Information on EC 1.3.1.48 - 13,14-dehydro-15-oxoprostaglandin 13-reductase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
1.3.1.48
-
RECOMMENDED NAME
GeneOntology No.
13,14-dehydro-15-oxoprostaglandin 13-reductase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
11alpha-hydroxy-9,15-dioxoprostanoate + NAD(P)+ = (13E)-11alpha-hydroxy-9,15-dioxoprost-13-enoate + NAD(P)H + H+
show the reaction diagram
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
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redox reaction
reduction
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-
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SYSTEMATIC NAME
IUBMB Comments
11alpha-hydroxy-9,15-dioxoprostanoate:NAD(P)+ Delta13-oxidoreductase
Reduces 13,14-dehydro-15-oxoprostaglandins to 13,14-dihydro derivatives. The enzyme from placenta is specific for NAD+.
CAS REGISTRY NUMBER
COMMENTARY hide
57406-74-3
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
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Manually annotated by BRENDA team
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Uniprot
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(5S,12R)-dihydroxy-(6E,8Z,10Z,14E)-eicosatetraenoic acid + NADH
?
show the reaction diagram
(5S,6R)-dihydroxy-15-oxo-(7E,9E,11Z,13E)-eicosatetraenoic acid + NADH
13,14-dihydro-(5S,6R)-dihydroxy-15-oxo-(7E,9E,11Z)-eicosatetraenoic acid + NAD+
show the reaction diagram
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trivial name 15-oxo-lipoxin A4
-
?
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NAD(P)H
(5Z)-11alpha-hydroxy-9,15-dioxoprost-5-enoate + NAD(P)+
show the reaction diagram
(Z)-3-[(5-methoxy-3-oxo-2(3H)-benzofuranylidene)-methyl]benzoic acid + NAD(P)H
[(5-methoxy-3-oxo-benzofurane)-methyl]benzoic acid + NAD(P)+
show the reaction diagram
-
-
-
?
1-(p-carboxyphenyl)-5-cyano-3-oxo-1-pentene + NAD(P)H
1-(p-carboxyphenyl)-5-cyano-3-oxo-pentane + NAD(P)+
show the reaction diagram
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-
-
?
11-hydroxy-9,15-dioxoprosta-5,13-dien-1-oic acid + NAD(P)H
11-hydroxy-9,15-dioxoprosta-5-en-1-oic acid + NAD(P)+
show the reaction diagram
11-hydroxy-9,15-dioxoprosta-5,13-dien-1-oic acid + NADPH
11-hydroxy-9,15-dioxoprosta-5-en-1-oic acid + NADP+
show the reaction diagram
-
-
-
-
?
15-ketoprostaglandin A1 + NAD(P)H
?
show the reaction diagram
15-ketoprostaglandin B1 + NAD(P)H
?
show the reaction diagram
15-ketoprostaglandin E + NAD(P)H
?
show the reaction diagram
15-ketoprostaglandin E1 + NADPH
?
show the reaction diagram
15-ketoprostaglandin E2 + NADPH
13,14-dihydro-15-keto-prostaglandin E2 + NADP+
show the reaction diagram
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-
-
?
15-ketoprostaglandin E2 + NADPH
?
show the reaction diagram
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-
-
-
?
15-ketoprostaglandin F1alpha + NAD(P)H
?
show the reaction diagram
15-ketoprostaglandin F1alpha + NADPH
?
show the reaction diagram
-
-
-
?
15-ketoprostaglandin F2alpha + NADPH
?
show the reaction diagram
15-oxoprostaglandin F1alpha + NAD(P)H
?
show the reaction diagram
3-nonen-2-one + NADPH
nonane-2-one + NADP+
show the reaction diagram
-
-
-
?
3-penten-2-one + NADPH
pentane-2-one + NADP+
show the reaction diagram
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-
-
?
4-hydroxy-2-hexenal + NADPH
4-hydroxyhexanal + NADP+
show the reaction diagram
-
-
-
?
4-hydroxy-2-nonenal + NADPH
4-hydroxynonanal + NADP+
show the reaction diagram
-
-
-
?
4-hydroxy-2-nonenal + NADPH
?
show the reaction diagram
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-
-
-
?
6,15-diketo-prostaglandin F1alpha + NAD(P)H
?
show the reaction diagram
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-
-
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?
9,11-dihydroxy-15-oxoprosta-5,13-dien-1-oic acid + NAD(P)H
9,11-dihydroxy-15-oxoprosta-5-en-1-oic aicd + NAD(P)+
show the reaction diagram
acrolein + NADPH
propanal + NADP+
show the reaction diagram
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-
-
?
alpha-methylcinnamaldehyde + NADPH
?
show the reaction diagram
-
-
-
-
?
benzylidene acetone + NADPH
?
show the reaction diagram
-
-
-
-
?
benzylidene acetonphenone + NADPH
?
show the reaction diagram
-
-
-
-
?
beta-ionone + NAD(P)H
?
show the reaction diagram
-
-
-
-
?
chalcone + NADPH
?
show the reaction diagram
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-
-
-
?
cinnamaldehyde + NADPH
?
show the reaction diagram
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-
-
-
?
cinnamoylthiophene + NADPH
?
show the reaction diagram
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-
-
-
?
curcumin + NAD(P)H
?
show the reaction diagram
-
-
-
-
?
ethylvinylketone + NADPH
pentane-3-one + NADP+
show the reaction diagram
-
-
-
?
leukotriene B4 + NADPH
?
show the reaction diagram
methyl vinyl ketone + NADPH
?
show the reaction diagram
-
-
-
-
?
phenyl propenyl ketone + NADPH
?
show the reaction diagram
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-
-
-
?
trans-2-(o-hydroxybenzylidene)acetophenone + NAD(P)H
(o-hydroxybenzyl)acetophenone + NAD(P)+
show the reaction diagram
-
-
-
?
trans-2-benzylidenecyclohexan-2-one + NAD(P)H
benzylcyclohexan-2-one + NAD(P)+
show the reaction diagram
-
-
-
?
trans-2-butenal + NAD(P)H
butanal + NAD(P)+
show the reaction diagram
trans-2-decenal + NADPH
decanal + NADP+
show the reaction diagram
-
-
-
?
trans-2-dodecenal + NADPH
dodecanal + NADP+
show the reaction diagram
-
-
-
?
trans-2-hexenal + NAD(P)H
hexanal + NAD(P)+
show the reaction diagram
trans-2-hexenal + NADPH
?
show the reaction diagram
-
-
-
-
?
trans-2-nonenal + NADPH
nonanal + NADP+
show the reaction diagram
-
-
-
?
trans-2-octenal + NADPH
octanal + NADP+
show the reaction diagram
-
-
-
?
trans-2-pentenal + NADPH
pentanal + NADP+
show the reaction diagram
-
-
-
?
trans-3-(2-furyl)acrolein + NAD(P)H
2-furylpropanal + NAD(P)+
show the reaction diagram
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-
-
?
trans-4-furyl-3-buten-2-one + NAD(P)H
4-furyl-butane-2-one + NAD(P)+
show the reaction diagram
-
-
-
?
trans-benzylideneacetone + NAD(P)H
benzylacetone + NAD(P)+
show the reaction diagram
trans-benzylideneacetophenone + NAD(P)H
benzylacetophenone + NAD(P)+
show the reaction diagram
-
-
-
?
trans-cinnamaldehyde + NAD(P)H
?
show the reaction diagram
trans-cinnamic acid ethyl ester + NAD(P)H
?
show the reaction diagram
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-
-
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?
trans-cinnamoyl thiophene + NAD(P)H
?
show the reaction diagram
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-
-
-
?
trans-methylvinylketone + NAD(P)H
butane-2-one + NAD(P)+
show the reaction diagram
trans-phenyl-1-propenyl ketone + NAD(P)H
phenylpropane-1-one + NAD+
show the reaction diagram
-
-
-
?
trans-trans-2,4-hexadienal + NAD(P)H
?
show the reaction diagram
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
15-ketoprostaglandin E + NAD(P)H
?
show the reaction diagram
15-oxoprostaglandin F1alpha + NAD(P)H
?
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NAD(P)H
NADPH
nicotinamide hypoxanthine dinucleotide
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-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
13,14-Dihydro-15-prostaglandin E2
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competitive product inhibition
15-keto prostaglandin F2alpha
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43.06% residual activity at 0.1 mM
benzylidene acetophenone
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21.09% residual activity at 0.5 mM
Cibacron blue 3 G-A
dicoumarol
Disulfiram
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0.1 mM, 61% inhibition, cofactor NADPH, substrate 15-ketoprostaglandin E2
indomethacin
NADH
-
uncompetitive inhibition at high concentrations
NADPH
p-chloromercuribenzoate
quercitrin
additional information
-
finasteride has no inhibitory effect
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.093
(5S,12R)-dihydroxy-(6E,8Z,10Z,14E)-eicosatetraenoic acid
-
-
0.0085
15-Keto-prostaglandin E2
-
-
0.0075
15-Ketoprostaglandin A1
-
-
0.0112
15-Ketoprostaglandin B1
-
-
0.0039 - 0.0344
15-ketoprostaglandin E1
0.0078 - 0.07
15-Ketoprostaglandin E2
0.0592 - 0.184
15-ketoprostaglandin F1alpha
0.000213 - 0.1088
15-ketoprostaglandin F2alpha
0.001
15-oxoprostaglandin E1
-
-
0.016
3-nonen-2-one
-
-
0.49
3-penten-2-one
-
-
0.21
4-hydroxy-2-hexenal
-
-
0.12 - 0.461
4-hydroxy-2-nonenal
0.258
6,15-diketo-prostaglandin F1alpha
-
-
0.15
acrolein
-
-
1.7
alpha-methylcinnamaldehyde
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-
0.0277 - 0.039
benzylidene acetone
0.1399
benzylidene acetonphenone
-
in 100 mM phosphate buffer (pH 7.4), at 25°C
0.18
chalcone
-
-
0.075 - 1.426
cinnamaldehyde
0.0791
cinnamoylthiophene
-
in 100 mM phosphate buffer (pH 7.4), at 25°C
3.9
crotonaldehyde
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-
0.11
ethylvinylketone
-
-
0.063
hypoxanthine dinucleotide
-
-
-
0.01
leukotriene B4
-
recombinant enzyme
0.1289
Methyl vinyl ketone
-
in 100 mM phosphate buffer (pH 7.4), at 25°C
0.58
methylvinylketone
-
-
0.032 - 0.16
NADH
0.005 - 0.0946
NADPH
0.0123
phenyl propenyl ketone
-
in 100 mM phosphate buffer (pH 7.4), at 25°C
0.41
trans,trans-2,4-nonadienal
-
-
0.04
trans-2-decenal
-
-
0.06
trans-2-dodecenal
-
-
1 - 2.194
trans-2-hexenal
0.046
trans-2-nonenal
-
-
0.36
trans-2-octenal
-
-
2.4
trans-2-pentenal
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.7 - 1
15-ketoprostaglandin E
Bos taurus
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-
0.12 - 1.52
15-ketoprostaglandin E1
0.19
15-Ketoprostaglandin E2
Mus musculus
Q8VDQ1
in 0.1 M Tris-HCl (pH 7.4), at 37°C
0.22
15-ketoprostaglandin F1alpha
Mus musculus
Q8VDQ1
in 0.1 M Tris-HCl (pH 7.4), at 37°C
0.25
15-ketoprostaglandin F2alpha
Mus musculus
Q8VDQ1
in 0.1 M Tris-HCl (pH 7.4), at 37°C
40
15-oxoprostaglandin E1
Rattus norvegicus
-
-
19.8
3-nonen-2-one
Rattus norvegicus
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-
18.5
3-penten-2-one
Rattus norvegicus
-
-
13.4
4-hydroxy-2-hexenal
Rattus norvegicus
-
-
67.3
4-hydroxy-2-nonenal
Rattus norvegicus
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-
3.72
acrolein
Rattus norvegicus
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13.1
alpha-methylcinnamaldehyde
Rattus norvegicus
-
-
54.7
benzylidene acetone
Rattus norvegicus
-
-
32.3
chalcone
Rattus norvegicus
-
-
15.7
cinnamaldehyde
Rattus norvegicus
-
-
8.05
crotonaldehyde
Rattus norvegicus
-
-
160
ethylvinylketone
Rattus norvegicus
-
-
156
methylvinylketone
Rattus norvegicus
-
-
0.16
NADPH
Mus musculus
Q8VDQ1
in 0.1 M Tris-HCl (pH 7.4), at 37°C
17.2
trans,trans-2,4-nonadienal
Rattus norvegicus
-
-
70.8
trans-2-decenal
Rattus norvegicus
-
-
60.2
trans-2-dodecenal
Rattus norvegicus
-
-
28.8
trans-2-hexenal
Rattus norvegicus
-
-
94.5
trans-2-nonenal
Rattus norvegicus
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-
89.7
trans-2-octenal
Rattus norvegicus
-
-
16.8
trans-2-pentenal
Rattus norvegicus
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.079
13,14-Dihydro-15-prostaglandin E2
-
-
0.0000125
Cibacron Blue 3G-A
-
-
0.00001
NADPH
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00026
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enzyme activity in cornea, substrate 15-ketoprostaglandin, cofactor NADPH
0.000389
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enzyme activity in retina, substrate 15-ketoprostaglandin, cofactor NADPH
0.00085
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enzyme activity in retinal pigment epithelium, substrate 15-ketoprostaglandin, cofactor NADPH
0.000945
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enzyme purified from iris-ciliary cytosol
0.0012
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enzyme activity in ciliary body, substrate 15-ketoprostaglandin, cofactor NADPH
0.00145
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enzyme activity in iris, substrate 15-ketoprostaglandin, cofactor NADPH
0.0405
-
-
0.115
using 15-ketoprostaglandin E1 as a substrate, at 37°C
0.1784
using 15-ketoprostaglandin E2 as a substrate, at 37°C
0.2064
using 15-ketoprostaglandin F1alpha as a substrate, at 37°C
0.2309
using 15-ketoprostaglandin F2alpha as a substrate, at 37°C
0.393
-
-
0.425
-
-
2.56
-
-
2.6
-
recombinant enzyme expressed in Escherichia coli
additional information
after restoration of LTBDH/PGR expression in LTBDH/PGR-negative (H1299) or -low (A549) lung cancer cell lines, the restored enzyme induces apoptosis and growth inhibition in vitro, restoration of LTBDH/PGR expression is effective in preventing lung cancer growth in vitro and in vivo; cell cycle alterations induced by LTBDH/PGR over-expression are assessed with Ad-GFP or Ad-PGR after infection at 100 MOI for 72 h, after infection with Ad-PGR, the apoptosis population in A549 cells and H1299 cells is 8.59% and 9.57%, whereas apoptosis population is not detected significantly in H157 infected cells; effects of induced expression of LTBDH/PGR in H1299 cells, LTBDH/PGR expression increases in a dose and time dependent manner after tetracycline treatment, marked expression is observed at day 4 and significantly affects cell proliferation beginning day 5 causing reduction in cell number and suggesting that LTBDH/PGR expression inhibit growth of H1299 cells; the expression of apoptosis-related proteins BAX, Bcl-2 and CD44 in H1299 and H157 cells is not changed by LTBDH/PGR over-expression except for BAX which is decreased in H157 cells, endogenous p53 and p21 are not expressed in both H1299 and H157 cells
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 7.5
-
spontaneous oxidation of NADH below pH 6.0
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
-
assay at
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
35000
-
2 * 35000, SDS-PAGE
39500
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1 * 39500, SDS-PAGE
42000
-
gel filtration
55000
-
gel filtration
56000
-
gel filtration
57000
-
1 * 57000, SDS-PAGE
68500
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
-
2 * 35000, SDS-PAGE
monomer
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystal structure of the bifunctional leukotriene B4 12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase, the binary complex structure with NADP+, and the ternary complex structure with NADP+ and 15-oxo-prostaglandin E2, batch method using the automated crystallization system TERA by mixing equal volumes of protein solution (20 mM Tris-HCL, pH 8.0, 150 mM NaCl, 1 mM dithiothreitol) and precipitating solution (100 mM 4-morpholineethanesulfonic acid, pH 5.5-6.8), 17.5-27.5% polyethylene glycol 4000, 50 mM MgCl2 at 18°C
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leukotriene B4 12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase complex in ternary complex with indomethacin and NADP+. Indomethacin binds in anti-configuration at one of the active side clefts of the homodimer interface of the enzyme. The chlorobenzene is buried in the hydrophobic pore and the carboxyl group interacts with the guanidino group of R56 and the phenolic hydroxyl group of Y262
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 50% glycerol v/v, 5 mM potassium phosphate, 1 mM EDTA, pH 7.0, stable for at least 6 months
-
-4°C, 0.1 M sodium phosphate, pH 7.4, 1 mM EDTA, 1 mM mercaptoethanol, stable for more than 1 month
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-80°C, NADH-linked activity is lost overnight
-
-80°C, stable for more than 1 year
-
0°C, NADPH-linked activity is lost after a few hours
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4°C, stable for several weeks in absence of glycerol
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2',5'-ADP Sepharose 4B column chromatography and HisTrap HP column chromatography
-
DEAE-cellulose, phenyl-toyopearl, blue-toyopearl, hydroxyapatite, liver enzyme
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glutathione-Sepharose column chromatography
native and recombinant enzyme
-
recombinant enzyme
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
effects of LTBDH/PGR expression in LTBDH/PGR-negative and -positive lung cancer cells by infection with adenovirus carrying the LTBDH/PGR gene and by stable transfection with an inducible LTBDH/PGR expression vector; expressed in H1299, A549, H157 and AD-293 cells applying an adenoviral shuttle vector
expressed in Escherichia coli strain XL1-Blue
expressed in Escherichia coli Top10 cells
-
expression in Escherichia coli
expression in Escherichia coli as glutathione-S-transferase fusion protein
-