Information on EC 1.1.1.141 - 15-hydroxyprostaglandin dehydrogenase (NAD+)

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The expected taxonomic range for this enzyme is: Amniota

EC NUMBER
COMMENTARY
1.1.1.141
-
RECOMMENDED NAME
GeneOntology No.
15-hydroxyprostaglandin dehydrogenase (NAD+)
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
(5Z,13E,15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+ = (5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
NAD+ is added first, followed by prostaglandin E2, 15-ketoprostaglandin is released followed by NADH
-
(5Z,13E,15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+ = (5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
single displacement mechanism
-
(5Z,13E,15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+ = (5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
ordered bi-bi-mechanism
-
(5Z,13E,15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+ = (5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
ordered bi-bi-mechanism
-
(5Z,13E,15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+ = (5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
displacement reaction mechanism, at pH 7.0 a kinetically significant ternary complex is formed, while at pH 9.0 the ternary complex is not kinetically significant, Theorell-Chance mechanism
-
(5Z,13E,15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+ = (5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
residues and domains involved in catalysis and substrate binding, overview
-
(5Z,13E,15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+ = (5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
substrate binidng and catalytic mechanism of the enzyme, homology modeling, docking and molecular dynamics simulation, residues Gln148, Ser138, Tyr151, and Lys155 are important, overview
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
(5Z,13E,15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate:NAD+ 15-oxidoreductase
Acts on prostaglandin E2, F2alpha and B1, but not on prostaglandin D2. cf. EC 1.1.1.196 15-hydroxyprostaglandin-D dehydrogenase (NADP+) and EC 1.1.1.197 15-hydroxyprostaglandin dehydrogenase (NADP+).
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
11alpha,15-dihydroxy-9-oxoprost-13-enoate:NAD+ 15-oxidoreductase
-
-
-
-
15-hydroxy prostaglandin dehydrogenase
-
-
15-hydroxyprostaglandin dehydrogenase
Q309F3
-
15-hydroxyprostaglandin dehydrogenase
-
-
15-hydroxyprostaglandin dehydrogenase
-
-
15-hydroxyprostaglandin dehydrogenase
Mus musculus C57BL/6J
-
-
-
15-hydroxyprostaglandin dehydrogenase
-
-
15-hydroxyprostaglandin dehydrogenase
-
-
15-hydroxyprostaglandin dehydrogenase
-
-
15-hydroxyprostaglandin-dehydrogenase
-
-
15-hydroxyprostanoic dehydrogenase
-
-
-
-
15-OH-PGDH
-
-
-
-
15-PGDH
Q309F3
-
15-PGDH
P15428
-
15-PGDH
-
-
15-prostaglandin dehydrogenase
P15428
-
dehydrogenase, 15-hydroxyprostaglandin
-
-
-
-
HPGD
-
-
NAD+ dependent 15-hydroxyprostaglandin dehydrogenase
Q309F3
-
NAD+ dependent 15-hydroxyprostaglandin dehydrogenase
-
-
NAD+ dependent PGDH
-
-
NAD+-15-hydroxy prostanoate oxidoreductase
-
-
NAD+-dependent 15-hydroxyprostaglandin dehydrogenase
-
-
NAD+-dependent 15-hydroxyprostaglandin dehydrogenase
-
-
NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (type I)
-
-
-
-
NAD+-dependent 15-PGDH
-
-
NAD+-linked 15-hydroxyprostaglandin dehydrogenase
-
-
NAD+-linked 15-hydroxyprostaglandin dehydrogenase
-
-
NAD+-linked 15-hydroxyprostaglandin dehydrogenase
-
-
NAD-dependent 15-hydroxyprostaglandin dehydrogenase
-
-
NAD-specific 15-hydroxyprostaglandin dehydrogenase
-
-
-
-
PGDH
-
-
-
-
PGDH
-
-
PGDH
-
-
prostaglandin dehydrogenase
-
-
-
-
prostaglandin dehydrogenase
-
-
CAS REGISTRY NUMBER
COMMENTARY
9030-87-9
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
; patients with primary hypertrophic osteoarthropathy
-
-
Manually annotated by BRENDA team
enzyme expression is induced in human eryrthroleukemia cells by dexamethasone
-
-
Manually annotated by BRENDA team
gene 15-Pgdh
-
-
Manually annotated by BRENDA team
rhesus monkey, inducible isozyme
-
-
Manually annotated by BRENDA team
C57BL/6J mice
-
-
Manually annotated by BRENDA team
cyclooxygenase-2 knock-out mice
-
-
Manually annotated by BRENDA team
gene 15-Pgdh
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6J
C57BL/6J mice
-
-
Manually annotated by BRENDA team
; pregnant rabbits
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
MKN45 cells stably transfected with the 15-PGDH siRNA plasmid have a significantly increased proliferation rate. SGC7901 cells (disclosing a low expression level of 15-PGDH) stably transfected with the 15-PGDH cDNA have a significantly decreased growth rate. Increased expression of 15-PGDH suppresses clone formation of gastric cancer cells in plate and soft agar colony formation assays in vitro and suppressed tumor formation in athymic nude mice in vivo. Stable silencing of 15-PGDH in gastric cancer cells also enhances cell cycle entry in vitro
malfunction
-
overexpression of 15-PGDH inhibits HCC cell growth in vitro, whereas knockdown of 15-PGDH enhances tumor growth parameters
physiological function
-
15-PGDH has a suppressive role and that its upregulation could partly reverse the malignant growth potential of gastric cancer cells both in vitro and in vivo
physiological function
-
15-PGDH inhibits hepatocellular carcinoma growth through 15-keto-PGE2/PPARgamma-mediated activation of p21WAF1/Cip1, in a tumor xenograft model in severe combined immunodeficiency mice, inoculation of human HCC cells (Huh7) with overexpression of 15-PGDH leads to significant inhibition of tumor growth, whereas knockdown of 15-PGDH enhances tumor growth
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
-
-
-
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
-
-
-
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
-
-
-
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
-
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
-
-
-
r
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
-
-
-
-
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
-
-
-
-
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
-
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
-
-
-
-
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
-
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
-
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
Q309F3
-
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
P15428
-
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
i.e. prostaglandin E1
-
-
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
i.e. prostaglandin E1
i.e. 15-ketoprostaglandin E1
r
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
catabolism of (15S)-PGE2
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
first step in prostaglandin catabolism
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
first step in prostaglandin catabolism
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
first step in prostaglandin catabolism
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
first step in prostaglandin catabolism
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
first step in prostaglandin catabolism
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
first step in prostaglnadin catabolism
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
i.e. 15-hydroxyprostaglandin or (15S)-PGE2
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
i.e. 15-hydroxyprostaglandin or (15S)-PGE2
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
i.e. 15-hydroxyprostaglandin or (15S)-PGE2
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
i.e. 15-hydroxyprostaglandin or (15S)-PGE2
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
i.e. 15-hydroxyprostaglandin or (15S)-PGE2
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
i.e. 15-hydroxyprostaglandin or (15S)-PGE2
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
Q309F3
i.e. 15-hydroxyprostaglandin or (15S)-PGE2
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
key step in prostaglandin catabolism, enzyme activation leads to reduced cell proliferation, the enzyme is an antagonist of ibuprofen
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
key step in prostaglandin inactivation
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
PGE2 degradation
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
prostaglandin E2, PGE2, a proinflammatory bioactive lipid, promotes cancer progression by modulating proliferation, apoptosis, and angiogenesis, PGE2 is a downstream product cyclooxygenase and is biochemically inactivated by the enzyme
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
reciprocal regulation of cyclooxygenase-2 and 15-hydroxyprostaglandin dehydrogenase expression in A549 human lung adenocarcinoma cells, overview
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
the enzyme is a putative cyclooxygenase-2 antagonist and and tumor suppressor
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
transcriptional regulation and biological functions, the enzyme cooperates with cyclooxygenase-2 to control cellular prostaglandin levels, reciprocal regulation of the two enzymes, overview
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
i.e. 15-hydroxyprostaglandin or (15S)-PGE2, best substrate
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
i.e. 15-hydroxyprostaglandin or (15S)-PGE2, inactivation
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
i.e. 15-hydroxyprostaglandin or (15S)-PGE2, substrate binding structure analysis, determination of interactions
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
i.e. 15-hydroxyprostaglandin or PGE2
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
Mus musculus C57BL/6J
-
i.e. 15-hydroxyprostaglandin or (15S)-PGE2
-
-
?
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
show the reaction diagram
-
-
i.e. 15-hydroxyprostaglandin or (15S)-PGE2
-
r
(5Z,8E,10E,12S)-12-hydroxy-5,8,10-heptadecatrienoic acid + NAD+
(5Z,8E,10E)-12-oxo-5,8,10-heptadecatrienoic acid + NADH
show the reaction diagram
-
-
-
-
(5Z,8E,10E,12S)-12-hydroxy-5,8,10-heptadecatrienoic acid + NAD+
(5Z,8E,10E)-12-oxo-5,8,10-heptadecatrienoic acid + NADH
show the reaction diagram
-
-
-
?
(5Z,8E,10E,12S)-12-hydroxy-5,8,10-heptadecatrienoic acid + NAD+
(5Z,8E,10E)-12-oxo-5,8,10-heptadecatrienoic acid + NADH
show the reaction diagram
-
-
-
-
?
11alpha,15(S)-dihydroxy-9-ketoprost-5,13-dienoic acid + NAD(P)+
11alpha-hydroxy-9,15-diketoprost-5,13-dienoic acid + NADH
show the reaction diagram
-
-
-
-
11alpha,15(S)-dihydroxy-9-ketoprost-5,13-dienoic acid + NAD(P)+
11alpha-hydroxy-9,15-diketoprost-5,13-dienoic acid + NADH
show the reaction diagram
-
-
-
?
11alpha,15(S)-dihydroxy-9-ketoprost-5,13-dienoic acid + NAD(P)+
11alpha-hydroxy-9,15-diketoprost-5,13-dienoic acid + NADH
show the reaction diagram
-
-
-
?
11alpha,15(S)-dihydroxy-9-ketoprost-5,13-dienoic acid + NAD(P)+
11alpha-hydroxy-9,15-diketoprost-5,13-dienoic acid + NADH
show the reaction diagram
-
-
-
?
11alpha,15(S)-dihydroxy-9-ketoprost-5,13-dienoic acid + NAD(P)+
11alpha-hydroxy-9,15-diketoprost-5,13-dienoic acid + NADH
show the reaction diagram
-
-
-
-
11alpha,15(S)-dihydroxy-9-ketoprost-5,13-dienoic acid + NAD(P)+
11alpha-hydroxy-9,15-diketoprost-5,13-dienoic acid + NADH
show the reaction diagram
-
-
-
?
11alpha,15(S)-dihydroxy-9-ketoprost-5,13-dienoic acid + NAD(P)+
11alpha-hydroxy-9,15-diketoprost-5,13-dienoic acid + NADH
show the reaction diagram
-
-
-
?
11alpha,15(S)-dihydroxy-9-ketoprost-5,13-dienoic acid + NAD(P)+
11alpha-hydroxy-9,15-diketoprost-5,13-dienoic acid + NADH
show the reaction diagram
-
-
-
-
11alpha,15(S)-dihydroxy-9-ketoprost-5,13-dienoic acid + NAD(P)+
11alpha-hydroxy-9,15-diketoprost-5,13-dienoic acid + NADH
show the reaction diagram
-
-
-
?
11alpha,15(S)-dihydroxy-9-ketoprost-5,13-dienoic acid + NAD(P)+
11alpha-hydroxy-9,15-diketoprost-5,13-dienoic acid + NADH
show the reaction diagram
-
-
-
-
11alpha,15(S)-dihydroxy-9-ketoprost-5,13-dienoic acid + NAD(P)+
11alpha-hydroxy-9,15-diketoprost-5,13-dienoic acid + NADH
show the reaction diagram
-
-
-
?
11alpha,15(S)-dihydroxy-9-ketoprost-5,13-dienoic acid + NAD(P)+
11alpha-hydroxy-9,15-diketoprost-5,13-dienoic acid + NADH
show the reaction diagram
-
specific for NAD+
-
?
11alpha,15(S)-dihydroxy-9-ketoprost-5,13-dienoic acid + NAD(P)+
11alpha-hydroxy-9,15-diketoprost-5,13-dienoic acid + NADH
show the reaction diagram
-
specific for NAD+
-
?
11alpha,15(S)-dihydroxy-9-ketoprost-5,13-dienoic acid + NAD(P)+
11alpha-hydroxy-9,15-diketoprost-5,13-dienoic acid + NADH
show the reaction diagram
-
specific for NAD+
-
?
11alpha,15(S)-dihydroxy-9-ketoprost-5,13-dienoic acid + NAD(P)+
11alpha-hydroxy-9,15-diketoprost-5,13-dienoic acid + NADH
show the reaction diagram
-
NAD+ is much more effective than NADP+
-
?
11alpha,15(S)-dihydroxy-9-ketoprost-5,13-dienoic acid + NAD(P)+
11alpha-hydroxy-9,15-diketoprost-5,13-dienoic acid + NADH
show the reaction diagram
-
NADP+ is more effective than NAD+
-
?
15(S)-hydroperoxy-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic acid + NAD+
15-oxo-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic acid + NADH
show the reaction diagram
-
-
-
-
?
15-hydroxyeicosatetraenoic acid + NAD+
15-ketoeicosatetraenoic acid + NADH
show the reaction diagram
-
-
-
?
15-hydroxyprostaglandin + NAD+
15-oxoprostaglandin + NADH + H+
show the reaction diagram
-
-
-
-
?
15-hydroxyprostaglandin + NAD+
15-oxoprostaglandin + NADH + H+
show the reaction diagram
-
physiological inactivation of prostaglandin by catalyzing the first step in catabolism
-
-
15-hydroxyprostaglandin + NAD+
15-oxoprostaglandin + NADH + H+
show the reaction diagram
-
physiological inactivation of prostaglandin by catalyzing the first step in catabolism
-
-
15-hydroxyprostaglandin + NAD+
15-oxoprostaglandin + NADH + H+
show the reaction diagram
-
physiological inactivation of prostaglandin by catalyzing the first step in catabolism
-
-
19-hydroxyprostaglandin E1 + NAD+
19-hydroxy-15-oxoprostaglandin E1 + NADH
show the reaction diagram
-
-
-
?
20-hydroxyprostaglandin E1 + NAD+
20-hydroxy-15-ketoprostaglandin E1 + NADH
show the reaction diagram
-
-
-
?
5,6-chrysenequinone + NADH
?
show the reaction diagram
-
-
-
-
?
5,6-chrysenequinone + NADH
? + H2O2
show the reaction diagram
-
formation of potentially hazardous semiquinones, reaction mechanism, overview
-
-
?
6-keto-prostaglandin E1 + NAD+
? + NADH
show the reaction diagram
-
-
-
-
?
6-keto-prostaglandin F1alpha + NAD+
? + NADH
show the reaction diagram
-
-
-
-
?
6-ketoprostaglandin E1 + NAD+
6,15-diketoprostaglandin E1
show the reaction diagram
-
-
-
?
6-ketoprostaglandin F1alpha + NAD+
6,15-diketoprostaglandin F1alpha + NADH + H+
show the reaction diagram
-
-
-
?
6-ketoprostaglandin F1alpha + NAD+
6,15-diketoprostaglandin F1alpha
show the reaction diagram
-
-
-
?
9,10-phenanthrenequinone + NADH
?
show the reaction diagram
-
-
-
-
?
prostaglandin A1 + NAD+
15-ketoprostaglandin A1 + NADH + H+
show the reaction diagram
-
-
-
-
-
prostaglandin A1 + NAD+
15-ketoprostaglandin A1 + NADH + H+
show the reaction diagram
-
-
-
-
prostaglandin A1 + NAD+
15-ketoprostaglandin A1 + NADH + H+
show the reaction diagram
-
-
-
?
prostaglandin A1 + NAD+
15-ketoprostaglandin A1 + NADH + H+
show the reaction diagram
-
-
-
?
prostaglandin A1 + NAD+
15-ketoprostaglandin A1 + NADH + H+
show the reaction diagram
-
-
-
?
prostaglandin A1 + NAD+
15-ketoprostaglandin A1 + NADH + H+
show the reaction diagram
-
-
-
-
prostaglandin A1 + NAD+
15-ketoprostaglandin A1 + NADH + H+
show the reaction diagram
-
-
-
?
prostaglandin A1 + NAD+
? + NADH
show the reaction diagram
-
-
-
-
?
prostaglandin A2 + NAD+
15-ketoprostaglandin A2 + NADH + H+
show the reaction diagram
-
-
-
-
-
prostaglandin A2 + NAD+
15-ketoprostaglandin A2 + NADH + H+
show the reaction diagram
-
-
-
?
prostaglandin D1 + NAD+
15-ketoprostaglandin D1 + NADH + H+
show the reaction diagram
-
very low activity
-
?
prostaglandin D2 + NAD+
15-ketoprostaglandin D2 + NADH + H+
show the reaction diagram
-
-
-
-
prostaglandin D2 + NAD+
15-ketoprostaglandin D2 + NADH + H+
show the reaction diagram
-
-
-
?
prostaglandin D2 + NAD+
? + NADH
show the reaction diagram
-
-
-
-
?
prostaglandin E1 + NAD+
? + NADH
show the reaction diagram
-
-
-
-
-
prostaglandin E1 + NAD+
? + NADH
show the reaction diagram
-
-
-
-
?
prostaglandin E1 + NAD+
15-ketoprostaglandin E1 + NADH + H+
show the reaction diagram
-
-
-
-
-
prostaglandin E1 + NAD+
15-ketoprostaglandin E1 + NADH + H+
show the reaction diagram
-
-
-
-
?
prostaglandin E2 + NAD+
15-ketoprostaglandin E2 + NADH + H+
show the reaction diagram
-
-
-
-
-
prostaglandin E2 + NAD+
15-ketoprostaglandin E2 + NADH + H+
show the reaction diagram
-
-
-
-
?
prostaglandin E2 + NAD+
15-ketoprostaglandin E2 + NADH + H+
show the reaction diagram
O08699
-
-
-
?
prostaglandin E2 + NAD+
15-ketoprostaglandin E2 + NADH + H+
show the reaction diagram
-
the wild type enzyme is highly active against prostaglandin E2 and NAD+
-
-
?
prostaglandin E2 + NAD+
15-oxoprostaglandin E2 + NADH + H+
show the reaction diagram
-
-
-
-
?
prostaglandin E3 + NAD+
15-keto-prostaglandin E3 + NADH + H+
show the reaction diagram
-
-
-
?
prostaglandin F2alpha + NAD(P)+
15-ketoprostaglandin F2alpha + NADH + H+
show the reaction diagram
-
-
-
-
prostaglandin F2alpha + NAD(P)+
15-ketoprostaglandin F2alpha + NADH + H+
show the reaction diagram
-
-
-
?
prostaglandin F2alpha + NAD(P)+
15-ketoprostaglandin F2alpha + NADH + H+
show the reaction diagram
-
-
-
?
prostaglandin F2alpha + NAD(P)+
15-ketoprostaglandin F2alpha + NADH + H+
show the reaction diagram
-
-
-
-
prostaglandin F2alpha + NAD(P)+
15-ketoprostaglandin F2alpha + NADH + H+
show the reaction diagram
-
-
-
?
prostaglandin F2alpha + NAD(P)+
15-ketoprostaglandin F2alpha + NADH + H+
show the reaction diagram
-
-
-
-
prostaglandin F2alpha + NAD(P)+
15-ketoprostaglandin F2alpha + NADH + H+
show the reaction diagram
-
-
-
?
prostaglandin F2alpha + NAD(P)+
15-ketoprostaglandin F2alpha + NADH + H+
show the reaction diagram
-
specific for NAD+
-
?
prostaglandin F2alpha + NAD(P)+
15-ketoprostaglandin F2alpha + NADH + H+
show the reaction diagram
-
specific for NAD+
-
?
prostaglandin F2alpha + NAD(P)+
15-ketoprostaglandin F2alpha + NADH + H+
show the reaction diagram
-
specific for NAD+
-
?
prostaglandin F2alpha + NAD(P)+
15-ketoprostaglandin F2alpha + NADH + H+
show the reaction diagram
-
NAD+ is much more effective than NADP+
-
?
prostaglandin F2alpha + NAD(P)+
15-ketoprostaglandin F2alpha + NADH + H+
show the reaction diagram
-
NADP+ is more effective than NAD+
-
?
prostaglandin F2alpha + NAD+
15-ketoprostaglandin F2alpha + NADH + H+
show the reaction diagram
-
-
-
-
?
prostaglandin F2alpha + NAD+
? + NADH
show the reaction diagram
-
-
-
-
?
prostaglandin I2 + NAD+
15-ketoprostaglandin I2 + NADH + H+
show the reaction diagram
-
-
-
?
9,10-phenanthrenequinone + NADH
? + H2O2
show the reaction diagram
-
formation of potentially hazardous semiquinones, reaction mechanism, overview
-
-
?
additional information
?
-
-
dexamethasone and phorbol ester play a role in enzyme regulation in erythroleukemia cells
-
-
-
additional information
?
-
-
key enzyme for metabolic inactivation of prostaglandins, enzyme levels are reduced in inflammatory bowel disease involving TNF-alpha
-
-
-
additional information
?
-
-
prostaglandins play an essential role in primate parturition acting on uterine contractility and on cervical ripening
-
-
-
additional information
?
-
-
the enzyme is a tumor suppressor of human breast cancer, expression of the enzyme and the estrogen receptor is correlated, silencing of the enzyme results in enhanced cancer cell proliferation, the enzyme expression is silenced in vivo in cancer cells due to promoter methylation
-
-
-
additional information
?
-
-
the enzyme is an in vivo suppressor of colon tumorigenesis, mechanism of conferring increased susceptibility to colon neoplasia, overview
-
-
-
additional information
?
-
-
the enzyme is involved in anti-proliferative effect of non-steroidal anti-inflammatory drugs COX-1 inhibitors on a medullary thyroid carcinoma cell line
-
-
-
additional information
?
-
-
substrate specificity, overview, no activity with prostaglandin B1
-
-
-
additional information
?
-
-
the enzyme catalyzes specifically the oxidation of the (15S)-hydroxy group of all natural prostaglandins except the B and 19-hydroxylated types
-
-
-
additional information
?
-
-
15-hydroxyprostaglandin dehydrogenase may be repressed by an epigenetic mechanism involving histone deacetylation, resulting in increased prostaglandin E2 activity in tumors
-
-
-
additional information
?
-
Mus musculus C57BL/6J
-
the enzyme is an in vivo suppressor of colon tumorigenesis, mechanism of conferring increased susceptibility to colon neoplasia, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
-
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
-
-
-
r
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
-
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
-
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
Q309F3
-
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
catabolism of (15S)-PGE2
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
first step in prostaglandin catabolism
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
first step in prostaglandin catabolism
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
first step in prostaglandin catabolism
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
first step in prostaglandin catabolism
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
first step in prostaglandin catabolism
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
first step in prostaglnadin catabolism
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
i.e. 15-hydroxyprostaglandin or (15S)-PGE2
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
key step in prostaglandin catabolism, enzyme activation leads to reduced cell proliferation, the enzyme is an antagonist of ibuprofen
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
key step in prostaglandin inactivation
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
PGE2 degradation
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
prostaglandin E2, PGE2, a proinflammatory bioactive lipid, promotes cancer progression by modulating proliferation, apoptosis, and angiogenesis, PGE2 is a downstream product cyclooxygenase and is biochemically inactivated by the enzyme
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
reciprocal regulation of cyclooxygenase-2 and 15-hydroxyprostaglandin dehydrogenase expression in A549 human lung adenocarcinoma cells, overview
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
the enzyme is a putative cyclooxygenase-2 antagonist and and tumor suppressor
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
-
transcriptional regulation and biological functions, the enzyme cooperates with cyclooxygenase-2 to control cellular prostaglandin levels, reciprocal regulation of the two enzymes, overview
-
-
?
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH + H+
show the reaction diagram
Mus musculus C57BL/6J
-
i.e. 15-hydroxyprostaglandin or (15S)-PGE2
-
-
?
(5Z,13E)-11alpha-hydroxy-9,15-dioxoprost-5,13-dienoate + NADH
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate + NAD+
show the reaction diagram
-
-
i.e. 15-hydroxyprostaglandin or (15S)-PGE2
-
r
15-hydroxyprostaglandin + NAD+
15-oxoprostaglandin + NADH + H+
show the reaction diagram
-
physiological inactivation of prostaglandin by catalyzing the first step in catabolism
-
-
15-hydroxyprostaglandin + NAD+
15-oxoprostaglandin + NADH + H+
show the reaction diagram
-
physiological inactivation of prostaglandin by catalyzing the first step in catabolism
-
-
15-hydroxyprostaglandin + NAD+
15-oxoprostaglandin + NADH + H+
show the reaction diagram
-
physiological inactivation of prostaglandin by catalyzing the first step in catabolism
-
-
additional information
?
-
-
dexamethasone and phorbol ester play a role in enzyme regulation in erythroleukemia cells
-
-
-
additional information
?
-
-
key enzyme for metabolic inactivation of prostaglandins, enzyme levels are reduced in inflammatory bowel disease involving TNF-alpha
-
-
-
additional information
?
-
-
prostaglandins play an essential role in primate parturition acting on uterine contractility and on cervical ripening
-
-
-
additional information
?
-
-
the enzyme is a tumor suppressor of human breast cancer, expression of the enzyme and the estrogen receptor is correlated, silencing of the enzyme results in enhanced cancer cell proliferation, the enzyme expression is silenced in vivo in cancer cells due to promoter methylation
-
-
-
additional information
?
-
-
the enzyme is an in vivo suppressor of colon tumorigenesis, mechanism of conferring increased susceptibility to colon neoplasia, overview
-
-
-
additional information
?
-
-
the enzyme is involved in anti-proliferative effect of non-steroidal anti-inflammatory drugs COX-1 inhibitors on a medullary thyroid carcinoma cell line
-
-
-
additional information
?
-
-
15-hydroxyprostaglandin dehydrogenase may be repressed by an epigenetic mechanism involving histone deacetylation, resulting in increased prostaglandin E2 activity in tumors
-
-
-
additional information
?
-
Mus musculus C57BL/6J
-
the enzyme is an in vivo suppressor of colon tumorigenesis, mechanism of conferring increased susceptibility to colon neoplasia, overview
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NAD+
-
much more effective than NADP+
NAD+
-
NADP+ is more effective
NAD+
-
specific for
NAD+
-
specific for; specific for NAD+
NAD+
-
specific for NAD+
NAD+
-
binding structure analysis, determination of interactions
NAD+
O08699
dependent on
NADP+
-
more efficient than NAD+
thio-NAD+
-
5-33% of activity with NAD+ depending on substrate
2-Azido-NAD+
-
2.4% of activity with NAD+
additional information
-
-
-
additional information
-
acetylpyridine dinucleotide can not replace NAD+
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(4-([(4-chlorophenyl)sulfanyl]methyl)phenyl)(4-methylpiperidin-1-yl)methanone
-
-
(4-[(2-bromophenoxy)methyl]phenyl)(piperidin-1-yl)methanone
-
-
(5Z)-5-[3-bromo-4-(2-cyclohexylethoxy)benzylidene]-1,3-thiazolidine-2,4-dione
-
-
(5Z)-5-[3-chloro-4-(2-cyclohexylethoxy)benzylidene]-1,3-thiazolidine-2,4-dione
-
-
(5Z)-5-[3-chloro-4-(3-cyclohexylpropoxy)benzylidene]-1,3-thiazolidine-2,4-dione
-
-
(5Z)-5-[3-chloro-4-(4-cyclohexylbutoxy)benzylidene]-1,3-thiazolidine-2,4-dione
-
-
(5Z)-5-[3-chloro-4-(cyclohexylmethoxy)benzylidene]-1,3-thiazolidine-2,4-dione
-
-
(5Z)-5-[3-chloro-4-(cyclohexyloxy)benzylidene]-1,3-thiazolidine-2,4-dione
-
-
(5Z)-5-[4-(2-cyclohexylethoxy)-3-methoxybenzylidene]-1,3-thiazolidine-2,4-dione
-
-
(5Z)-5-[4-(2-cyclohexylethoxy)-3-methoxybenzylidene]-3-methyl-1,3-thiazolidine-2,4-dione
-
-
(5Z)-5-[4-(2-cyclohexylethoxy)benzylidene]-1,3-thiazolidine-2,4-dione
-
-
(9Z,12E)-13-hydroxyoctadeca-9,12-dienoic acid
-
0.01 mM, 45% inhibition
1,2-naphthoquinone
-
0.0002 mM, time dependent inactivation, 1 mM glutathione or 40% glycerol protect from inactivation; inactivation, glutathione protects
12-O-tetradecanoylphorbol-13-acetate
-
10 nM, rapid loss of activity in eryrthroleukemia cells during 40 min, inhibition can be prevented by staurosporin indicating that protein kinase C is involved
12-O-tetradecanoylphorbol-13-acetate
-
induces the synthesis of 15-PGDH but inhibits the enzyme activity a protein kinase C mediated mechanism
13-cis-Prostaglandin F2alpha
-
; 0.124 mM, 50% inhibition
13-hydroxyperoxyoctadecadienoic acid
-
0.001 mM to 0.01 mM, 50% inhibition with 0.003 mM, uncompetitive inhibition vs. NAD+, noncompetitive vs. prostaglandin E2
15-deoxy-DELTA12,14-prostaglandin J2
-
0.024 mM, 50% inhibition
15-epi-prostaglandin E1
-
-
15-Epiprostaglandin E1
-
0.17 mM, 50% inhibition
15-ketoprostaglandin E1
-
-
15-Ketoprostaglandin E2
-
-
2,4,6-Trinitrobenzenesulfonic acid
-
-
2-([(6-bromo-4H-imidazo[4,5-b]pyridin-2-yl)sulfanyl]methyl)benzonitrile
-
-
2-azido NAD+
-
photoaffinity analog of NAD+, 0.115 mM, complete inactivation
2-hydroxy-5-(3,5-dimethoxycarbonyl-benzoyl)-benzene acetic acid
-
1000 times more potent inhibitor than sulfaphasalazine
2-methyl-1,4-naphthoquinone
-
0.02 mM, time dependent inactivation
3,3',5-triiodothyronine
-
-
3-(2,5-dimethyl-1-phenyl-1H-pyrrol-3-yl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine
-
-
4,5-benzo[a]pyrenequinone
-
0.0002 mM, time dependent inactivation
4-chloromercuriphenylsulfonic acid
-
-
4-methoxybenzyl-2,4-thiazolidinedione
-
-
4-methoxybenzylidene-2,4-thiazolidinedione
-
-
5-(4-((4-methylcyclohexyl)methoxy)benzylidene) thiazolidine-2,4-dione
-
-
5-(4-(2-(thiophen-2-yl)ethoxy)benzylidene)thiazolidine-2,4-dione
-
-
5-(4-(2-(thiophen-3-yl)ethoxy)benzylidene)thiazolidine-2,4-dione
-
-
5-(4-(2-cyclopentylethoxy)benzylidene)thiazolidine-2,4-dione
-
-
5-(4-(4-(chloromethyl)benzyloxy)benzylidene) thiazolidine-2,4-dione
-
-
5-(4-(cyclopentylmethoxy)benzylidene)thiazolidine-2,4-dione
-
-
5-[4-((1-methyl)-cyclohexylmethoxy)benzylidene]-2,4-thiazolidenedione
-
-
5-[4-((1-methyl)-cyclohexylmethoxy)benzyl]-2,4-thiazolidenedione
-
trivial name ciglitazone
5-[4-(benzoxy)benzylidene]-2,4-thiazolidenedione
-
-
5-[4-(cyclohexylbutoxy)benzylidene]-2,4-thiazolidenedione
-
-
5-[4-(cyclohexylethoxy)benzylidene]-2,4-thiazolidenedione
-
-
5-[4-(cyclohexylmethoxy)benzylidene]-2,4-thiazolidenedione
-
-
5-[4-(cyclohexyloxy)benzylidene]-2,4-thiazolidenedione
-
-
5-[4-(cyclohexylpropoxy)benzylidene]-2,4-thiazolidenedione
-
-
5-[[4-(ethoxycarbonyl)phenyl]azo]-2-hydroxy-benzeneacetic acid
-
CAY-10397, specific 15-PGDH inhibitor
5-[[4-(ethoxycarbonyl)phenyl]azo]2-hydroxy-benzene acetic acid
O08699
CAY-10397
7,8-benzo[a]pyrenequinone
-
0.0002 mM, time dependent inactivation, 40% glycerol protects from inactivation; inactivation, glutathione protects
-
7-Oxa-13-prostynoic acid
-
; 0.0475 mM, 50% inhibition
7-oxa-prostanoic acid
-
-
7-Oxoprostanoic acid
-
-
7-Thia-13-prostynoic acid
-
; 0.0068 mM, 50% inhibition
7-thia-prostanoic acid
-
-
Acetylsalicylate
-
-
acrolein
-
irreversible inhibition
adenosine-5'-diphosphoribose
-
-
arachidonic acid
-
0.0027 mM, 50% inhibition; irreversible inactivation
arachidonic acid
-
-
Berberine
-
0.023 mM, 50% inhibition
Biochanin A
-
0.031 mM, 50% inhibition
CAY 10397
-
specific inhibitor, completely reverses the stimulating effect of ibuprofen on cell proliferation in TT cells
chalcone
-
0.016 mM, 50% inhibition
chrysin
-
0.021 mM, 50% inhibition
ciglitazone
-
-
ciglitazone
-
0.003 mM, 50% inhibition
Cu2+
-
0.05 mM to 0.5 mM, 50% inhibition with 0.1 mM, uncompetitive vs. NAD+, non-competitive vs. prostaglandin E2
curcumin
-
0.01 mM, 50% inhibition
diethyldicarbonate
-
-
DuP 697
-
0.022 mM, 50% inhibition
ent-13-dehydro-15-epi-prostaglandin F2alpha
-
-
Ent-13-dehydro-15-epiprostaglandin F3alpha
-
0.055 mM, 50% inhibition
Ent-13-dehydroprostaglandin E2
-
; 0.0068 mM, 50% inhibition
epi-7-thia-prostaglandin F2alpha
-
-
epi-7-thiaprostaglandin F2alpha
-
0.0052 mM, 50% inhibition
epigallocatechin gallate
-
0.012 mM, 50% inhibition
Ethacrynic acid
-
0.0055 mM, 50% inhibition; irreversible inactivation
Ethacrynic acid
-
-
ethanol
-
slight inhibition
Flufenamic acid
-
0.041 mM, 50% inhibition
Flurbiprofen
-
0.062 mM, 50% inhibition
genistein
-
-
glycerol
-
slight inhibition
hexadecanoic acid
-
0.01 mM
ICI 81008
-
-
indomethacin
-
-
indomethacin
-
0.066 mM, 50% inhibition
ketorolac
-
0.028 mM, 50% inhibition
linoleic acid
-
0.01 mM, 30% inhibition
Meclofenamic acid
-
0.073 mM, 50% inhibition
Mefenamic acid
-
0.076 mM, 50% inhibition
mixture of endogenous fatty acids
-
mixture contains palmitic acid, stearic acid linoleic acid and oleic acid, competitive vs. prostaglandine E2
-
N-(2-phenylethyl)-indomethacin amide
-
0.098 mM, 50% inhibition
N-(3-pyridyl)-indomethacin amide
-
0.1 mM, 50% inhibition
N-Chlorosuccinimide
-
-
N-ethylmaleimide
-
-
N-ethylmaleimide
-
-
NAD+
-
-
NAD+
-
product inhibition
nat-13-dehydroprostaglandin E2
-
-
nat-13-dehydroprostaglandin F3alpha
-
-
Nat-13-thiaprostaglandin F2alpha
-
0.0088 mM, 50% inhibition
-
nat-7-thia-prostaglandin F2alpha
-
-
nat-l3-dehydroprostaglandin F2alpha
-
-
niflumic acid
-
0.058 mM, 50% inhibition
nimesulide
-
0.051 mM, 50% inhibition
NS 398
-
0.064 mM, 50% inhibition
octadecanoic acid
-
0.01 mM
p-Chloromercuriphenylsulfonic acid
-
-
papaverine
-
; the inhibition is noncompetitive with prostaglandin E2, uncompetitive with NAD+, and reversible
papaverine
-
-
papaverine
-
; the inhibition is noncompetitive with prostaglandin E2, uncompetitive with NAD+, and reversible
PD 98059
-
an ERK kinase inhibitor
Phenylglyoxal
-
-
Prostaglandin B1
-
; 0.0497 mM, 50% inhibition
Prostaglandin B1
-
-
prostaglandin E1
-
-
prostaglandin E2
-
-
prostaglandin E2
-
product inhibition
prostaglandin F2alpha
-
-
Prostanoic acid
-
; 0.013 mM, 50% inhibition
Prostanoic acid
-
-
pyridoxal 5'-phosphate
-
-
resveratrol
-
0.054 mM, 50% inhibition
rosiglitazone
-
-
rosiglitazone
-
0.026 mM, 50% inhibition
sulfaphasalazine
-
anticolitic drug
-
sulindac
-
0.041 mM, 50% inhibition
sulindac sulfide
-
0.018 mM, 50% inhibition
sulindac sulfone
-
0.038 mM, 50% inhibition
tetradecanoic acid
-
0.01 mM
Tetraiodothyroacetic acid
-
-
Tetranitromethane
-
-
troglitazone
-
-
troglitazone
-
0.34 mM, 50% inhibition
Zn2+
-
0.05 mM to 0.5 mM, 50% inhibition with 0.15 mM, uncompetitive vs. NAD+, non-competitive vs. prostaglandin E2
[1-(3-methylphenyl)-1H-benzimidazol-5-yl](piperidin-1-yl)methanone
-
-
[4-(4-methoxyphenyl)piperazin-1-yl](4-[(phenylsulfanyl)methyl]phenyl)methanone
-
-
MK 886
-
0.037 mM, 50% inhibition
additional information
-
not inhibited by L-thyronine and NADH
-
additional information
-
-
-
additional information
-
not inhibited by thyroid hormones and NADPH
-
additional information
-
IC50 values at pH 7.0 and at pH 9.0; pH-dependent inhibition and inhibition mechanism, at high substrate concentrations there is formation of unreactive complexes between the 15-hydroxyrostaglandin and both the free enzyme and enzyme-NADH complex and between the 15-ketoprostaglandin and both the free enzyme and enzyme NAD+ complex
-
additional information
-
no inhibition by Ca2+
-
additional information
-
not inhibited by 10 mM to 80 mM ethanol
-
additional information
-
not inhibitited by iodoacetimide
-
additional information
-
TNF-alpha suppresses the enzyme expression in colonocytes
-
additional information
-
histone deacetylase inhibitors, such as sodium butyrate, scriptaid, apicidin, and oxamflatin, and transforming growth factor-beta, TGF-beta1, induce enzyme expression in lung adenocarcinoma cells, overview
-
additional information
-
the enzyme expression is suppressed by the epidermal growth factor via snail which interacts through its zinc finger structure, mechanism overview
-
additional information
-
enzyme down-regulation by estrogen
-
additional information
-
interleukin-1beta suppresses the enzyme expression, as well as down-regulation of cyclooxygenase-2 expression, whereas down-regulation of cyclooxygenase-1 has no effect on 15-PGDH expression, overview
-
additional information
-
bile acids activate the signal transduction pathway protein kinase C-> extracellular signal-regulated kinase 1/2-> early growth response factor-1-> Snail and thereby suppress 15-PGDH transcription, unconjugated bile acids are much more potent inhibitors of 15-PGDH expression and activity than related conjugated bile acids, chenodeoxycholate and deoxycholate suppress the transcription of 15-PGDH resulting in reduced amounts of mRNA, protein, and enzyme activity
-
additional information
-
histone deacetylase 2 and the transcriptional regulator Snail play a central role in the suppression of 15-PGDH expression
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
17beta-estradiol
-
slight activation
corticosterone
-
4fold activation
cortisone
-
5fold activation
cyclooxygenase-1 inhibitors
-
selective or not
-
dexamethasone
-
10fold activation
dihydrotestosterone
-
-
erlotinib
-
epidermal growth factor receptor tyrosine kinase inhibitor, trreatment of cells increases the expression of the enzyme in a subset of non-small-cell lung cancer lines
pioglitazone
-
upregulation of expression, involving peroxisome proliferator-activated receptor gamma. Upregulation results in reduced production of prostaglandin E2 and finally inhibition of lung cancer growth
Prednisolone
-
6fold activation
progesterone
-
-
progesterone
-
activates, 7fold activation
rosiglitazone
-
upregulation of expression, involving peroxisome proliferator-activated receptor gamma. Upregulation results in reduced production of prostaglandin E2 and finally inhibition of lung cancer growth
sulindac sulfone
-
-
testosterone
-
-
testosterone
-
2fold activation
Thionicotinamide adenine dinucleotide
-
5-33% of the activity with NAD+, depending on substrate; can replace NAD+
Thionicotinamide adenine dinucleotide
-
5-33% of the activity with NAD+, depending on substrate
Triamcinolone
-
7fold activation
estradiol
-
2fold activation
additional information
-
no activation by cAMP
-
additional information
-
a 42- to 55-fold induction of the PGDH activity is observed after 20 days of gestation in pregnant rabbits
-
additional information
-
the enzyme is induced by the androgens dihydrotestosterone or testosterone and, to a lesser extent, by 17beta-estradiol and progesterone in androgen-sensitive LNCaP cells, not in hormone-independent PC3 cells, the induction of 15-PGDH is not blocked by steroid receptor antagonist RU 486 nor by antiandrogen, flutamide, but is inhibited by tyrosine kinase inhibitor, genistein, and by ERK kinase inhibitor, PD 98059, but not by protein kinase C inhibitor GF109203X, thus androgens induce 15-PGDH gene expression through an unconventional nongenomic pathway, no induction by dexamethasone, hydrocortisone, and RU 486
-
additional information
-
12-O-tetradecanoylphorbol-13-acetate induces the synthesis of 15-PGDH but inhibits the enzyme activity a protein kinase C mediated mechanism
-
additional information
-
enzyme up-regulation by the tumor suppressor gene CAAT/enhancer binding protein alpha
-
additional information
-
enzyme expression is inducible by indomethacin in LS174T cells, but not in HCA-7 and HCT-15 cells, and also not in enzyme-deficient HCT-116
-
additional information
-
enzyme activation leads to reduced cell proliferation
-
additional information
-
15-PGDH expression is increased by hepatocyte nuclear factor 3beta in lung cancer cells
-
additional information
-
flurbiprofen induces 15-PGDH expression in cancer cells, PD98059 and U-0126 elevate 15-PGDH levels very significantly
-
additional information
-
treatment of colorectal cancer cells with 5-aza-2'-deoxycytidine, 5 mM sodium butyrate or 5 mM valproic acid induces an increase in 15-PGDH protein expression
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0012
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate
-
37C, pH 7.5, I17L mutant
0.0026
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate
-
37C, pH 7.5, N91D mutant
0.0034
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate
-
37C, pH 7.5
0.0035
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate
-
37C, pH 7.5, V186K mutant
0.0039
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate
-
-
0.0045
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate
-
37C, pH 7.5, V186A mutant
0.006
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate
-
37C, pH 7.5, N91A mutant
0.0063
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate
-
37C, pH 7.5
0.0071
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate
-
37C, pH 7.5
0.0086
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate
-
37C, pH 7.5, T11S mutant
0.01
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate
-
pH 7.4, 37C
0.011
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate
-
37C, pH 7.5, I17A mutant; 37C, pH 7.5, I17V mutant
0.013
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate
-
37C, pH 7.5, Q15K/W37K double mutant
0.022
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate
-
37C, pH 7.5, V186I mutant
0.026
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate
-
37C, pH 7.5, Q15K mutant
0.00765
(5Z,8E,10E,12S)-12-hydroxy-5,8,10-heptadecatrienoic acid
-
-
0.012
(5Z,8E,10E,12S)-12-hydroxy-5,8,10-heptadecatrienoic acid
-
-
0.016
15-hydroxyeicosatetraenoic acid
-
-
0.0521
15-ketoprostaglandin E1
-
at pH 7.0
0.0266
15-Ketoprostaglandin E2
-
at pH 9.0
0.0528
15-Ketoprostaglandin E2
-
at pH 7.0
0.077
19-hydroxyprostaglandin E1
-
-
0.283
20-hydroxyprostaglandin E1
-
-
0.066
6-ketoprostaglandin E1
-
-
0.111
6-ketoprostaglandin F1alpha
-
-
0.022
NAD+
-
recombinant enzyme expressed in E. coli
0.022
NAD+
-
37C, pH 7.5, V186K mutant
0.0227
NAD+
-
at pH 9.0, + prostaglandin E2
0.024
NAD+
-
37C, pH 7.5, V186A mutant
0.0284
NAD+
-
at pH 7.0, + prostaglandin E2
0.029
NAD+
-
at pH 9.0, + prostaglandin E1
0.03
NAD+
-
37C, pH 7.5
0.0308
NAD+
-
at pH 7.0, + prostaglandin E1
0.032
NAD+
-
37C, pH 7.5
0.032
NAD+
-
37C, pH 7.5, N91D mutant
0.038
NAD+
-
37C, pH 7.5
0.0384
NAD+
-
-
0.0399
NAD+
-
+ prostaglandin F2alpha
0.0405
NAD+
-
+ prostaglandin E2
0.0451
NAD+
-
+ prostaglandin E1
0.046
NAD+
-
-
0.059
NAD+
-
37C, pH 7.5, I17L mutant
0.098
NAD+
-
37C, pH 7.5, I17V mutant
0.11
NAD+
-
-
0.117
NAD+
-
-
0.27
NAD+
-
37C, pH 7.5, V186I mutant
0.55
NAD+
-
37C, pH 7.5, I17A mutant
0.7
NAD+
-
37C, pH 7.5, T11S mutant
0.72
NAD+
-
37C, pH 7.5, N91A mutant
0.0156
NADH
-
at pH 7.0, + 15-keto-PGE1; at pH 7.0, + 15-ketoprostaglandin E2
0.0594
NADH
-
at pH 9.0, + 15-ketoprostaglandin E2
0.0045
Prostaglandin A1
-
recombinant enzyme expressed in E. coli
0.033
Prostaglandin A1
-
-
0.038
Prostaglandin A1
-
-
0.003
Prostaglandin A2
-
-
0.022
Prostaglandin A2
-
recombinant enzyme expressed in E. coli
0.741
Prostaglandin D2
-
-
0.0013
prostaglandin E1
-
at pH 7.0
0.0013
prostaglandin E1
-
-
0.0034
prostaglandin E1
-
-
0.0048
prostaglandin E1
-
at pH 9.0
0.0048
prostaglandin E1
-
-
0.005
prostaglandin E1
-
recombinant enzyme expressed in E. coli
0.0054
prostaglandin E1
-
-
0.027
prostaglandin E1
-
-
0.033
prostaglandin E1
-
; pH 10.2
0.033
prostaglandin E1
-
-
0.00158
prostaglandin E2
-
-
0.0025
prostaglandin E2
-
at pH 7.0
0.0026
prostaglandin E2
-
-
0.0028
prostaglandin E2
-
at pH 9.0
0.0028
prostaglandin E2
-
pH 8.0, 25C, 20 nM [1-(3-methylphenyl)-1H-benzimidazol-5-yl](piperidin-1-yl)methanone
0.0037
prostaglandin E2
-
pH 8.0, 25C, 10 nM [1-(3-methylphenyl)-1H-benzimidazol-5-yl](piperidin-1-yl)methanone
0.0039
prostaglandin E2
-
recombinant enzyme expressed in E. coli
0.0055
prostaglandin E2
-
pH 8.0, 25C
0.0056
prostaglandin E2
-
pH 8.0, 25C, 4 nM 3-(2,5-dimethyl-1-phenyl-1H-pyrrol-3-yl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine
0.0064
prostaglandin E2
-
pH 8.0, 25C, 10 nM 3-(2,5-dimethyl-1-phenyl-1H-pyrrol-3-yl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine
0.0075
prostaglandin E2
-
pH 8.0, 25C, 10 nM 2-([(6-bromo-4H-imidazo[4,5-b]pyridin-2-yl)sulfanyl]methyl)benzonitrile
0.01
prostaglandin E2
-
-
0.0117
prostaglandin E2
-
-
0.0135
prostaglandin E2
-
pH 8.0, 25C, 10 nM 2-([(6-bromo-4H-imidazo[4,5-b]pyridin-2-yl)sulfanyl]methyl)benzonitrile
0.014
prostaglandin E2
-
-
0.059
prostaglandin E2
-
; pH 10.2
0.059
prostaglandin E2
-
-
0.077
prostaglandin E3
-
-
0.0213
prostaglandin F2alpha
-
-
0.025
prostaglandin F2alpha
-
-
0.04
prostaglandin F2alpha
-
recombinant enzyme expressed in E. coli
0.059
prostaglandin F2alpha
-
-
0.133
prostaglandin F2alpha
-
-
0.063
6-oxo-prostaglandin F1alpha
-
recombinant enzyme expressed in E. coli
additional information
additional information
-
Michaelis-Menten kinetics, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
37
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate
-
37C, pH 7.5, V186K mutant
45
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate
-
37C, pH 7.5, N91D mutant
50
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate
-
37C, pH 7.5
73
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate
-
37C, pH 7.5, N91A mutant
78
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate
-
37C, pH 7.5, V186A mutant
127
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate
-
37C, pH 7.5, I17A mutant
143
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate
-
37C, pH 7.5, I17V mutant
210
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate
-
37C, pH 7.5, I17L mutant
262
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-5,13-dienoate
-
37C, pH 7.5, V186I mutant
35
NAD+
-
37C, pH 7.5, V186K mutant
42
NAD+
-
37C, pH 7.5, N91D mutant
47
NAD+
-
37C, pH 7.5
70
NAD+
-
37C, pH 7.5, V186A mutant
91
NAD+
-
37C, pH 7.5, N91A mutant
110
NAD+
-
37C, pH 7.5, I17V mutant
129
NAD+
-
37C, pH 7.5, I17A mutant
165
NAD+
-
37C, pH 7.5, I17L mutant
247
NAD+
-
37C, pH 7.5, V186I mutant
6.1
prostaglandin E2
-
pH 8.0, 25C, 20 nM [1-(3-methylphenyl)-1H-benzimidazol-5-yl](piperidin-1-yl)methanone
7.5
prostaglandin E2
-
pH 8.0, 25C, 10 nM 3-(2,5-dimethyl-1-phenyl-1H-pyrrol-3-yl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine
10.3
prostaglandin E2
-
pH 8.0, 25C, 10 nM [1-(3-methylphenyl)-1H-benzimidazol-5-yl](piperidin-1-yl)methanone
11.1
prostaglandin E2
-
pH 8.0, 25C, 4 nM 3-(2,5-dimethyl-1-phenyl-1H-pyrrol-3-yl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine
12.4
prostaglandin E2
-
pH 8.0, 25C, 10 nM 2-([(6-bromo-4H-imidazo[4,5-b]pyridin-2-yl)sulfanyl]methyl)benzonitrile
13.6
prostaglandin E2
-
pH 8.0, 25C
14.1
prostaglandin E2
-
pH 8.0, 25C, 10 nM 2-([(6-bromo-4H-imidazo[4,5-b]pyridin-2-yl)sulfanyl]methyl)benzonitrile
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
900
prostaglandin E2
-
pH 8.0, 25C, 10 nM 2-([(6-bromo-4H-imidazo[4,5-b]pyridin-2-yl)sulfanyl]methyl)benzonitrile
913
1200
prostaglandin E2
-
pH 8.0, 25C, 10 nM 3-(2,5-dimethyl-1-phenyl-1H-pyrrol-3-yl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine
913
1800
prostaglandin E2
-
pH 8.0, 25C, 10 nM 2-([(6-bromo-4H-imidazo[4,5-b]pyridin-2-yl)sulfanyl]methyl)benzonitrile
913
2000
prostaglandin E2
-
pH 8.0, 25C, 4 nM 3-(2,5-dimethyl-1-phenyl-1H-pyrrol-3-yl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine
913
2100
prostaglandin E2
-
pH 8.0, 25C, 20 nM [1-(3-methylphenyl)-1H-benzimidazol-5-yl](piperidin-1-yl)methanone
913
2500
prostaglandin E2
-
pH 8.0, 25C
913
2800
prostaglandin E2
-
pH 8.0, 25C, 10 nM [1-(3-methylphenyl)-1H-benzimidazol-5-yl](piperidin-1-yl)methanone
913
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.26
15-ketoprostaglandin E1
-
substrate prostaglandin E1
0.02
15-Ketoprostaglandin E2
-
prostaglandin E2 as the variable substrate
0.031
15-Ketoprostaglandin E2
-
NAD+ as the variable substrate
0.62
4-methoxybenzyl-2,4-thiazolidinedione
-
37C, pH 7.5
0.017
4-methoxybenzylidene-2,4-thiazolidinedione
-
37C, pH 7.5
0.0006
5-[4-((1-methyl)-cyclohexylmethoxy)benzylidene]-2,4-thiazolidenedione
-
37C, pH 7.5
0.0022
5-[4-((1-methyl)-cyclohexylmethoxy)benzyl]-2,4-thiazolidenedione
-
37C, pH 7.5
0.0012
5-[4-(benzoxy)benzylidene]-2,4-thiazolidenedione
-
37C, pH 7.5
0.005
5-[4-(cyclohexylbutoxy)benzylidene]-2,4-thiazolidenedione
-
37C, pH 7.5
0.00009
5-[4-(cyclohexylethoxy)benzylidene]-2,4-thiazolidenedione
-
37C, pH 7.5
0.00027
5-[4-(cyclohexylmethoxy)benzylidene]-2,4-thiazolidenedione
-
37C, pH 7.5
0.0009
5-[4-(cyclohexyloxy)benzylidene]-2,4-thiazolidenedione
-
37C, pH 7.5
0.02
adenosine-5'-diphosphoribose
-
prostaglandin E2 as the variable substrate
0.225
adenosine-5'-diphosphoribose
-
NAD+ as the variable substrate
0.117
NAD+
-
substrate prostaglandin E1
0.163
NAD+
-
substrate prostaglandin F2alpha
0.168
NAD+
-
substrate prostaglandin E2
0.0135
NADH
-
NAD+ as the variable substrate
0.015
NADH
-
substrate prostaglandin E1
0.026
papaverine
-
; pH 7.4, 37C
0.068
papaverine
-
enzyme from kidney; kidney enzyme, pH 7.4, 37C
0.07
papaverine
-
enzyme from heart; heart enzyme, pH 7.4, 37C
0.098
papaverine
-
pH 7.4, 37C
0.098
papaverine
-
-
0.12
papaverine
-
; pH 7.4, 37C
0.4
papaverine
-
; kidney enzyme, pH 7.4, 37C
0.0139
prostaglandin E1
-
-
0.0109
prostaglandin E2
-
-
0.0873
prostaglandin F2alpha
-
-
0.14
indomethacin
-
-
additional information
additional information
-
inhibition kinetics
-
additional information
additional information
-
0.0189, endogenous mixture of palmitic, stearic, oleic and linoleic acid
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000631
(4-([(4-chlorophenyl)sulfanyl]methyl)phenyl)(4-methylpiperidin-1-yl)methanone
-
pH 8, 25C
0.000089
(4-[(2-bromophenoxy)methyl]phenyl)(piperidin-1-yl)methanone
-
pH 8, 25C
0.000019
(5Z)-5-[3-bromo-4-(2-cyclohexylethoxy)benzylidene]-1,3-thiazolidine-2,4-dione
-
pH and temperature not specified in the publication
0.000008
(5Z)-5-[3-chloro-4-(2-cyclohexylethoxy)benzylidene]-1,3-thiazolidine-2,4-dione
-
pH and temperature not specified in the publication
0.00001
(5Z)-5-[3-chloro-4-(3-cyclohexylpropoxy)benzylidene]-1,3-thiazolidine-2,4-dione
-
pH and temperature not specified in the publication
0.000024
(5Z)-5-[3-chloro-4-(4-cyclohexylbutoxy)benzylidene]-1,3-thiazolidine-2,4-dione
-
pH and temperature not specified in the publication
0.000028
(5Z)-5-[3-chloro-4-(cyclohexylmethoxy)benzylidene]-1,3-thiazolidine-2,4-dione
-
pH and temperature not specified in the publication
0.000047
(5Z)-5-[3-chloro-4-(cyclohexyloxy)benzylidene]-1,3-thiazolidine-2,4-dione
-
pH and temperature not specified in the publication
0.000025
(5Z)-5-[4-(2-cyclohexylethoxy)-3-methoxybenzylidene]-1,3-thiazolidine-2,4-dione
-
pH and temperature not specified in the publication
0.05
(5Z)-5-[4-(2-cyclohexylethoxy)-3-methoxybenzylidene]-3-methyl-1,3-thiazolidine-2,4-dione
-
pH and temperature not specified in the publication
0.000051
(5Z)-5-[4-(2-cyclohexylethoxy)benzylidene]-1,3-thiazolidine-2,4-dione
-
pH and temperature not specified in the publication
0.000141
2-([(6-bromo-4H-imidazo[4,5-b]pyridin-2-yl)sulfanyl]methyl)benzonitrile
-
pH 8, 25C
0.00089
3-(2,5-dimethyl-1-phenyl-1H-pyrrol-3-yl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine
-
pH 8, 25C
0.000052
5-(4-((4-methylcyclohexyl)methoxy)benzylidene) thiazolidine-2,4-dione
-
pH 7.5, temperature not specified in the publication
0.000031
5-(4-(2-(thiophen-2-yl)ethoxy)benzylidene)thiazolidine-2,4-dione
-
pH 7.5, temperature not specified in the publication
0.00006
5-(4-(2-(thiophen-3-yl)ethoxy)benzylidene)thiazolidine-2,4-dione
-
pH 7.5, temperature not specified in the publication
0.000116
5-(4-(2-cyclopentylethoxy)benzylidene)thiazolidine-2,4-dione
-
pH 7.5, temperature not specified in the publication
0.000124
5-(4-(4-(chloromethyl)benzyloxy)benzylidene) thiazolidine-2,4-dione
-
pH 7.5, temperature not specified in the publication
0.000045
5-(4-(cyclopentylmethoxy)benzylidene)thiazolidine-2,4-dione
-
pH 7.5, temperature not specified in the publication
0.000056
[1-(3-methylphenyl)-1H-benzimidazol-5-yl](piperidin-1-yl)methanone
-
pH 8, 25C
0.01
[4-(4-methoxyphenyl)piperazin-1-yl](4-[(phenylsulfanyl)methyl]phenyl)methanone
-
value above, pH 8, 25C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.000077
-
enzyme activity in kidney cortex
0.00083
-
recombinant 15-PGDH
0.0014
-
enzyme from lung
0.0098
-
enzyme from kidney cortex
0.025
-
enzyme from heart, substrate prostaglandin E2
0.136
-
enzyme from brain, substrate prostaglandin E2
1.75
-
-
1.765
-
-
1.791
-
-
7.79
-
purified native enzyme
12.15
-
enzyme from placenta
13.2
-
assay at 37C
19.8
-
recombinant enzyme
24
-
enzyme from placenta
25
-
; purified enzyme
70
-
enzyme from lung
additional information
-
purified enzyme
additional information
-
activity during pregnancy, substrate specificity
additional information
-
6.1 pmol/min per 1000000 cells, enzyme activity in LNCaP cells
additional information
-
in vivo activity in absence and presence of different androgens, overview
additional information
Q309F3
enzyme activity in the endometrium during the oestrous cycle and early pregnancy, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 9
-
assay at
7
-
assay at
7.5 - 8.8
-
sharp optimum
8
-
assay at
8.7
-
assay at
9
Q309F3
assay at
10 - 10.4
-
; prostaglandin E1, 3-(cyclohexylamine)propanesulfonic acid buffer
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 10
-
strong increase in activity between pH 8.0 and 9.5, sharp decrease above
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
-
assay at
25
Q309F3
assay at
25
-
assay at
37
-
assay at
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
lung adenocarcinoma cell line
Manually annotated by BRENDA team
-
up-regulation of cyclooxygenase-2 expression by pro-inflammatory cytokines is accompanied by down-regluation of 15-hydroxyprostaglandin dehydrogenase expression. Over-expression of cyclooxygenase-2 but not -1 also attenuates 15-hydroxyprostaglandin dehydrogenase expression. Similarly, overexpression of 15-hydroxyprostaglandin dehydrogenase inhibits interleukin 1beta-induced cyclooxygenase-2 expression and results in apoptosis. The levels of 15-hydroxyprostaglandin dehydrogenase expression in transfected cells correlate positively with those of mesenchymal markers, and negatively with those of epithelial markers
Manually annotated by BRENDA team
-
non-small cell lung carcinoma cell line A549, expression of 15-PGDH is induced by dexamethason, prednisolone, betamethasone and triamcinolone
Manually annotated by BRENDA team
-
both 15-hydroxyprostaglandin dehydrogenase mRNA and protein levels are significantly higher in kidney cortex than in papilla. Enzyme is mainly localized to the tubular epithelial cells in kidney cortex and outer medulla
Manually annotated by BRENDA team
-
55000 Da form of enzyme, level increases with preterm premature rupture of membrane
Manually annotated by BRENDA team
-
expression of the enzyme and the estrogen receptor is correlated
Manually annotated by BRENDA team
-
extravillous trophoblasts layer
Manually annotated by BRENDA team
-
in preterm chorion, levles of 15-hydroxyprostaglandin dehydrogenase protein and activity are lower when compared to term, and are further reduced with the presence of infection. Preterm premature rapture of membranes and subclinical inflammation do not affect the levels of 29000 Da 15-hydroxyprostaglandin dehydrogenase protein in the fetal membranes
Manually annotated by BRENDA team
-
distribution of enzyme expression within the tissue in situ, overview
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
distribution of enzyme expression within the tissue in situ, overview
-
Manually annotated by BRENDA team
-
highly reduced enzyme expression in colon cancers, distribution of enzyme expression within the tissue in situ, overview
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
highly reduced enzyme expression in colon cancers, distribution of enzyme expression within the tissue in situ, overview
-
Manually annotated by BRENDA team
-
the enzyme expression is down-regulated
Manually annotated by BRENDA team
-
low expression
Manually annotated by BRENDA team
-
low enzyme expression level
Manually annotated by BRENDA team
-
low enzyme expression level
Manually annotated by BRENDA team
-
lung adenocarcinoma cell line
Manually annotated by BRENDA team
-
15-hydroxyprostaglandin dehydrogenase is expressed mainly in keratinocytes and melanocytes
Manually annotated by BRENDA team
-
low enzyme expression level
Manually annotated by BRENDA team
-
erythroleukemia cell line
Manually annotated by BRENDA team
-
very low enzyme expression level
Manually annotated by BRENDA team
-
colon cancer cell line
Manually annotated by BRENDA team
-
invasiveapocrine carcinoma cells correspond to a distinct molecular subtype of breast carcinomas characterized by the expression of 15-prostaglandin dehydrogenase alone or in combination with a novel form of acyl-CoA synthetase medium-chain family member 1, 15-prostaglandin dehydrogenase is not expressed by other breast cancer types
Manually annotated by BRENDA team
-
in hair follicle, 15-hydroxyprostaglandin dehydrogenase is expressed mainly in keratinocytes and melanocytes
Manually annotated by BRENDA team
-
medulla, cortex
Manually annotated by BRENDA team
-
very low expression level
Manually annotated by BRENDA team
-
low enzyme expression level
Manually annotated by BRENDA team
-
intense immunofluorescent staining for 15-hydroxyprostaglandin dehydrogenase in macula densa and glomerulus of cyclooxygenase-2 knock-out mice
Manually annotated by BRENDA team
-
high enzyme expression level
Manually annotated by BRENDA team
-
very low enzyme expression level
Manually annotated by BRENDA team
-
high enzyme expression level
Manually annotated by BRENDA team
-
of 28-days-old pregnant rabbits
Manually annotated by BRENDA team
-
loss of 15-hydroxyprostaglandin expression in 65% of lung cancers. Enzyme acts as a tumor suppressor in lung cancer
Manually annotated by BRENDA team
-
intense immunofluorescent staining for 15-hydroxyprostaglandin dehydrogenase in macula densa and glomerulus of cyclooxygenase-2 knock-out mice
Manually annotated by BRENDA team
-
high enzyme expression level
Manually annotated by BRENDA team
-
low enzyme expression level
Manually annotated by BRENDA team
-
in hair follicle, 15-hydroxyprostaglandin dehydrogenase is expressed mainly in keratinocytes and melanocytes
Manually annotated by BRENDA team
-
high expression level of 15-PGDH
Manually annotated by BRENDA team
-
macula densa cell line, significantly lower enzyme levels than in a proximal tubule cell line. Treatment with an inhibitor of cyclooxygenase-2 increases enzyme level
Manually annotated by BRENDA team
-
enzyme activity is reduced in inflamed mucosa
Manually annotated by BRENDA team
-
NSCLC cell, much lower expression of 15-hydroxyprostaglandin dehydrogenase in all NSCLC histologic groups compared with healthy lung cell. Treatment with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib increases the expression of the enzyme in a subset of NSCLC lines
Manually annotated by BRENDA team
-
reduced expression of 15-PGDH occurrs in tumor cells and is paralleled by decreased 15-PGDH activity in tumors, the amount of 15-PGDH is frequently decreased in NSCLC cells compared with adjacent normal lung
Manually annotated by BRENDA team
-
low enzyme expression level
Manually annotated by BRENDA team
-
PGDH protein is concentrated in the parietal yolk sac membrane (PYS) lining the placental surface and in placental blood vessels
Manually annotated by BRENDA team
-
androgen-sensitive cancer cells LNCaP and hormone-independent PC3 cells, enzyme expression is induced by steroids
Manually annotated by BRENDA team
-
very low expression level
Manually annotated by BRENDA team
-
intense immunofluorescent staining for 15-hydroxyprostaglandin dehydrogenase in macula densa and glomerulus of cyclooxygenase-2 knock-out mice
Manually annotated by BRENDA team
-
enzyme is mainly localized to the tubular epithelial cells in kidney cortex and outer medulla
Manually annotated by BRENDA team
-
low expression level of 15-PGDH
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
-
-
Manually annotated by BRENDA team
-
low enzyme expression level
Manually annotated by BRENDA team
-
very low enzyme expression level
Manually annotated by BRENDA team
-
very low enzyme expression level
Manually annotated by BRENDA team
-
low enzyme expression level
Manually annotated by BRENDA team
Q309F3
the enzyme is expressed mainly in the glandular epithelium, enzyme activity during the oestrous cycle and early pregnancy, overview
Manually annotated by BRENDA team
-
PGDH messenger RNA (mRNA) abundance decreases significantly in the visceral yolk sac membrane and the amnion throughout the last third of pregnancy
Manually annotated by BRENDA team
additional information
-
tissue distribution, overview
Manually annotated by BRENDA team
additional information
-
a 42- to 55-fold induction of the PGDH activity is observed after 20 days of gestation in pregnant rabbits
Manually annotated by BRENDA team
additional information
-
distribution of enzyme expression in normal and pathological tissues, overview, no enzyme expression in spleen, heart, HCT-116 cells, CacO-2 cells and Colo 201 cells
Manually annotated by BRENDA team
additional information
-
enzyme expression analysis, PGDH expression is repressed in multiple human cancers
Manually annotated by BRENDA team
additional information
-
tissue distribution of enzyme expression, overview, no expression in heart and brain
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
subcellular localization, overview
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
24500
-
gel filtration
285914
28000
-
gel filtration, MALDI-MS
285935
29000
-
recombinant enzyme expressed in E. coli, western-blot
285937
31000
-
wild type recombinant protein, SDS-PAGE
689129
32000
-
gel filtration in the presence of mercaptoethanol
285919
40000
-
gel filtration
285926
51500
-
gel filtration
285915, 285923
54000
-
gel filtration
285922
55000
-
gel filtration
285925
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 29000, SDS-PAGE
?
-
x * 29000, SDS-PAGE
dimer
-
2 * 29000, SDS-PAGE
dimer
-
2 * 29000, SDS-PAGE
dimer
-
2 * 28900, deduced from nucleotide sequence
monomer
-
1 * 42000, SDS-PAGE
monomer
-
1 * 24000, SDS-PAGE
monomer
-
1 * 28000, SDS-PAGE
monomer
-
1 * 29000, recombinant enzyme, SDS-PAGE
additional information
-
primary structure
additional information
-
molecular modeling
additional information
-
structure analysis using the tertiary complex crystal structure of the enzyme with bound NAD+ and 15-hydroxyprostaglandin, homology modeling, docking and molecular dynamics simulation, three-dimensional structure model, detailed overview
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
modeling of structure for mutant A140P. Mutation disrupts binding of the substrate prostaglandin E2 both because the pyrrolidine ring of Pro140 fills a space that in the wildtype complex is occupied by the prostaglandin E2 target side-chain 15-OH and because there is a resulting loss of catalytically important hydrogen bonding of the 15-OH to the nearby serine at residue 138
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
-
when expression is induced at 37C, almost all wild type recombinant HPGD protein is soluble
689129
41.2
-
melting point at pH 8.0, ligand free
726267
45.9
-
melting point at pH 8.0, in the presence of NAD+
726267
52.5
-
melting point at pH 8.0, in the presence of NADH
726267
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
glycerol, 50%, stabilizes
-
NAD+ stabilizes
-
no stabilization by addition of prostaglandins
-
the assay mix containing 50 mM Tris HCl, pH 7.5, 1 mM dithiothreitol, 100 mM prostaglandin E2 and 1 mM NAD+ at 22C is not optimal for HPGD activity, but avoids a sharp, unphysiological pH optimum around pH 9
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, 20% glycerol, 4 weeks, no loss of activity
-
-20C, 5 mM potassium phosphate, pH 7.0, 50% glycerol, 1 mM EDTA, 7 months, 10% loss of activity
-
-20C, 50% glycerol, 10 mM 2-mercaptoethanol, stable for at least 1 year
-
-20C, 50% glycerol, 2 months, 8% loss of activity
-
-20C, purified enzyme in a buffer containing 50% glycerol, 5 mM potassium phosphate, pH 7.0, and 1 mM EDTA, loss less than 10% of its initial activity in 2 months
-
4C, 20% glycerol, 4 weeks, 25% loss of activity
-
-80C, 3-4 weeks
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
; native enzyme from lung by ammonium sulfate fractionation and acetone precipitation
-
recombinant His-tagged lung enzyme from Escherichia coli by nickel affinity chromatography
Q309F3
native soluble enzyme partially from heart ventricular tissue by ultracentrifugation, ammonium sulfate fractionation, gel filtration, and anion exchange chromatography; partial
-
native enzyme partially from heart; native soluble enzyme partially from lung by ultracentrifugation, ammonium sulfate fractionation and anion exchange chromatography; partial
-
CM-Sepharose, DEAE-Sepharose, Blue Sepharose, Mono-Q
-
nickel-Sepharose column chromatography
-
recombinant 15-PGDH
-
; native enzyme 2600fold from lung cytosol of pregnant rabbits, by cation and anion exchange chromatography, gel filtration, hydrophobic interaction and hydroxylapatite chromatography to homogeneity
-
partial
-
native enzyme partially from kidney; partial
-
native soluble enzyme partially from lung; partial
-
partial
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
15-PGDH, DNA and amino acid sequence determination and analysis, functional overexpression of His-tagged lung enzyme in Escherichia coli
Q309F3
DNA and amino acid sequence, expression analysis and transcriptional regulation, overview
-
enzyme expression analysis
-
expressed in Escherichia coli
-
expressed in Escherichia coli as a His-tagged fusion protein
-
expressed in Escherichia coli strain JM109(DE3); expression in Escherichia coli
-
expressed in Mus musculus RAW macrophages (R15L cells)
-
expression in Escherichia coli
-
expression of 15-PGDH as GST-fusion in Escherichia coli
-
stable expression of wild-type and mutant enzymes in AD-293 cells using an adenovirus shuttle vector
-
transient expression in HT29 cells
-
cloning of cDNA
-
expression in 293-T cell, together with mouse peroxisome proliferator-activated receptor gamma
-
expression in IEC-18 cell
O08699
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
15-PGDH is overexpressed in malignant ovarian tissue
-
interleukin 4 induces up-regulation of 15-PGDH expression in A549 cells as well as in other lung cancer cell lines
-
PDGH shows little expression in the myometrium
-
PGDH messenger RNA (mRNA) abundance decreases significantly in the visceral yolk sac membrane and the amnion throughout the last third of pregnancy
-
PGDH protein is robustly expressed in the visceral yolk sac epithelium and mesoderm, correlating strongly with PGDH mRNA levels
-
PGDH protein is highly expressed in the endometrial epithelium
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A13G/A14S/Q15K/D36S/W37R
-
no activity
A140P
-
naturally occuring mutation in patients with pulmonary hypertropic osteoarthropathy. Homozygous individuals develop pulmonary hypertrophic osteoarthropathy secondary to chronically elevated prostaglandin E2 levels. Heterozygous relatives also show milder biochemical and clinical manifestations. After expression in Escherichia coli, the mutations renders the protein largely insoluble at 37C, but mostly souble at 20C. Mutant exhibits less than 1.5% of wild-type activity, the mutant shows no detectable activity, the A140P substitution renders the enzyme largely insoluble at 37C, at 27C, the mutant protein is partially soluble, and at 20C it is mostly soluble
A14S/Q15K/D36S/W37R
-
no activity
C152A
-
similar activity as wild-type
C152F
-
no activity
C182A
-
no activity
C182F
-
no activity
C42A
-
similar activity as wild-type
C45F
-
similar activity as wild-type
C63A
-
similar activity as wild-type
C63F
-
10% of wild-type activity
D64E
-
no activity
D64K
-
low activity
D64N
-
similar activity as wild type
D86E
-
similar activity as wild type
D86N
-
similar activity as wild type
I17A
-
270% of wild-type activity
I17E
-
no activity
I17K
-
no activity
I17L
-
364% of wild-type activity
I17V
-
300% of wild-type activity
K155L
-
inactive enzyme
K155Q
-
inactive enzyme
L155L
-
no activity
N91A
-
136% of wild-type activity
N91D
-
86% of wild-type activity
N91K
-
no activity
N91L
-
no activity
Q15K
-
approx. 200% of wild-type activity
Q15K/D36A/W37R
-
no activity with NAD+ as cofactor, low activity with NADP+ as cofactor
Q15K/D36S/W37R
-
no activity with NAD+ as cofactor, low activity with NADP+ as cofactor
Q15K/W37K
-
approx. 350% of wild-type activity
Q15K/W37R
-
approx. 350% of wild-type activity, strong activity with NADP+ as cofactor
Q15R
-
approx. 100% of wild-type activity
Q15R/W37K
-
approx. 200% of wild-type activity
Q15R/W37R
-
approx. 200% of wild-type activity, strong activity with NADP+ as cofactor
S138A
-
no activity
S193P
-
the missense mutation in exon 6 of the human HPGD gene encoding NAD+ dependent 15-hydroxyprostaglandin dehydrogenase is involved in the pathogenesis of isolated congenital nail clubbing
T11A
-
no activity
T11C
-
no activity
T11S
-
110% of wild-type activity
T188A
-
no activity
T188S
-
substantial activity, lower than wild-type
T188Y
-
no activity
V186A
-
143% of wild-type activity
V186D
-
no activity
V186I
-
468% of wild-type activity
V186K
-
71% of wild-type activity
W37K
-
approx. 100% of wild-type activity
W37R
-
approx. 100% of wild-type activity
Y151A
-
no activity
Y151A
-
inactive enzyme
Y151F
-
no activity
Y151F
-
inactive enzyme
Y151F
-
site-directed mutagenesis, highly reduced activity compared to the enzyme
Y151L/K155E
-
inactive
Y151S
-
no activity
L155Q
-
no activity
additional information
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C-terminal truncation decreases activity
additional information
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enzyme silencing by RNAi method
additional information
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identfication of catalytically important residues by site-directed mutagenesis
additional information
-
injection of wild-type enzyme, but not mutant enzyme, into mice transfected with A549 cells, reduces the ability of the cancer cell to proliferate in the mice, transfected A549 cells overexpressing the enzyme undergo apoptosis, overview
additional information
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interleukin-1beta suppresses the enzyme expression, as well as down-regulation of cyclooxygenase-2 expression, whereas down-regulation of cyclooxygenase-1 has no effect on 15-PGDH expression, overview, silencing of IL-1beta-induced expression of COX-2 by RNAi method
additional information
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identification of an insertion-deletion mutation in 15-hydroxyprostaglandin dehydrogenase exon 3, this alters the open reading frame from codon 78, truncating the protein after ten altered amino acids, and of a homozygous 2-bp deletion within the duplicated dinucleotide CTCT at nucleotides 175 and 176. This alters the reading frame from residue 59 and truncates the HPGD protein at residue 65 after seven altered amino acids. Both of these predicted truncated proteins lack the entire PGE2-binding domain and cause primary hypertrophic asteoarthropathy
additional information
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up-regulation of cyclooxygenase-2 expression by pro-inflammatory cytokines is accompanied by down-regluation of 15-hydroxyprostaglandin dehydrogenase expression. Over-expression of cyclooxygenase-2 but not -1 also attenuates 15-hydroxyprostaglandin dehydrogenase expression. Similarly, overexpression of 15-hydroxyprostaglandin dehydrogenase inhibits interleukin 1beta-induced cyclooxygenase-2 expression and results in apoptosis. The levels of 15-hydroxyprostaglandin dehydrogenase expression in transfected cells correlate positively with those of mesenchymal markers, and negatively with those of epithelial markers
Y151S
-
inactive enzyme
additional information
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15-hydroxyprostaglandin dehydrogenase hypomorphic mice show a decreased level of enzyme mRNA and activity in all tissues examined. Mice show spontaneous preterm labor in the absence of progesterone withdrawal, and the onset of labor is preceded by prematurely increased concentrations of prostaglandin E2 and F2alpha. The fetal genotype plays a role in birth timing
additional information
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overexpression of 15-hydroxyprostaglandin dehydrogenase significantly increases peroxisome proliferator-activated receptor gamma-mediated transcription in a prostaglandin E2-dependent manner
additional information
O08699
expression in nontumorigenic IEC-18 cells, with and without K-RasV12 and analysis of the ability of cells to form tumors in nu/nu mice. Transformed cells show increased 15-hydroxyprostaglandin dehydrogenase activity with decreased prostaglandin E2 and prostaglandin I2 levels, cyclooxygenase-2 and microsomal prostaglandin E synthase-1 expression and proliferation rates. Xenografts of cells expressing both the enzyme and K-RasV12 exhibit delayed tumor formation with negligible cyclooxygenase-2 and microsomal prostaglandin E synthase-1 expression and significantly decreased prostaglandin E2 levels. Tumors have decreased staining of the proliferative marker, Ki-67, and a significant increase in apoptosis in the central region of the tumor
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
A140P is a naturally occuring mutation in patients with pulmonary hypertrophic osteoarthropathy. Homozygous individuals develop pulmonary hypertrophic osteoarthropathy secondary to chronically elevated prostaglandin E2 levels. Heterozygous relatives also show milder biochemical and clinical manifestations. Identification of an insertion-deletion mutation in 15-hydroxyprostaglandin dehydrogenase exon 3, this alters the open reading frame from codon 78, truncating the protein after ten altered amino acids, and of a homozygous 2-bp deletion within the duplicated dinucleotide CTCT at nucleotides 175 and 176. This alters the reading frame from residue 59 and truncates the HPGD protein at residue 65 after seven altered amino acids. Both of these predicted truncated proteins lack the entire PGE2-binding domain and cause primary hypertrophic osteoarthropathy
medicine
-
in non-small-cell lung cancer cells, i.e. NSCLC cells, much lower expression of 15-hydroxyprostaglandin dehydrogenase in all histologic groups compared with healthy lung cell. Treatment with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib increases the expression of the enzyme in a subset of NSCLC lines
medicine
-
loss of 15-hydroxyprostaglandin expression in 65% of lung cancers. Enzyme acts as a tumor suppressor in lung cancer and is a direct downstream effector of hepatocyte nuclear factor 3beta
medicine
-
thiazolidinediones rosiglitazone and pioglitazone upregulate expression of 15-hydroxyprostaglandin dehydrogenase, involving peroxisome proliferator-activated receptor gamma. Upregulation results in reduced production of prostaglandin E2 and finally inhibition of lung cancer growth
medicine
-
up-regulation of cyclooxygenase-2 expression by pro-inflammatory cytokines is accompanied by down-regluation of 15-hydroxyprostaglandin dehydrogenase expression. Over-expression of cyclooxygenase-2 but not -1 also attenuates 15-hydroxyprostaglandin dehydrogenase expression. Similarly, overexpression of 15-hydroxyprostaglandin dehydrogenase inhibits interleukin 1beta-induced cyclooxygenase-2 expression and results in apoptosis. The levels of 15-hydroxyprostaglandin dehydrogenase expression in transfected cells correlate positively with those of mesenchymal markers, and negatively with those of epithelial markers
medicine
-
15-hydroxyprostaglandin dehydrogenase hypomorphic mice show a decreased level of enzyme mRNA and activity in all tissues examined. Mice show spontaneous preterm labor in the absence of progesterone withdrawal, and the onset of labor is preceded by prematurely increased concentrations of prostaglandin E2 and F2alpha. The fetal genotype plays a role in birth timing
medicine
O08699
expression in nontumorigenic IEC-18 cells, with and without K-RasV12 and analysis of the ability of cells to form tumors in nu/nu mice. Transformed cells show increased 15-hydroxyprostaglandin dehydrogenase activity with decreased prostaglandin E2 and prostaglandin I2 levels, cyclooxygenase-2 and microsomal prostaglandin E synthase-1 expression and proliferation rates. Xenografts of cells expressing both the enzyme and K-RasV12 exhibit delayed tumor formation with negligible cyclooxygenase-2 and microsomal prostaglandin E synthase-1 expression and significantly decreased prostaglandin E2 levels. Tumors have decreased staining of the proliferative marker, Ki-67, and a significant increase in apoptosis in the central region of the tumor, PGDH expression suppresses K-RasV12-mediated tumorigenesis in intestinal epithelial cells