thromboxane B1
show the reaction diagram
-
activity is equal to that with prostaglandin H2
thromboxane B1 is scarcely detectable, the major product is 12(L)-hydroxy-8,10-heptadecadienoic acid
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
-
-
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
-
-
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
-
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
-
-
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
-
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
-
-
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
-
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
-
-
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
-
-
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
-
-
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
-
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
-
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
-
-
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
-
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
-
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
-
-
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
-
-
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
the thromboxane A2 that is formed by the enzyme is transformed to thromboxane B2
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
the thromboxane A2 that is formed by the enzyme is transformed to thromboxane B2
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
+ malondialdehyde
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
+ malondialdehyde
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
the ratio of 12-hydroxy-5,8,10-heptadecatrienoic acid to thromboxane B2 varries from 1.6 to 2.1 depending on the reaction conditions
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
the ratio of thromboxane to C17 hydroxyfatty acid formation is 1:1
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
the ratio of thromboxane to C17 hydroxyfatty acid formation is 1:1
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
the ratio of thromboxane to C17 hydroxyfatty acid formation is 1:1
-
Prostaglandin H2
Thromboxane B2 + 12(L)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
i.e. PGH2
thromboxane A2 is an intermediate
-
prostaglandin H2
thromboxane A2 + ?
show the reaction diagram
-
-
-
-
?
prostaglandin H2
thromboxane A2 + ?
show the reaction diagram
-
-
-
-
?
prostaglandin H2
thromboxane B2 + 12(S)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
-
-
-
?
prostaglandin H2
thromboxane B2 + 12(S)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
-
-
-
?
prostaglandin H2
thromboxane B2 + 12(S)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
-
-
-
?
Prostaglandin H3
Thromboxane B3 + 12(L)-hydroxy-5,8,10,14-heptadecatetraenoic acid
show the reaction diagram
-
-
the ratio of thromboxane to C17 hydroxyfatty acid formation is 1:1. Thromboxane A2 is fully transformed to thromboxane B2
-
Prostaglandin H3
Thromboxane B3 + DELTA14-12-hydroperoxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
-
-
-
13(S)-Prostaglandin H2
10(S)-12-Hydroperoxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
-
-
-
15(S)-Hydroxy-11alpha,9alpha-epoxymethano-5(Z),13(E)-prostadienoic acid
additional information
-
-
in presence of iodosylbenzene
3 different hydroxylated derivatives of 15(S)-hydroxy-11alpha,9alpha-epoxymethano-5(Z),13(E)-prostadienoic acid
-
8-Isoprostaglandin H2
8-cis-12-Hydroperoxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
-
-
-
additional information
?
-
-
production of thromboxane A2, an unstable bioregulator that induces platelet release reaction, platelet aggregation and smooth muscle contraction
-
-
-
additional information
?
-
-
cyclooxygenase-2 and thromboxane synthase are involved in the diosgenin-induced megakaryocytic differentiation in HEL cells
for analysis of the thromboxane synthase activity the secretion of thromoxane B2 is measured. Thromboxane B2 is a nonenzymatic conversion product of thromobxane A1, the product of the thromboxane synthase activity
-
-
additional information
?
-
-
TXAS is one of the terminal enzymes of the arachidonic acid cascade and converts prostaglandins H2 into thromobane A2 in the endoplasmic reticulum
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
show the reaction diagram
-
-
i.e. TXA2
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
12-L-hydroxy-5,8,10-heptadecaotrienoic acid + malondialdehyde
show the reaction diagram
-
-
ratio of TXA2/heptadecatrienoic acid/malondialdehyde, 1/1/1
?
prostaglandin H2
thromboxane A2 + ?
show the reaction diagram
-
-
-
-
?
prostaglandin H2
thromboxane A2 + ?
show the reaction diagram
-
-
-
-
?
prostaglandin H2
thromboxane B2 + 12(S)-hydroxy-5,8,10-heptadecatrienoic acid
show the reaction diagram
-
-
-
-
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
12-L-hydroxy-5,8,10-heptadecaotrienoic acid + malondialdehyde
show the reaction diagram
-
-
ratio of TXA2/heptadecatrienoic acid/malondialdehyde, 1/1/1
?
additional information
?
-
-
production of thromboxane A2, an unstable bioregulator that induces platelet release reaction, platelet aggregation and smooth muscle contraction
-
-
-
additional information
?
-
-
cyclooxygenase-2 and thromboxane synthase are involved in the diosgenin-induced megakaryocytic differentiation in HEL cells
for analysis of the thromboxane synthase activity the secretion of thromoxane B2 is measured. Thromboxane B2 is a nonenzymatic conversion product of thromobxane A1, the product of the thromboxane synthase activity
-
-
additional information
?
-
-
TXAS is one of the terminal enzymes of the arachidonic acid cascade and converts prostaglandins H2 into thromobane A2 in the endoplasmic reticulum
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
cytochrome P450
-
-
-
cytochrome P450
-
a cytochrome P450 enzyme
-
cytochrome P450
-
-
-
heme
-
hemoprotein
heme
-
1 heme per polypeptide chain of MW 58800; the heme-thiolate group of the enzyme is required to split and activate the endoperoxide bond of prostaglandin H2
heme
-
comparison of thromboxane A2 synthase model based on the P450BM-3 with another thromboxane A2 synthase model based on the P450cam structure indicates that P450BM-3 is a more suitable template for homology modeling of thromboxane A2 synthase. P450BM-3 and p450cam are hemoprotein domains of cytochrome; hemoprotein
heme
-
contains one heme per 58000 MW protein. The major part of the enzyme is converted by the elution procedure to the inactive P420 form, a minor part is in its native heme-thiolate conformation; hemoprotein
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(+)-(E)-7-[4-[4-[[[2-(trans)-phenylcyclopropyl]amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid
-
0.0000085 mM, 50% inhibition
(+)-5-(2-imidazole-1-ethyloxy)-1-indan-carboxylic acid
-
trivial name camonagrel
(+/-)-6-(1-Imidazolylmethyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid hydrochloride hemihydrate
-
improvement of the renal function with the selective thromboxane A2 synthetase inhibitor
(-)-(E)-7-[4-[4-[[[2-(trans)-phenylcyclopropyl]amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid
-
0.0000059 mM, 50% inhibition
(5E)-6-(3-(2-cyano-3,3-dimethyl)guanidinophenyl)-6-(3-pyridyl)hex-5-enoic acid
-
0.000026 mM, 50% inhibition
(5E)-6-(3-(2-cyano-3-(1-adamantyl)-guanidino)phenyl)-6-(3-pyridyl)hex-5-enoic acid
-
0.000003 mM, 50% inhibition
(5E)-6-(3-(2-cyano-3-(2-dimethylaminoethyl)-guanidino)phenyl)-6-(3-pyridyl)hex-5-enoic acid
-
0.0029 mM, 50% inhibition
(5E)-6-(3-(2-cyano-3-(2-methylpropyl)guanidino)phenyl)-6-(3-pyridyl)hex-5-enoic acid
-
0.000025 mM, 50% inhibition
(5E)-6-(3-(2-cyano-3-(3-methylbutyl)guanidino)phenyl)-6-(3-pyridyl)hex-5-enoic acid
-
0.000003 mM, 50% inhibition
(5E)-6-(3-(2-cyano-3-(3-pyridylmethyl)-guanidino)phenyl)-6-(3-pyridyl)hex-5-enoic acid
-
0.000032 mM, 50% inhibition
(5E)-6-(3-(2-cyano-3-benzylguanidino)phenyl)-6-(3-pyridyl)hex-5-enoic acid
-
0.000011 mM, 50% inhibition
(5E)-6-(3-(2-cyano-3-cyclohexyl-guanidino)phenyl)-6-(3-pyridyl)hex-5-enoic acid
-
0.000003 mM, 50% inhibition
(5E)-6-(3-(2-cyano-3-cyclopentyl-guanidino)phenyl)-6-(3-pyridyl)hex-5-enoic acid
-
0.000003 mM, 50% inhibition
(5E)-6-(3-(2-cyano-3-cyclopropyl-guanidino)phenyl)-6-(3-pyridyl)hex-5-enoic acid
-
0.00038 mM, 50% inhibition
(5E)-6-(3-(2-cyano-3-isopropyl)guanidinophenyl)-6-(3-pyridyl)hex-5-enoic acid
-
0.000024 mM, 50% inhibition
(5E)-6-(3-(2-cyano-3-methyl)guanidinophenyl)-6-(3-pyridyl)hex-5-enoic acid
-
0.00025 mM, 50% inhibition
(5E)-6-(3-(2-cyano-3-tert-butyl-guanidino)phenyl)-6-(3-pyridyl)hex-5-enoic acid
-
0.000004 mM, 50% inhibition
(5E)-6-(4-(2-cyano-3-cyclopentyl-guanidino)phenyl)-6-(3-pyridyl)hex-5-enoic acid
-
0.00018 mM, 50% inhibition
(5E)-6-(4-(2-cyano-3-cyclopropyl-guanidino)phenyl)-6-(3-pyridyl)hex-5-enoic acid
-
0.0039 mM, 50% inhibition
(5Z)-6-[(2S,4R)-4-(4-Chlorophenylsulphonylamino)-1-(3-pyridylmethyl)-2-pyrrolidinyl]-5-hexenoic acid hydrochloride
-
thromboxane A2 synthetase inhibitor/thromboxane A2-receptor antagonist
(E)-3-[4-(1-Imidazolylmethyl)phenyl]-2-propenoate
-
reversible
(E)-6-[4-(3-tert-butyl-2-cyanoguanidino)phenyl]-6-(3-pyridyl)hex-5-enoic acid
-
trivial name terbogrel
(E)-7-[4-[4-[(benzylamino)carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid
-
0.000025 mM, 50% inhibition
(E)-7-[4-[4-[(pentylamino)carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridiyl)hept-6-enoic acid
-
0.000031 mM, 50% inhibition
(E)-7-[4-[4-[(phenylethylamino)carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid
-
0.0000094 mM, 50% inhibition
(E)-7-[4-[4-[[(2-phenoxybutyl)amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid
-
0.000049 mM, 50% inhibition
(E)-7-[4-[4-[[(2-phenoxyethyl)amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid
-
0.0000026 mM, 50% inhibition
(E)-7-[4-[4-[[(2-phenoxypentyl)amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid
-
0.000049 mM, 50% inhibition
(E)-7-[4-[4-[[(4-cyclohexylbutyl)amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid
-
0.000055 mM, 50% inhibition
(E)-7-[4-[4-[[(4-cyclopropylmethyl)amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid
-
0.000025 mM, 50% inhibition
(E)-7-[4-[4-[[3-(morpholinopropyl)amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid
-
0.0000051 mM, 50% inhibition
(E)-7-[4-[4-[[[2-(benzyloxy)ethyl]amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid
-
0.000048 mM, 50% inhibition
(E)-7-[4-[4-[[[2-(cyclohexylmethoxy)ethyl]amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid
-
0.0000037 mM, 50% inhibition
(E)-7-[4-[4-[[[2-(cyclohexyloxy)ethyl]amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid
-
0.0000033 mM, 50% inhibition
(E)-7-[4-[4-[[[2-(tetrahydropyran-2-ylmethoxy)ethyl]amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid
-
0.0000063 mM, 50% inhibition
(E)-7-[4-[4-[[[3-(1-cyclohexylethoxy)propyl]amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid
-
0.0000012 mM, 50% inhibition
(E)-7-[4-[4-[[[3-(4-methoxyphenyl)propyl]amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid
-
0.0000027 mM, 50% inhibition
(E)-7-[4-[4-[[[3-(cyclohexyloxy)propyl]amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid
-
0.0000042 mM, 50% inhibition
(E)-7-[4-[4-[[[3-[(cis)-4-methoxycyclohexyl]propyl]amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid
-
0.0000029 mM, 50% inhibition
(E)-7-[4-[4-[[[4-(cyclohexyloxy)butyl]amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid
-
0.0000049 mM, 50% inhibition
([5-[2-([[(1E)-phenyl(pyridin-3-yl)methylidene]amino]oxy)ethyl]-7,8-dihydronaphthalen-1-yl]oxy)acetic acid
-
i.e. ONO-1301, in addition to inhibitory activity, application of ONO-1301 significantly attenuates the development of pulmonary fibrosis and improves survival after treatment with bleomycin
1(omega-Carboxylalkyl)imidazoles
-
very potent
-
1-(2-Isopropylphenyl)-imidazole
-
strong
1-Benzylimidazole
-
immobilized enzyme
1-Benzylimidazole
-
-
1-Benzylimidazole
-
-
1-Benzylimidazole
-
special inhibitor of TXS
1-Decylimidazole
-
strong
1-Methyl imidazole
-
-
1-Nonylimidazole
-
strong
1-[2-(4,5,6,7-tetrahydrobenzo[b]furan-4-yl)ethyl]-1H-imidazole
-
0.001 mM, 50% inhibition
1-[2-(4,5,6,7-tetrahydrobenzo[b]furan-4-ylidene)ethyl]-1H-imidazole
-
E isomer, 0.00355 mM, 50% inhibition; Z isomer, 0.0041 mM, 50% inhibition
1-[2-(4,5,6,7-tetrahydrobenzo[b]thiophen-4-yl)ethyl]-1H-imidazole
-
0.0012 mM, 50% inhibition
1-[2-(4,5,6,7-tetrahydrobenzo[b]thiophen-4-ylidene)ethyl]-1H-imidazole
-
E isomer, 0.0017 mM, 50% inhibition; Z isomer, 0.0013 mM, 50% inhibition
1-[2-(benzo[b]thiophen-4-yl)ethyl]-1H-imidazole
-
0.0053 mM, 50% inhibition
1-[3-(4-Benzylhydryl-1-piperazinyl)propyl]-3-(1H-imidazol-1-ylmethyl)-1H-indole-6-carboxylic acid
-
strong thromboxane synthetase inhibition and H1-blocking activity
12L-Hydroperoxy-5,8,10,14-eicosatetraenoic acid
-
0.1 mM, 50% inhibition
15-hydroperoxyeicosatetraenoic acid
-
-
15-Hydroxy-11alpha,9alpha-(epoxymethano)-prosta-5,13-dienoic acid
-
reversible
15-Hydroxy-9alpha,11alpha-peroxidoprosta-5,13-dienoic acid
-
irreversible inactivation during catalysis, protection by (E)-3-[4-(1-imidazolylmethyl)phenyl]-2-propenoate and 15-hydroxy-11alpha,9alpha-(epoxymethano)-prosta-5,13-dienoic acid
1H-Imidazol-1-ylalyl-substituted 3-[2-[(arylsulfonyl)amino]ethyl]benzenepropanoic acid derivatives
-
dual thromboxane synthase inhibitor/thromboxane receptor antagonists
2-Isopropyl-3-nicotinylindole
-
-
2-Isopropyl-3-nicotinylindole
-
potent
2-[4-Carboxy-8-(5-imidazol[1,5-a]pyridinyl)octanoyl]-2,3-dihydro-1H-1-isoindole-1-carboxylic acid
-
-
2-[[1-(Carboxymethyl)-2,3,4,5,-tetrahydro-2-oxo-1H-1-benzazepin-3-yl]amino]-6-[[5-[5-chloro-1-methyl-2-(3-pyridinyl)-1H-indol-3-yl]pentanoyl]amino]hexanoic acid
-
-
2-[[1-(Carboxymethyl)-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3-yl]amino]6-[[5-[5-chloro-1-methyl-2-(3-pyridinyl)-1H-indol-3-yl]pentanoyl](2-hydroxyethyl)amino]hexanoic acid
-
-
2-[[1-(Carboxymethyl)-2,3,4,5-tetrahydro-2-oxo-1H-benzazepin-3-yl]amino]-6-[[1-[5-[5-chloro-1-methyl-2-(3-pyridinyl)1H-indol-3-yl]pentanoyl]piperidin-4-yl]amino]hexanoic acid
-
-
2-[[1-(Carboxymethyl)-2,3,4,5-tetrahydro-2-oxo-1H-benzazepin-3-yl]amino]-6-[[5-[5-chloro-1-methyl-2-(3-pyridinyl)1H-indol-3-yl]pentanoyl][2-(methylamino)ethyl]amino]hexanoic acid
-
-
2-[[1-(Carboxymethyl)-2,3,4,5-tetrahydro-2-oxo-1H-benzazepin-3-yl]amino]-7-[[2-[[5-[5-chloro-1-methyl-2-(3-pyridinyl)1H-indol-3-yl]pentanoyl]amino]ethyl]amino]heptanoic acid
-
-
3-Pyridinylalkyl-substituted 3-[2-[(arylsulfonyl)amino]ethyl]benzenepropanoic acid derivatives
-
dual thromboxane synthase inhibitor/thromboxane receptor antagonists
4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)imidazole
-
trivial name SB203580
4-(Benzylamino)-2-(3'-pyridyl)quinazoline
-
-
4-(Benzylamino)-2-(imidazol-1-yl)-quinazoline
-
-
5-[2-(imidazol-1-yl)-ethyl]-5,6,7,8-tetrahydroquinoline
-
0.00063 mM, 50% inhibition
5-[2-(imidazol-1-yl)ethyl]-1,2,3,4-tetrahydronaphthalene
-
0.0034 mM, 50% inhibition
5-[2-(imidazol-1-yl)ethyl]-7,8-dihydroquinoline
-
0.00029 mM, 50% inhibition
5-[2-(imidazol-1-yl)ethyl]quinoline
-
0.0012 mM, 50% inhibition
5-[3-(imidazol-1-yl)-propyl]-5,6,7,8-tetrahydroquinoline
-
0.0023 mM, 50% inhibition
5-[3-(imidazol-1-yl)-propyl]-7,8-dihydroquinoline
-
0.00068 mM, 50% inhibition
5-[imidazol-1-yl-methyl]-5,6,7,8-tetrahydroquinoline
-
0.002 mM, 50% inhibition
5-[imidazol-1-yl-methyl]-7,8-dihydroquinoline
-
0.0015 mM, 50% inhibition
5E-6-(3-cyanoguanidino)phenyl-6-(3-pyridyl)hex-5-enoic acid
-
0.00043 mM, 50% inhibition
5Z-6[(2S,4R)-4-(4-Chlorophenylsulfonylamino)-1-(3-pyridylmethyl)-2-pyrrolidinyl]-5-hexenoic acid
-
causes marked improvement in the PGI2/TXA2 ratio in diabetic retinopathy by inhibition of thromboxane synthase
7-[(imidazol-1-yl)methyl]isoquinoline
-
0.0054 mM, 50% inhibition
8-[2-(3-Pyridinyl)-1H-indol-1-yl]octanoic acid 1-(carboxymethyl)-3-[(1-carboxy-3-phenylpropyl)amino]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-5-yl ester
-
-
9,11(Epoxymethano) prostanoic acid
-
-
9,11-Azo-15-hydroxyprosta-5,13-dienoic acid
-
-
9,11-Azoprosta-5,13 dienoic acid
-
-
9,11-Azoprosta-5,13-dienoic acid
-
-
9,11-Epoxymethano-15-hydroxy-prosta-5,13-dienoic acid
-
-
9alpha,11alpha-Azo-15-(S)Hydroxyprosta-5(cis)-13(trans)-dienoic acid
-
-
9alpha,11alpha-Methanoepoxy-15(S)-hydroxyprosta-5(cis)-13(trans)-dienoic acid
-
-
9alpha,11alpha-Methanoepoxy-15(S)-hydroxyprosta-5(cis)-13(trans)-dienoic acid
-
no inhibition
9alpha,11alpha-Methanoepoxy-15(S)-hydroxyprosta-5(cis)-13(trans)-dienoic acid
-
weak
Benzydamine
-
-
BM 567
-
i.e. 2-(cyclohexylamino)-5-nitro-N-[(pentylamino)carbonyl]-benzenesulfonamide, 10 microM, a specific inhibitor for thromboxane synthase, decrease the acitivity 2.1fold before diosgenin treatment
carboxyheptal imidazole
-
10 microM, concentration of thromboxane B2 in culture supernatants: reduction of thromboxane B2 in prostate cancer cells PC-3 from 1295 pg/ml to 685 pg/ml, reduction of thromboxane B2 in erythroleukemia cells HEL from 580 pg/ml to 292 pg/ml. In PC-3 cell lysates reduction of thromboxane B2 level by 86%
-
CGS 13080
-
-
Chlorella powder
-
the potent inhibition of cyclooxygenase-2 and thromboxane synthase contribute to the purported anti-inflmammatory and anti-thrombotic effect of Chlorella. This might be exploited for the prevention or treatment of several serious pathologies, including inflammatory diseases, immune and cancer
-
Cu2+
-
1 mM, complete inhibition
CV4151
-
0.0000049 mM, 50% inhibition
-
dazoxiben
-
-
furegrelate
-
0.01 mM, 68% inhibition
furegrelate
-
cultures treated with show a reduced time-dependent increase in cell number compared with vehicle-treated cells. Addition to the growth medium results in reduction in cell invasion and reduction in cell migration.
furegrelate
-
inhibition of thromboxane-A synthase, induces a concentration-dependent increase in cAMP-induced steroidogenic acute regulatory protein StAR concomitantly with a significant increase in steroid hormone production
furegrelate
-
specific inhibitor of thromboxane synthase, i.e. sodium 5-(3-pyridinylmethyl) benzofuran-2-carboxylate
furegrelate
-
specific inhibitor of TXSA
imidazole
-
-
imidazole
-
and derivatives. The potency of 1-substituted imidazoles is increased as the side chain becomes more hydrophobic. Inhibition is competitive with respect to prostaglandin endoperoxide substrate
Indomethacin
-
0.000017 mM, 50% inhibition of PGE2 formation, 0.000013 mM, 50% inhibition of 12-HHT formation
linoleic acid
-
significant inhibition of cyclooxygenase/thromboxane synthase activity, determined by TXB2 production with an ELISA-based assay
N-isopropyl-N'-[(2-(3'-methylphenylamino)-5-nitrobenzene)sulfonyl]urea
-
-
N-isopropyl-N'-[2-(3'-methylphenylamino)-5-nitrobenzenesulfonyl]urea
-
0.001 mM, 95% inhibition
N-pentyl-N'-[(2-cyclohexylamino-5-nitrobenzene)sulfonyl]urea
-
-
N-Substituted 3-(1H-imidazol-1-ylmethyl)indole carboxylic acid derivatives
-
-
-
N-tert-butyl-N'-(2-cyclohexylamino-5-nitrobenzenesulfonyl)urea
-
-
N-tert-butyl-N'-[(2-(4'-methylphenylamino)-5-nitrobenzene)sulfonyl]urea
-
-
N-tert-butyl-N'-[(2-cyclohexylamino-5-nitrobenzene)sulfonyl]urea
-
-
NO
-
irreversible in a concentration-dependent manner
OKY 1581
-
-
ozagrel
-
cultures treated with show a reduced time-dependent increase in cell number compared with vehicle-treated cells. Addition to the growth medium results in reduction in cell invasion and reduction in cell migration.
p-Benzyl-4-[1-oxo-2-(-chlorobenzyl)-3-phenylpropyl]phenyl phosphonate
-
i.e. N-0164
-
p-Benzyl-4-[1-oxo-2-(-chlorobenzyl)-3-phenylpropyl]phenyl phosphonate
-
-
-
paclitaxel
-
45% inhibition at 0.1 mM
prostaglandin H2
-
suicide inactivation
R68070
-
0.0000015 mM, 50% inhibition
radical scavenging glycoprotein
-
-
ridogrel
-
0.000004 mM, 50% inhibition
samixogrel
-
0.000004 mM, 50% inhibition
Sodium 5-(3'-pyridinylmethyl)benzofuran-2-carboxylate
-
immobilized enzyme
Sodium 5-(3'pyridinylmethyl)benzofuran-2-carboxylate
-
-
Sodium p-benzyl-4-[1-oxo-2-(4-chlorobenzyl)-3-phenyl propyl]phenyl phosphonate
-
-
-
thromboxane A2
-
the production of thromboxane A2 by the enzyme is self-limiting, the enzyme is inactivated during the reaction
UK 36248
-
-
-
UK 37,248
-
-
Zn2+
-
1 mM, 50% inhibition
[3-[[Hydroxy[4-[3-methyl-2-(3-pyridinyl)indol-1-yl]butyl]phosphinyl]oxy]2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-1-yl]acetic acid
-
-
[4-[3-Methyl-2-(3-pyridinyl)-1H-indol-1-yl]butyl]phosphonic acid
-
-
[4-[3-Methyl-2-(3-pyridinyl)-1H-indol-1-yl]butyl]phosphonic acid monoethyl ester
-
-
linolelaidic acid
-
significant inhibition of cyclooxygenase/thromboxane synthase activity, determined by TXB2 production with an ELISA-based assay
additional information
-
overview
-
additional information
-
the enzyme is insensitive to sulfhydryl reagents and thiols
-
additional information
-
the enzyme is not affected by nonsteroidal antiinflammatory agents
-
additional information
-
development of a screening assay for the in vitro evaluation of thromboxane A2 synthase inhibitors. Inhibitors of thromboxane synthase are regarded as potentially useful agents in the treatment of cardiovascular diseases and in the prevention of tumor cell metastases
-
additional information
-
dual angiotensin converting enzyme/thromboxane synthase inhibitors
-
additional information
-
design of new potential dual blocker which inhibits thromboxane synthase and antagonizes thromboxane A2 receptor
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
diosgenin
-
10 microM increases cyclooxygenase-2 and thromboxane synthase expression and activities in HEL cells, 3.5fold at 96 h and 4.5fold at 144 h
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.02
-
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
-
23C, pH 7.5
0.021
-
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
-
recombinant TXAS
0.022
-
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
-
native TXAS
0.071
-
15-hydroperoxyeicosatetraenoic acid
-
pH 7.5, 23C, heterolytic cleavage
0.087
-
15-hydroperoxyeicosatetraenoic acid
-
pH 7.5, 23C, homolytic cleavage
0.012
-
15-hydroxy-9alpha,11alpha-peroxiprosta-5,13-dienoic acid
-
-
-
0.023
-
prostaglandin G2
-
prostaglandin H3
0.024
-
Prostaglandin H1
-
-
0.002
-
prostaglandin H2
-
immobilized enzyme
0.004
-
prostaglandin H2
-
-
0.0053
-
prostaglandin H2
-
soluble enzyme
0.01
-
prostaglandin H2
-
-
0.0207
-
prostaglandin H2
-
-
0.022
-
prostaglandin H2
-
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.017
-
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
-
recombinant TXAS
28.2
-
prostaglandin G2
-
-
26.7
-
prostaglandin H2
-
-
27.1
-
prostaglandin H2
-
-
20.4
-
Prostaglandin H3
-
-
59.4
-
Prostaglandin H3
-
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1
-
Zn2+
-
-
0.1
-
12L-Hydroperoxy-5,8,10,14-eicosatetraenoic acid
-
-
additional information
-
Chlorella powder
-
3.32 microg/ml, tested in an in vitro assay system
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.00515
-
-
-
0.231
-
-
-
0.255
-
-
-
0.259
-
-
-
1.15
-
-
-
2.95
-
-
recombinant TXAS
24.1
-
-
-
additional information
-
-
application of monoclonal antibodies to develop a tandem immunoradiometric assay
additional information
-
-
accumulation of thromboxane B2 in the culture supernatants of prostate cancer cells PC-3 1295 pg/ml compared with 580 pg/ml in supernatants from erythroleukemia cells HEL and 30 pg/ml from prostate cancer cells DU145. In cell lysates from PC-3 cells 22.5 pg thromboxane B2 per million cells, in cell lysates from prostate cancer cells DU145 0.475 pg per million cells
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.4
-
-
broad
7.5
-
-
-
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5
8.5
-
very little pH-dependence between pH 5-8.5, above pH 9.0 the reaction is significantly depressed
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
30
-
-
-
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
20
37
-
activity at 37C is not significantly higher than at 20C
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
thromboxane synthase, prostaglandin cyclase and cyclooxygenase COX-1 are widely distributed throughout normal aortic endothelium
Manually annotated by BRENDA team
-
atherosclerotic aorta
Manually annotated by BRENDA team
-
TXAS is expressed in the atherosclerotic lesion, associated with increased inflammatory cells, in particular M2 polarized macrophages
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
bladder cancer cell lines T24 and TCC-SUP
Manually annotated by BRENDA team
-
colorectal carcinoma
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
human erythroleukemia cells
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
in normal lung tissue, TXS is moderately expressed in bronchial epithelial cells and weakly expressed in vascular smooth muscle cells
Manually annotated by BRENDA team
-
mouse leydig cells
Manually annotated by BRENDA team
-
the higher staining intensities are in the ganglion cell and inner plexiform layers and in the outer plexiform layer, with more staining in the inner nuclear layer than in the outer nuclear layer
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
58000
-
-
gel filtration
60000
-
-
transmembrane TXAS, considered to be an atypical memeber of the cytochrome P450 superfamily as lacks its minooxygenase activity
60000
-
-
SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 53000, SDS-PAGE
?
-
x * 58800, SDS-PAGE
?
-
x * 58000, SDS-PAGE
monomer
-
x * 58000, SDS-PAGE
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4.5
-
-
unstable below
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
52
-
-
5 min, 50% loss of activity
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
immobilized enzyme is inactivated at pH 3.0
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-70C, stable for several months
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
partial
-
intrinsic membrane protein, detergent treatment is necessary
-
one-step immunoaffinity purification
-
partial
-
recombinant His-tagged TXAS
-
recombinant TXAS
-
recombinant TXAS, Ni-NTA, column, DEAE-column, Octyl-column
-
immunoaffinity purification
-
partial
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
characterization of the gene TBXAX1 encoding thromboxane synthase
-
expression in Escherichia coli
-
overexpression in Escherichia coli
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
inhibition of platelet TXA2 generation (acetylsalicylic acid), lowering of cholesterol (statins), inhibition of platelet aggregation (clopidogrel), or promoting vasodilatation (dipyridamole) has no effect on TXAS mRNA expression levels
-
smokers tend to express more TxAS than nonsmokers
-
an overall increase in TXS expression is observed in tumor tissues relative to normal, increased TXS expression at mRNA level is reported in renal cell carcinoma, breast carcinoma, prostate cancer and uterine cancer when compared with matched normal tissues
-
TXAS increases in atherosclerotic lesions of patients with recent symptoms of thrombotic events
-
TXSA is upregulated in human glial tumors
-
TNF-alpha, U46619 and 8-isoprostane F2alpha and hypoxia all augment TXAS protein expression. NADPH oxidase-1 (but not NADPH oxidase-4) gene silencing, as well as picotamide and iloprost inhibit the increase in TXAS expression and activity
-
4 weeks of streptozotocin-induced diabetes do not increase the retinal levels of TxS
-
inhibition of platelet TXA2 generation (acetylsalicylic acid), lowering of cholesterol (statins), inhibition of platelet aggregation (clopidogrel), or promoting vasodilatation (dipyridamole) has no effect on TXAS mRNA expression levels
-
after 8 and 16 weeks on the fat diet, aortic arches from low-density lipoprotein receptor deficient mice show a significant increase in TXAS mRNA level when compared with control
-
TXAS mRNA expression is increased within the vascular wall in mouse models of atherosclerosis with advanced lesions
-
4 weeks of streptozotocin-induced diabetes do not increase the retinal levels of TxS
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
A408L
-
42% of wild-type activity
A415V
-
82% of wild-type activity
C480H
-
no activity
C480S
-
no activity
C480Y
-
no activity
E134D
-
35% of wild-type activity
E135D
-
123% of wild-type activity
E414D
-
39% of wild-type activity
F409Y
-
42% of wild-type activity
F411Y
-
38% of wild-type activity
L488P
-
in alpha-helix, indroducing a coil in the secondary structure, crucial for enzyme activity
L83P
-
in beta-sheet, indroducing a coil in the secondary structure, crucial for enzyme activity
N110I
-
no activity
Q482W
-
changing an aliphatic amino acid with low steric hindrance into an aromatic amino acid with high steric hindrance in the vicinitx of the catalytic site, modifying the interaction of the enzyme-substarte complex, crucial for enzyme activity
R137A
-
2% of wild-type activity
R137K
-
5% of wild-type activity
R410G
-
46% of wild-type activity
R413K
-
1% of wild-type activity
R431E
-
decreased enzyme activity, 1% residual activity
R431K
-
decreased enzyme activity, 1% residual activity
R478A
-
no activity
T412S
-
41% of wild-type activity
V136A
-
69% of wild-type activity
W133F
-
2% of wild-type activity
additional information
-
treatment with enzyme-specific RNAi results in increased levels of steroidogenic acute regulatory protein StAR and steroidogenesis. Inhibition of enzyme activity reduces the levels of StaR transcriptional repressor DAX-1
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
analysis
-
immobilized enzyme is sufficiently stable to be used as a model for studying the properties of the enzyme
medicine
-
thromboxane A2 may somehow mediate coughing induced by the angiotensin converting enzyme inhibitors. Patients on angiotensin converting enzyme inhibitors who develop cough may benefit from thromboxane A2 synthetase inhibitors
medicine
-
improvement of the renal function with the selective thromboxane A2 synthetase inhibitor (+/-)-6-(1-imidazolylmethyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid hydrochloride hemihydrate
medicine
-
the thromboxane A2 synthetase inhibitor/thromboxane A2-receptor antagonist (5Z)-6-[(2S,4R)-4-(4-chlorophenylsulfonylamino)-1-(3-pyridylmethyl)-2-pyrrolidinyl]-5-hexenoic acid hydrochloride may be of clinical relevance for the prevention or treatment of th
medicine
-
possible role in the regulation of prostate cancer cell migration
medicine
-
TXAS mRNA expression was found to be an independent prognostic marker for patients with bladder cancer
medicine
-
thromboxane-A synthase protein is consistently upregulated in the cancer tissues from patients with colorectal carcinoma and also highly expressed in colonic cancer cell lines. Depletion of enzyme protein by antisense oligonucleotide inhibits proliferation of cancer cells
medicine
-
TBXAS1 gene polymorphisms are a marker for development of cerebral infarction, especially small-artery occlusion type in Korean population
medicine
-
the targeted inhibition of TXSA activity improves the efficiency of conventional alkylation chemotherapy in vivo
pharmacology
-
development of a screening assay for the in vitro evaluation of thromboxane A2 synthase inhibitors. Inhibitors of thromboxane synthase are regarded as potentially useful agents in the treatment of cardiovascular diseases and in the prevention of tumor cell metastases
medicine
-
in addition to inhibitory activity, application of ONO-1301, i.e. ([5-[2-([[(1E)-phenyl(pyridin-3-yl)methylidene]amino]oxy)ethyl]-7,8-dihydronaphthalen-1-yl]oxy)acetic acid, significantly attenuates the development of pulmonary fibrosis and improves survival after treatment with bleomycin
pharmacology
-
the thromboxane A2 synthetase inhibitor 1-[3-(4-benzylhydryl-1-piperazinyl)propyl]-3-(1H-imidazol-1-ylmethyl)-1H-indole-6-carboxylic acid is a candidate anti-asthmatic drug
analysis
-
application of monoclonal antibodies to develop a tandem immunoradiometric assay