Any feedback?
Information on EC 1.1.1.188 - prostaglandin-F synthase and Organism(s) Bos taurus and UniProt Accession P16116
for references in articles please use BRENDA:EC1.1.1.188Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
1.1.1.188 prostaglandin-F synthaseIUBMB Comments
Reduces prostaglandin D2 and prostaglandin H2 to prostaglandin F2; prostaglandin D2 is not an intermediate in the reduction of prostaglandin H2. Also catalyses the reduction of a number of carbonyl compounds, such as 9,10-phenanthroquinone and 4-nitroacetophenone.
Specify your search results
Word Map
- 1.1.1.188
- aldose
- endometrium
-
estrous
- mpges-1
-
reductase-like
- akr1b3
- synthase-2
-
rho-crystallins
-
ptgfr
-
luteotropic
-
9-ketoreductase
-
alpha-hsds
-
bitch
- medicine
- chlordecone
- synthesis
- drug development
- pharmacology
- molecular biology
The taxonomic range for the selected organisms is: Bos taurus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Reaction Schemes
Synonyms
pgfs, akr1b7, prostaglandin f synthase, pgf synthase, vas deferens protein, prostamide/pgf synthase, prostaglandin f synthetase, p100/11e, akr1cl, pgd2 11-ketoreductase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
NADPH-dependent prostaglandin D2 11-keto reductase
-
-
-
-
PGD2 11-ketoreductase
PGF synthase
PGF2alpha synthase
-
-
-
-
PGFSI
-
-
-
-
PGFSII
-
-
-
-
prostaglandin 11-keto reductase
-
-
-
-
prostaglandin 11-ketoreductase
-
-
-
-
prostaglandin D2-ketoreductase
-
-
-
-
prostaglandin F synthase
prostaglandin F synthetase
-
-
-
-
prostaglandin-D2 11-reductase
-
-
-
-
reductase, 15-hydroxy-11-oxoprostaglandin
-
-
-
-
synthetase, prostaglandin F2alpha
-
-
-
-
additional information
-
enzyme belongs to the AKR aldo-keto-reductase superfamily
PGD2 11-ketoreductase
-
-
-
-
PGF synthase
-
-
-
-
prostaglandin F synthase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate:NADP+ 11-oxidoreductase
Reduces prostaglandin D2 and prostaglandin H2 to prostaglandin F2; prostaglandin D2 is not an intermediate in the reduction of prostaglandin H2. Also catalyses the reduction of a number of carbonyl compounds, such as 9,10-phenanthroquinone and 4-nitroacetophenone.
CAS REGISTRY NUMBER
COMMENTARY
55976-95-9
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+
-
-
-
-
?
(5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH
(5Z,13E)-(15S)-9alpha,11beta,15-trihydroxyprosta-5,13-dienoate + NADP+
-
-
-
-
?
4-nitrobenzaldehyde + NADPH
4-nitrobenzyl alcohol + NADP+
-
-
-
-
?
prostaglandin H2 + NADPH + H+
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+
-
-
-
-
?
prostaglandin H2 + NADPH + H+
9alpha,11alpha-prostaglandin F2alpha + NADP+
-
-
-
-
?
9,10-phenanthrenequinone + NADPH
?
-
-
-
-
?
prostaglandin D2 + NADPH + H+
prostaglandin 9alpha,11beta-F2 + NADP+
-
-
product is involved in bronchial, vascular, and arterial smooth muscle contraction, product inhibits platelet aggregation and activates urinary excretion, i.e. 11-epi PGF2alpha
-
?
prostaglandin D2 + NADPH + H+
prostaglandin 9alpha,11beta-F2 + NADP+
-
amino acid residues Arg27, Arg91, His170, Arg223, and Asn306 are involved in substrate binding
-
-
?
prostaglandin H2 + NADPH + H+
prostaglandin F2alpha + NADP+
-
enzyme also shows PGH2 9-,11-endoperoxide reductase activity
-
-
?
prostaglandin H2 + NADPH + H+
prostaglandin F2alpha + NADP+
-
His170 is involved in binding, and Asn306 is critical for catalytic activity
-
-
?
additional information
?
-
PGFS activity of the recombinant proteins is evaluated using an assay based on in situ generation of the precursor of prostaglandin PGH2 biosynthesis. PGF2alpha is measured by ELISA. Comparisons of PGFS activity of recombinant bovine and human endometrial AKRs, overview
-
-
?
additional information
?
-
-
PGFS activity of the recombinant proteins is evaluated using an assay based on in situ generation of the precursor of prostaglandin PGH2 biosynthesis. PGF2alpha is measured by ELISA. Comparisons of PGFS activity of recombinant bovine and human endometrial AKRs, overview
-
-
?
additional information
?
-
-
two different active sites, one for the endoperoxide group of prostaglandin H2 and the other one for the keto group of prostaglandin D2 and other carbonyl compounds
-
-
?
additional information
?
-
-
two different active sites, one for the endoperoxide group of prostaglandin H2 and the other one for the keto group of prostaglandin D2 and other carbonyl compounds
-
-
?
additional information
?
-
-
two different active sites, one for the endoperoxide group of prostaglandin H2 and the other one for the keto group of prostaglandin D2 and other carbonyl compounds
-
-
?
additional information
?
-
-
two different active sites, one for the endoperoxide group of prostaglandin H2 and the other one for the keto group of prostaglandin D2 and other carbonyl compounds
-
-
?
additional information
?
-
-
the enzyme is important for the production of lyteolytic prostaglandin F2alpha in the endometrium of cows, regulatory mechanisms, overview
-
-
?
additional information
?
-
-
the liver-type isozyme possesses two catalytic centres and a broad substrate specificity, D-xylose is a poor substrate, no activity with prostaglandin A1, prostaglandin B2, prostaglandin E2, 4-carboxybenzaldehyde, testosterone, 2,6-dichloroindophenol, D-glucose, D-glucuronic acid, and potassium ferricyanide, overview, the enzyme also exhibits aldose reductase, EC 1.1.1.21, and alcohol dehydrogenase, EC 1.1.1.1, activities, respectively
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
prostaglandin D2 + NADPH + H+
prostaglandin 9alpha,11beta-F2 + NADP+
-
-
product is involved in bronchial, vascular, and arterial smooth muscle contraction, product inhibits platelet aggregation and activates urinary excretion
-
?
prostaglandin H2 + NADPH + H+
prostaglandin F2alpha + NADP+
-
enzyme also shows PGH2 9-,11-endoperoxide reductase activity
-
-
?
additional information
?
-
-
the enzyme is important for the production of lyteolytic prostaglandin F2alpha in the endometrium of cows, regulatory mechanisms, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
9,10-phenanthrenequinone
-
competitive inhibitor of the reduction of prostaglandin D2, not of prostaglandin H2
9,10-phenanthrenequinone
-
competitive inhibition of PGD2 but not of PGH2 reduction
HgCl2
-
IC50 = 0.3 mM, the liver-type isozyme is 2fold less sensitive than the lung-type isozyme
interferon tau
-
recombinant ovine interferon tau down-regulates mRNA gene expression of the prostaglandin F synthase at a concentration of 0.000001 mg/ml
-
interferon tau
-
recombinant bovine interferon tau down-regulates mRNA gene expression of the prostaglandin F synthase after stimulation with oxytocin
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
chloride
-
stimulates the reduction of prostaglandin D2 and carbonyl compounds, but had no effect on prostaglandin H2 reduction
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.01
prostaglandin PGH2
-
recombinant liver-type isozyme, mutants R91Q, R223L and N306Y, 37°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0009
9,10-phenanthrenequinone
-
37°C, liver-type isozyme, versus prostaglandin D2
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.3
HgCl2
Bos taurus
-
IC50 = 0.3 mM, the liver-type isozyme is 2fold less sensitive than the lung-type isozyme
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.041
purified recombinant enzyme, pH 7.0, 25°C, in presence of 0.05 mM 9,10-phenanthrenequinone
0.003
0.046
0.089
0.095
0.31
0.339
additional information
additional information
-
expression levels in the placentome of pregnant cows at different developmental stages
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
the bovine endometrium produces huge amounts of PGF2alpha
-
expression levels in uninucleated trophoblasts of the placentome of pregnant cows, especially chorionic plate and apical tertiary villi, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
no liver-type isozyme in mitochondrion, nucleus, or Golgi apparatus
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
AKR1B1 is able to produce PGF2alpha in the endometrium in addition toAKR1C3. The PGF synthase activity of AKR1B1 proves to be much higher than that of AKR1C3
physiological function
PGF2alpha plays important roles in the regulation of ocular pressure, renal absorption, cardiovascular function, adipocyte differentiation, and female reproductive function. Role of bovine AKR1B1, previously known as AKR1B5, in the formation of PGF2alpha from PGH2 in the bovine endometrium
physiological function
-
lentiviral vector-mediated delivery of the prostaglandin F synthase (PGFS) gene resultes in long-term reduction of intraocular pressure and may eliminate off-target tissue effects and the need for daily topical PGF2alpha self-administration
additional information
additional information
comparisons of PGFS activity of recombinant bovine and human endometrial AKRs, overview
additional information
-
comparisons of PGFS activity of recombinant bovine and human endometrial AKRs, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
36000
36666
-
1 * 36666, lung-type isozyme, sequence calculation, 1 * 36742, liver-type isozyme, sequence calculation
36670
36740
36742
-
1 * 36666, lung-type isozyme, sequence calculation, 1 * 36742, liver-type isozyme, sequence calculation
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
monomer
-
1 * 36666, lung-type isozyme, sequence calculation, 1 * 36742, liver-type isozyme, sequence calculation
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H170C
K225S
N306Y
R223L
R27E
R91Q
S301R
additional information
-
lentiviral vector-mediated delivery of the prostaglandin F synthase (PGFS) gene to the eye. Expression of myc-tagged GFP-PGFS in non-human primate eyes via FIV vector leads to a significant reduction of intraocular pressure, IOP, the GFP-tag can still be detected after 48-52 weeks, the decrease in IOP lasts for 5 months. The IOP decrease is not as much as seen with topical prostaglandin therapy in monkey eyes, method evaluation. In human eye a single injection of lentiviral vectors into either the anterior or posterior chambers can induce a transient uveitis. Following transcorneal injection of vector into the living monkey eyes, biomicroscopic examination initially reveal cells and flare in the anterior chamber and some corneal haze that is largely resolved by 3 weeks post injection. This is not due to bacterial endotoxin contamination of the vector preparations and is likely the result of activation of innate viral sensors in the eye
H170C
-
site-directed mutagenesis, increased Km for prostaglandin PGD2 and 8fold decreased Km for prostaglandin PGH2 compared to the wild-type enzyme
K225S
-
site-directed mutagenesis, slightly increased Km for prostaglandin PGD2 and PGH2 compared to the wild-type enzyme
N306Y
-
site-directed mutagenesis, increased Km for prostaglandin PGD2 and 5fold increased activity with prostaglandin PGH2 compared to the wild-type enzyme
R223L
-
site-directed mutagenesis, increased Km for prostaglandin PGD2 compared to the wild-type enzyme
R27E
-
site-directed mutagenesis, increased Km for prostaglandin PGD2 compared to the wild-type enzyme
R91Q
-
site-directed mutagenesis, increased Km for prostaglandin PGD2 compared to the wild-type enzyme
S301R
-
site-directed mutagenesis, slightly increased Km for prostaglandin PGD2 and PGH2 compared to the wild-type enzyme
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
100
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
several freezing and thawing cycles reduce the activity of stored purified liver-type isozyme by 50%
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80°C, concentration 1.5 mg per ml 10 mM potassium phosphate buffer pH 7.0, stable for several months
-
-80°C, purified liver-type isozyme at 1.5 mg/ml in 10 mM potassium phosphate, pH 7.0, stable for several months, several freezing and thawing cycles reduce the activity by 50%
-
25°C, concentration 1.5 mg per ml 10 mM potassium phosphate buffer pH 7.0, 80-90% activity, 1 month
-
4°C, concentration 1.5 mg per ml 10 mM potassium phosphate buffer pH 7.0, 80-90% activity, 1 month
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
native liver-type isozyme from liver, 342fold to homogeneity by ammonium sulfate fractionation, anion exchange and adsorption chromatography
-
recombinant wild-type liver-type isoyzme and mutant enzymes from COS-7 cells, to homogeneity
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene AKR1B1, recombinant expression of N-terminally His8-tagged enzyme in Escherichia coli strain BL21(DE3)pLysS
expression of myc-tagged GFP-PGFS in non-human primate eyes via FIV vector leading to a significant reduction of intraocular pressure, IOP, the GFP-tag can still be detected after 48-52 weeks, the decrease in IOP lasted for 5 months, method evaluation
-
liver-type isozyme, full length cDNA from cDNA library, DNA and amino acid sequence determination and analysis, transient expression of wild-type and mutant enzymes in COS-7 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
AKR1B1 expression is induced by interleukin-1beta leading to a higher production of prostaglandin F2alpha
after treatment with estradiol, PGFS mRNA expression increases 2.9fold after 4 h and reaches a maximum level of 3.8-4.4fold after 8 to 24 h
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
lentiviral vector-mediated delivery of the prostaglandin F synthase (PGFS) gene resultes in long-term reduction of intraocular pressure and may eliminate off-target tissue effects and the need for daily topical PGF2alpha self-administration
medicine
-
estradiol causes a short-term increase in cyclooxygenase COX-2, which stimulates PGE2 and PGF2alpha secretion, and a subsequent decrease in COX-2 and an increase in cyclooxygenase COX-1 produce a high PGE2 : PGF2alpha ratio
medicine
-
significantly higher expression of the prostaglandin-endoperoxide synthase PTGS 2 gene is detected in repeat-breeding cows with subclinical endometritis, whereas there is no significant difference in the expression of prostaglandin F2alpha synthase PTGFS and prostaglandin E2 microsomal synthase mPTGES 1 mRNAs between repeat-breeding cows with subclinical endometritis and those without it
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Endo, K.; Fukui, M.; Mishima, M.; Watanabe, K.
Metabolism of vitamin A affected by prostaglandin F synthase in contractile interstitial cells of bovine lung
Biochem. Biophys. Res. Commun.
287
956-961
2001
Bos taurus
Asselin, E.; Fortier, M.A.
Detection and regulation of the messenger for a putative bovine endometrial 9-keto-prostaglandin E2 reductase: effect of oxytocin and interferon-tau
Biol. Reprod.
62
125-131
2000
Bos taurus
Suzuki, T.; Fujii, Y.; Miyano, M.; Chen, L.Y.; Takahashi, T.; Watanabe, K.
cDNA cloning, expression, and mutagenesis study of liver-type prostaglandin F synthase
J. Biol. Chem.
274
241-248
1999
Bos taurus
Xiao, C.W.; Murphy, B.D.; Sirois, J.; Goff, A.K.
Down-regulation of oxytocin-induced cyclooxygenase-2 and prostaglandin F synthase expression by interferon-.tau. in bovine endometrial cells
Biol. Reprod.
60
656-663
1999
Bos taurus
Fukui, M.; Fujimoto, T.; Watanabe, K.; Endo, K.; Kuno, K.
Prostaglandin F synthase is localized to contractile interstitial cells in bovine lung
J. Histochem. Cytochem.
44
251-257
1996
Bos taurus
Barski, O.A.; Watanabe, K.
Kinetic mechanism of ketoreductase activity of prostaglandin F synthase from bovine lung
FEBS Lett.
320
107-110
1993
Bos taurus
Kuchinke, W.; Barski, O.; Watanabe, K.; Hayaishi, O.
A lung type prostaglandin F synthase is expressed in bovine liver: cDNA sequence and expression in E. coli
Biochem. Biophys. Res. Commun.
183
1238-1246
1992
Bos taurus
Chen, L.Y.; Watanabe, K.; Hayaishi, O.
Purification and characterization of prostaglandin F synthase from bovine liver
Arch. Biochem. Biophys.
296
17-26
1992
Bos taurus
Watanabe, K.; Fujii, Y.; Ohkubo, H.; Kuramitsu, S.; Kagamiyama, H.; Nakanishi, S.; Hayaishi, O.
Expression of bovine lung prostaglandin F synthase in Escherichia coli
Biochem. Biophys. Res. Commun.
181
272-278
1991
Bos taurus
Watanabe, K.; Fujii, Y.; Nakayama, K.; Ohkubo, H.; Kuramitsu, S.; Hayashi, H.; Kagamiyama, H.; Nakanishi, S.; Hayaishi, O.
Cloning, nucleotide sequence and gene expression of bovine lung prostaglandin F synthetase
Adv. Prostaglandin Thromboxane Leukot. Res.
19
462-465
1988
Bos taurus
Watanabe, K.; Fujii, Y.; Nakayama, K.; Ohkubo, H.; Karamitsu, S.; Kagamiyama, H.; Nakanishi, S.; Hayaishi, O.
Structural similarity of bovine lung prostaglandin F synthase to lens epsilon-crystallin of the European common frog
Proc. Natl. Acad. Sci. USA
85
11-15
1988
Bos taurus, Rana temporaria
Watanabe, K.; Yoshida, R.; Shimizu, T.; Hayaishi, O.
Enzymatic formation of prostaglandin F2 alpha from prostaglandin H2 and D2. Purification and properties of prostaglandin F synthetase from bovine lung
J. Biol. Chem.
260
7035-7041
1985
Bos taurus
Suzuki-Yamamoto, T.; Fujii, Y.; Miyano, M.; Chen, L.Y.; Takahashi, T.; Yokoi, H.; Tsuruo, Y.; Ishimura, K.; Watanabe, K.
cDNA cloning and mutagenesis study of liver-type prostaglandin F synthase, and identification of the prostaglandin F producing cells in the liver
Adv. Exp. Med. Biol.
507
263-268
2002
Bos taurus
Watanabe, K.
Prostaglandin F synthase
Prostaglandins
68-69
401-407
2002
Bos taurus, Oryctolagus cuniculus, Ovis aries, Homo sapiens, Rattus norvegicus, Trypanosoma brucei
Schuler, G.; Teichmann, U.; Kowalewski, M.P.; Hoffmann, B.; Madore, E.; Fortier, M.A.; Klisch, K.
Expression of cyclooxygenase-II (COX-II) and 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD)/prostaglandin F-synthase (PGFS) in bovine placentomes: implications for the initiation of parturition in cattle
Placenta
27
1022-1029
2006
Bos taurus
Lee, E.S.; Rasmussen, C.A.; Filla, M.S.; Slauson, S.R.; Kolb, A.W.; Peters, D.M.; Kaufman, P.L.; Gabelt, B.T.; Brandt, C.R.
Prospects for lentiviral vector mediated prostaglandin F synthase gene delivery in monkey eyes in vivo
Curr. Eye Res.
39
859-870
2014
Bos taurus
Lacroix Pepin, N.; Chapdelaine, P.; Fortier, M.A.
Evaluation of the prostaglandin F synthase activity of human and bovine aldo-keto reductases: AKR1A1s complement AKR1B1s as potent PGF synthases
Prostaglandins Other Lipid Mediat.
106
124-132
2013
Bos taurus (P16116), Bos taurus, Homo sapiens (P15121), Homo sapiens
Janowski, T.; Baranski, W.; Lukasik, K.; Skarzynski, D.; Zdunczyk, S.; Malinowska, K.
Endometrial mRNA expression of prostaglandin synthase enzymes PTGS 2, PTGFS and mPTGES 1 in repeat-breeding cows with cytologically determined endometritis
Acta Vet. Hung.
65
96-104
2017
Bos taurus
EXTERNAL LINKS (specific for EC-Number 1.1.1.188)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
