Information on EC 1.1.1.188 - prostaglandin-F synthase and Organism(s) Homo sapiens

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Homo sapiens


The taxonomic range for the selected organisms is: Homo sapiens

The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
1.1.1.188
-
RECOMMENDED NAME
GeneOntology No.
prostaglandin-F synthase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+ = (5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH + H+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
arachidonic acid metabolism
-
-
Arachidonic acid metabolism
-
-
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 hide
55976-95-9
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
-
comparisons of PGFS activity of recombinant bovine and human endometrial AKRs, overview
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+
(5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH + H+
show the reaction diagram
-
-
-
-
?
(5Z,13E)-(15S)-9alpha,11beta,15-trihydroxyprosta-5,13-dienoate + NADP+
(5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH + H+
show the reaction diagram
-
-
-
-
?
(5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+
show the reaction diagram
-
-
-
-
?
(5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH
(5Z,13E)-(15S)-9alpha,11beta,15-trihydroxyprosta-5,13-dienoate + NADP+
show the reaction diagram
-
-
-
-
?
4-nitrobenzaldehyde + NADPH
4-nitrobenzyl alcohol + NADP+
show the reaction diagram
-
-
-
-
?
4-nitrobenzaldehyde + NADPH + H+
(4-nitrophenyl)methanol + NADP+
show the reaction diagram
-
-
-
-
?
5beta-androstane-3,17-dione + NADPH
5beta-androstan-3alpha-ol-17-one + NADP+
show the reaction diagram
-
-
-
-
r
9,10-phenanthrenequinone + NADPH
?
show the reaction diagram
9,10-phenanthrenequinone + NADPH
? + NADP+
show the reaction diagram
-
-
-
-
?
9,10-phenanthrenequinone + NADPH + H+
?
show the reaction diagram
-
-
-
-
?
androst-4-ene-3,17-dione + NADPH
? + NADP+
show the reaction diagram
-
-
-
-
?
prostaglandin D2 + NADP+
9alpha,11beta-prostaglandin F2 + NADPH
show the reaction diagram
-
-
-
-
?
prostaglandin D2 + NADP+
9alpha11beta-prostaglandin F2 + NADPH
show the reaction diagram
-
-
-
-
?
prostaglandin D2 + NADPH
9alpha,11alpha-prostaglandin F2alpha + NADP+
show the reaction diagram
-
reaction via formation of the endoperoxide ethanolamide intermediate prostaglandin H2
-
-
?
prostaglandin D2 + NADPH
9alpha,11beta-prostaglandin F2alpha + NADP+
show the reaction diagram
-
-
-
-
r
prostaglandin D2 + NADPH
9alpha,11beta-prostaglandin F2alphabeta + NADP+
show the reaction diagram
-
-
-
-
?
prostaglandin D2 + NADPH
prostaglandin F2alpha + NADP+
show the reaction diagram
-
-
-
?
prostaglandin D2 + NADPH + H+
9-alpha,11-beta-prostaglandin F2 + NADP+
show the reaction diagram
-
-
-
-
?
prostaglandin D2 + NADPH + H+
9alpha,11beta-prostaglandin F2 + NADP+
show the reaction diagram
prostaglandin D2 + NADPH + H+
prostaglandin 9alpha,11beta-F2 + NADP+
show the reaction diagram
prostaglandin D2 ethanolamide + NADPH
prostaglandin 9alpha,11beta-F2 ethanolamide + NADP+
show the reaction diagram
i.e. prostamide D2
i.e. 91lpha,11beta-prostamide F2
-
?
prostaglandin H2 + NADP+
prostaglandin F2alpha + NADPH + H+
show the reaction diagram
-
-
-
-
?
prostaglandin H2 + NADPH
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+
show the reaction diagram
-
-
-
-
?
prostaglandin H2 + NADPH
9alpha,11alpha-prostaglandin F2alpha + NADP+
show the reaction diagram
-
-
-
-
?
prostaglandin H2 + NADPH
prostaglandin 9alpha,11beta-F2 + NADP+
show the reaction diagram
-
-
-
?
prostaglandin H2 + NADPH
prostaglandin D2 + NADP+
show the reaction diagram
-
-
-
-
?
prostaglandin H2 + NADPH
prostaglandin F2alpha + NADP+
show the reaction diagram
prostaglandin H2 + NADPH + H+
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+
show the reaction diagram
aldo-keto reductase has prostaglandin F2alpha synthase activity. AKR1B1 is a more efficient prostaglandin F2alpha synthase than AKR1C3
-
-
?
prostaglandin H2 + NADPH + H+
9alpha,11beta-prostaglandin F2 + NADP+
show the reaction diagram
-
-
-
-
?
prostaglandin H2 + NADPH + H+
prostaglandin F2alpha + NADP+
show the reaction diagram
prostamide D2 + NADPH + H+
9alpha,11beta-prostamide F2 + NADP+
show the reaction diagram
-
-
-
?
prostamide H2 + NADPH + H+
prostamide F2alpha + NADP+
show the reaction diagram
-
about 70% of prostamide H2 is converted to prostamide F2alpha after 2 min at 37C
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+
(5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH + H+
show the reaction diagram
-
-
-
-
?
(5Z,13E)-(15S)-9alpha,11beta,15-trihydroxyprosta-5,13-dienoate + NADP+
(5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH + H+
show the reaction diagram
-
-
-
-
?
prostaglandin D2 + NADP+
9alpha,11beta-prostaglandin F2 + NADPH
show the reaction diagram
-
-
-
-
?
prostaglandin D2 + NADPH
9alpha,11beta-prostaglandin F2alphabeta + NADP+
show the reaction diagram
-
-
-
-
?
prostaglandin D2 + NADPH + H+
9-alpha,11-beta-prostaglandin F2 + NADP+
show the reaction diagram
-
-
-
-
?
prostaglandin D2 + NADPH + H+
prostaglandin 9alpha,11beta-F2 + NADP+
show the reaction diagram
-
-
product is involved in bronchial, vascular, and arterial smooth muscle contraction, product inhibits platelet aggregation and activates urinary excretion
-
?
prostaglandin H2 + NADP+
prostaglandin F2alpha + NADPH + H+
show the reaction diagram
-
-
-
-
?
prostaglandin H2 + NADPH
9alpha,11alpha-prostaglandin F2alpha + NADP+
show the reaction diagram
-
-
-
-
?
prostaglandin H2 + NADPH
prostaglandin D2 + NADP+
show the reaction diagram
-
-
-
-
?
prostaglandin H2 + NADPH
prostaglandin F2alpha + NADP+
show the reaction diagram
-
-
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADP+
NADPH
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(5Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(1E,3S)-3-hydroxy-5-phenylpent-1-en-1-yl]cyclopentyl]-N-ethylhept-5-enamide
-
bimatoprost
(5Z)-7-[(1R,4S,5S,6R)-6-[(1E)-oct-1-en-1-yl]-2-azabicyclo[2.2.1]hept-5-yl]hept-5-enoic acid
-
ONO1370
(5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-2-azabicyclo[2.2.1]hept-5-yl]hept-5-enoic acid
-
ONO1349
(5Z)-7-[(1S,4S,5S,6R)-2-methyl-6-[(1E)-oct-1-en-1-yl]-2-azabicyclo[2.2.1]hept-5-yl]hept-5-enoic acid
-
ONO1373
(Z)-7-[(1R,4S,5S,6R)-((E)-6-oct-1-enyl)-2-aza-bicyclo[2.2.1]hept-5-yl]-hept-5-enoic acid
-
inhibition of PGH2 9,11-endoperoxide reductase activity, slight inhibition of prostamide D2 11-ketoreductase and PGD2 11-ketoreductase activity
(Z)-7-[(1R,4S,5S,6R)-2-methyl-6-((E)-oct-1-enyl)-2-aza-bicyclo[2.2.1]hept-5-yl]-hept-5-enoic acid
-
inhibition of PGH2 9,11-endoperoxide reductase activity, slight inhibition of prostamide D2 11-ketoreductase and PGD2 11-ketoreductase activity, competitive, binds to the active site
(Z)-7-[(1R,4S,5S,6R)-6-((E)-(S)-3-hydroxy-oct-1-enyl)-2-aza-bicyclo[2.2.1]hept-5-yl]-hept-5-enoic acid
-
inhibition of PGH2 9,11-endoperoxide reductase activity, slight inhibition of prostamide D2 11-ketoreductase and PGD2 11-ketoreductase activity
1-(4-aminobenzyl)-5-methoxy-2-methylindoleacetic acid
-
-
15-deoxy-DELTA12,14-prostaglandin J2
-
15d-PGJ2, the enzyme inhibitor attenuates proliferation, inhibits collagen gel contraction and induces activation of the apoptotic marker, caspase-3, in CRL1762 keloid fibroblasts
2-(1-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl)-N-((trifluoromethyl)sulfonyl)acetamide
257fold selectivity for isoform AKR1C3 over isoform AKR1C2
3-(1-(4-chlorobenzoyl)-3-ethyl-5-methoxy-1H-indol-2-yl)-propanoic acid
540fold selectivity for isoform AKR1C3 over isoform AKR1C2
3-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-propanoic acid
257fold selectivity for isoform AKR1C3 over isoform AKR1C2
4-benzoyl-benzoic acid
-
;
4-carboxy-2',4'-dinitrodiphenylamine
-
;
4-carboxy-2-aminodiphenylamine
-
;
4-chloro-N-(4-tolyl)-anthranilic acid
-
;
4-chloro-N-phenylanthranilic acid
-
;
4-nitro-N-phenylanthranilic acid
-
;
5-methyl-N-phenylanthranilic acid
-
;
9,10-phenanthrenequinone
acetate
-
occupies the oxyanion hole of the active site, 2 complex structures
aspirin
-
;
bimatoprost
FeCl2
-
-
Flufenamic acid
-
nonsteroidal anti-inflammatory drug, binds to both the active site and the beta-hairpin loop at the opposite end of the central beta-barrel, complex structure
flurbiprofen
Ibuprofen
indomethacin
indomethacin methyl ester
-
specific inhibition of isoform AKR1C3 versus AKR1C1 and AKR1C3
Meclofenamic acid
Mefenamic acid
-
;
methylglyoxal
-
-
N-(4-chlorobenzoyl)-melatonin
naproxen
ONO1349
-
-
ONO1370
-
-
ONO1373
-
-
ponalrestat
-
specific inhibitor developed to block AKR1B1 activity. Application reduces prostaglandin F2alpha production in response to interleukin IL-1beta in both cultured endometrial cells and endometrial explants
rutin
-
binding structure at the substrate binding site
salicylic acid
-
;
sorbinil
-
;
sulindac
tert-butyl hydroperoxide
-
-
Tolrestat
Zomepirac
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
interleukin-1beta
-
membrane-associated, not soluble, isozyme in WI-38 cells
-
additional information
-
PGF synthase I activity in HEK 293 cells is unaffected by interleukin-1beta
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.134
(5Z,13E)-(15S)-9alpha,11beta,15-trihydroxyprosta-5,13-dienoate
-
-
0.0774
4-nitrobenzaldehyde
-
-
0.0031
5beta-androstan-3,17-dione
-
-
0.001
5beta-Androstan-3alpha-ol-17-one
-
-
0.0008 - 0.0015
9,10-phenanthrenequinone
0.0066
androst-4-ene-3,17-dione
-
pH 7.0, 37C
0.0057
NADPH
-
-
0.0034
Prostaglandin D2
-
-
0.0019 - 0.029
prostaglandin H2
additional information
additional information
-
kinetics of 3alpha-hydroxysteroid dehydrogenase type II activity
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.4
9,10-phenanthrenequinone
-
pH 7.0, 37C
0.0027
androst-4-ene-3,17-dione
-
pH 7.0, 37C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0019
4-benzoyl-benzoic acid
-
;
0.00038
4-carboxy-2',4'-dinitrodiphenylamine
-
;
0.01
4-carboxy-2-aminodiphenylamine
-
;
0.0014
4-chloro-N-(4-tolyl)-anthranilic acid
-
;
0.0029
4-chloro-N-phenylanthranilic acid
-
;
0.0019
4-nitro-N-phenylanthranilic acid
-
;
0.0073
5-methyl-N-phenylanthranilic acid
-
;
0.0003
Mefenamic acid
-
;
0.0034
N-(4-chlorobenzoyl)-melatonin
-
-
0.0217
sorbinil
-
-
0.0036
Tolrestat
-
-
additional information
additional information
-
Ki values for the nonsteroidal anti-inflammatory drug inhibitors with 3alpha-androstanediol as a substrate
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.005 - 0.06
(5Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(1E,3S)-3-hydroxy-5-phenylpent-1-en-1-yl]cyclopentyl]-N-ethylhept-5-enamide
0.3 - 1
(5Z)-7-[(1R,4S,5S,6R)-6-[(1E)-oct-1-en-1-yl]-2-azabicyclo[2.2.1]hept-5-yl]hept-5-enoic acid
0.13 - 1
(5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-2-azabicyclo[2.2.1]hept-5-yl]hept-5-enoic acid
0.06 - 1
(5Z)-7-[(1S,4S,5S,6R)-2-methyl-6-[(1E)-oct-1-en-1-yl]-2-azabicyclo[2.2.1]hept-5-yl]hept-5-enoic acid
0.052
1-(4-aminobenzyl)-5-methoxy-2-methylindoleacetic acid
Homo sapiens;
-
pH 7.0, 37C
0.00021
2-(1-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl )-N-((trifluoromethyl)sulfonyl)acetamide
Homo sapiens;
P42330
pH not specified in the publication, temperature not specified in the publication
0.00009
3-(1-(4-chlorobenzoyl)-3-ethyl-5-methoxy-1H-indol-2-yl)-propanoic acid
Homo sapiens;
P42330
pH not specified in the publication, temperature not specified in the publication
0.00022
3-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-propanoic acid
Homo sapiens;
P42330
pH not specified in the publication, temperature not specified in the publication
0.002
4-benzoyl-benzoic acid
Homo sapiens;
-
;
0.0004
4-carboxy-2',4'-dinitrodiphenylamine
Homo sapiens;
-
;
0.011
4-carboxy-2-aminodiphenylamine
Homo sapiens;
-
;
0.0015
4-chloro-N-(4-tolyl)-anthranilic acid
Homo sapiens;
-
;
0.003
4-chloro-N-phenylanthranilic acid
Homo sapiens;
-
;
0.002
4-nitro-N-phenylanthranilic acid
Homo sapiens;
-
;
0.011
5-methyl-N-phenylanthranilic acid
Homo sapiens;
-
;
1.2
aspirin
Homo sapiens;
-
;
0.005 - 0.06
bimatoprost
0.0078
flurbiprofen
0.0099
Ibuprofen
0.0023
indomethacin
0.0023
indomethacin methyl ester
Homo sapiens;
-
pH 7.0, 37C
0.0007
Meclofenamic acid
0.00039
Mefenamic acid
Homo sapiens;
-
;
0.0078
N-(4-chlorobenzoyl)-melatonin
Homo sapiens;
-
pH 7.0, 37C
0.0014
naproxen
0.13 - 1
ONO1349
0.3 - 1
ONO1370
0.06 - 1
ONO1373
0.77
salicylic acid
Homo sapiens;
-
;
0.0034
sulindac
0.1 - 0.45
Tolrestat
0.04
Zomepirac
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.078
-
purified recombinant enzyme, pH 7.0, 25C, in presence of 0.05 mM 9,10-phenanthrenequinone
0.2
-
about, purified recombinant enzyme, pH 7.0, 25C
2.4
-
pH 5.5, 37C
additional information
-
at 37C in 100 mM Tris/HCl (pH 7.0), the reaction product, 9-alpha,11-beta-prostaglandin F2 is detected as well as the substrate prostaglandin D2 in the reaction solution after reaction for 1 h, the amount of the product increases linearly for 1 h and then gradually plateaues
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8
-
assay at
8 - 9
-
reduction of prostaglandin D2
9 - 10
-
oxidation of 9alpha,11beta-prostaglandin F2
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
24
-
assay at
25
-
assay at
30
-
assay at, PGH2 9,11-endoperoxide reductase activity
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25 - 37
-
the activity increases gradually as the temperature increases from 25 to 37C, and then decreases significantly at 45C compared with that at 37C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
expression of genes for PGE2 synthesis, with low levels of prostaglandin transporters and dehydrogenase
Manually annotated by BRENDA team
-
normal breast expresses very high levels of AKR1C3 relative to other tissues
Manually annotated by BRENDA team
-
production of PGE2, PGF2 and PGD2 and high prostaglandin turnover
Manually annotated by BRENDA team
-
keloid fibroblasts
Manually annotated by BRENDA team
-
isoform AKR1B1 is expressed at a high level during the menstrual cycle during the secretory phase and in both epithelial and stromal cells
Manually annotated by BRENDA team
-
isoform AKR1B1 is expressed at a high level during the menstrual cycle during the secretory phase and in both epithelial and stromal cells
Manually annotated by BRENDA team
-
glioblastoma cell
Manually annotated by BRENDA team
both activities of enzymes AKR1C1/AKR1C2 and AKR1C3 are present in the periovuatory granulosa cell
Manually annotated by BRENDA team
-
embryonic kidney cell, isozyme PGFS-I
Manually annotated by BRENDA team
-
proximal tubule, the enzyme is associated with the cyclooxygenase-I, COX-I
Manually annotated by BRENDA team
-
high expression level
Manually annotated by BRENDA team
-
in pregnant myometrium, PGI2, PGD2 and PGF2 synthases are highly expressed while prostaglandin dehydrogenase is underexpressed. Myometrium from non-pregnant women has lower levels of prostaglandin synthases and higher levels of prostaglandin dehydrogenase than pregnant myometrium
Manually annotated by BRENDA team
-
the enzyme is associated with the cyclooxygenase-II, COX-II
Manually annotated by BRENDA team
-
AKR1C3 is overexpressed in skin squamous cell carcinoma (SCC) and affects SCC growth via prostaglandin metabolism
Manually annotated by BRENDA team
-
high expression level
Manually annotated by BRENDA team
-
glioblastoma cell
Manually annotated by BRENDA team
-
lung fibroblast cell
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
inducible isozyme m-PGFS
Manually annotated by BRENDA team
PDB
SCOP
CATH
UNIPROT
ORGANISM
Homo sapiens;
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
35000
-
x * 35000, SDS-PAGE; x * 35000, SDS-PAGE
36840
-
amino acid analysis
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
enzyme has a (alpha/beta)8 barrel structure, from crystal structure determination
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
16 mg/ml purified enzyme complexed with inhibitors acetate, flufenamic acid or indomethacin, hanging drop vapour diffusion method in 0.006 ml drops, 1:1 mixture of protein solution containing 10 mM potassium phosphate, pH 7.0, 1 mM DTT, 1 mM EDTA, 2 mM NADP+, with reservoir solution containing 25% w/v PEG 4000, 100 mM sodium citrate, pH 6.0, 2.5% v/v 2-methyl-2,4-pentanediol, and 800 mM ammonium acetate, 6 days to maximum size, X-ray diffraction structure determination of the complexes and analysis at 1.2-2.1 A resolution
-
20 mg/ml purified recombinant enzyme in a solution containing 1.4 mM PGD2 or inhibitor rutin, 1.2 mM NADP+ and NADPH, 50 mM MES, pH 6.0, and 25% w/v PEG 8000, hanging drop vapour diffusion method, 2-3 days, thick plate-shaped crystals of enzyme with NADP+ and PGD2 and of enzyme with NADPH and rutin, X-ray diffraction structure determination and analysis at 1.69 A resolution
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AKR1C3 in complex with NADP+ and indomethacin
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homology modeling of enzyme in complex with inhibitor indomethacin
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in complex with bimatoprost and NADPH, hanging drop vapor diffusion method, using 1.0 mM BMP, 1.0 mM NADPH, 0.14 M NaCl, 50 mM MES buffer (pH 7.0), and 26% (w/v) PEG 8000; purified recombinant enzyme in complex with NADPH and bimatoprost BMP, an ocular hypotensive agent bound near the PGD2 binding site located on the alpha- and omega-chains, hanging drop vapour diffusion method, from 50 mM MES, pH 7.0, containing 7 mg/ml protein, 0.14 M NaCl, 26% w/v PEG 8000, 1.0 mM NADPH, and 1.0 mM BMP, added in a 95% ethanol solution, 4C, 14 days, thick plate-shaped crystals, X-ray diffraction structure determination and analysis at 2.0 A resolution
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
; recombinant enzyme from Escherichia coli strain HB101 to homogeneity
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; recombinant enzyme from Escherichia coli, to homogeneity
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recombinant enzyme from Escherichia coli to homogeneity
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to apparent homogeneity, on Ni-NTA resin and by gel filtration; to apparent homogeneity, on Ni-NTA resin and by gel filtration
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli HB101 cells; expression Escherichia coli HB101
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expressed in Escherichia coli HB101 cells; expression in Escherichia coli strain HB101
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expression in Escherichia coli
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expression in Escherichia coli BL21(DE3)
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expression in Escherichia coli HB101
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gene AKR1B1, cloning from genomic DNA, DNA and amino acid sequence determination and analysis, recombinant expression in immortalized human endometrial stromal cells, HIESC-2 cells, expression analysis in clones 16-1, 16-2, and 16-4. Clones 16-1 and 16-2 present with a complete absence of AKR1B1 protein, while clone 16-4 is able to express the AKR1B1 protein. Following treatment of cells with interleukin-1beta, both wild-type and clone 16-4 cells exhibit a similar response, but clone 16-2 does not respond with increased production of eitherPGF2alpha or PGE2. At the protein level, IL-1beta induces an increase in mPGES-1 and COX-2 protein expression but in clone 16-2 the relative increase of Cox-2 protein is weaker
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gene AKR1C3, expression analysis
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gene AKR1C3, recombinant expression of N-terminally His8-tagged enzyme in Escherichia coli strain BL21(DE3)pLysS
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into vector pET-28a and expressed in Escherichia coli BL21 (DE3); into vector pET-28a and expressed in Escherichia coli BL21 (DE3)
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overexpression of AKR1C3 using a pLNCX retroviral vector in MCF-7 cell line
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recombinant enzyme is expressed in Escherichia coli
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SCC cell line is infected with either AKR1C3 overexpressing retroviral construct (SCC-AKR1C3), quantitative AKR1C3 expression analysis in wild-type and mtransfected cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
AKR1B1 shows decreased expression in neoplastic disease, AKR1B1 activity might be suppressed in tumor cells in breast cancer tissues
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AKR1C3 expression is induced by interleukin-1beta leading to a higher production of prostaglandin F2alpha
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AKR1C3 is overexpressed in skin squamous cell carcinoma (SCC) and affects SCC growth via prostaglandin metabolism. It is upregulated by its substrate, prostaglandin D2
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expression of AKR1B1 is upregulated in the fetal membranes in association with term labor, during labor tumor necrosis factor TNF upregulates the AKR1B1 protein expression
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in cultured myometrial cells there is a dose-dependent stimulatory effect of interleukin 1beta and tumor necrosis factor alpha on PTGS2, PTGES and AKR1B1, i.e.PGF synthase expression
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interleukin IL-1beta is able to upregulate COX-2 and AKR1B1 proteins as well as prostaglandin F2alpha production under normal glucose concentrations. The promoter activity of AKR1B1 gene is increased by IL-1beta particularly around the multiple stress response region
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D43E
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only trace activities in presence and absence of NADPH
D43N
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only trace activities in presence and absence of NADPH
H110A
-
only trace activities in presence and absence of NADPH
H110F
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only trace activities in presence and absence of NADPH
K77L
-
only trace activities in presence and absence of NADPH
K77R
-
only trace activities in presence and absence of NADPH
Y48F
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69% of wild-type activity in presence of NADPH, 138% of wild-type isomerization activity in absence of NADPH, 0.2% of wild-type activity reducing 4-nitrobenzaldehyde
Y55F
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site-directed mutagenesis, the mutant loses its PGD2 11-ketoreductase activity, but not the PGH2 9,11-endoperoxide reductase; the mutated enzyme loses the prostaglandin D2 11-ketoreductase activity but retains the prostaglandin H2 9,-11-endoperoxide reductase activity
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
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prostaglandin formation is a key component of PGaction and the specific target of non-steroidal anti-inflammatory drugs
medicine
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AKR1C3 likely plays important roles in the development of hormone-dependent, and possibly hormone-independent, breast cancer. It is highly expressed in normal breast and upregulated in breast cancer, where its expression is associated with a worse prognosis
molecular biology
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genome editing of human cell lines can be used to complement mouse KO models to validate the function of genes in differentiated tissues and cells
pharmacology
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enzyme is a target for cyclooxygenase-independent antineoplastic actions of nonsteroidal anti-inflammatory drugs
synthesis
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development of a coupled assay method for enzymatic formation of prostamide F2alpha from anandamide by the cyclooxygenase-II and the prostaglandin synthase F involving the intermediate metabolite, prostamide H2