BRENDA - Enzyme Database show

Microsomal prostaglandin E synthase type 2 (mPGES2) is a glutathione-dependent heme protein, and dithiothreitol dissociates the bound heme to produce active prostaglandin E2 synthase in vitro

Takusagawa, F.; J. Biol. Chem. 288, 10166-10175 (2013)

Data extracted from this reference:

Activating Compound
EC Number
Activating Compound
Commentary
Organism
Structure
5.3.99.3
dithiothreitol
leads to dissociation of the bound heme which is hindered by imidazole
Macaca fascicularis
5.3.99.3
GSH
mPGES2 has a GSH-binding motif, the GSH molecule binds at the predicted amino acid residues 148VPxL to 164DSxxI. GSH is essential for heme binding to isozyme mPGES2, structures of GSH-heme complex-binding cavity in isozyme mPGES2, overview
Macaca fascicularis
Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
5.3.99.3
heme
heme is bound to the enzyme subunits and alters the enzyme catalytic specificity, overview. Heme is attached to the bound GSH by an iron-sulfur bond, but heme cannot bind to mPGES2 in the absence of GSH, other sulfhydryl compounds, such as DTT and 2-mercaptoethanol, are unable to promote heme binding to isozyme mPGES2. Bound heme is oxidized by H2O2, but it does not dissociate from mPGES2
Macaca fascicularis
5.3.99.3
imidazole
imidazole stacks on the bound heme and inhibits heme oxidation by H2O2, heme dissociation by DTT, and catalytic activity
Macaca fascicularis
Localization
EC Number
Localization
Commentary
Organism
GeneOntology No.
Textmining
5.3.99.3
membrane
membrane-associated prostaglandin E synthase-2
Macaca fascicularis
16020
-
5.3.99.3
microsome
-
Macaca fascicularis
-
-
Natural Substrates/ Products (Substrates)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
5.3.99.3
(5Z,13E,15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
Macaca fascicularis
reaction of heme-free isozyme mPGES2
(5Z,13E,15S)-11alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate
-
-
?
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
5.3.99.3
Macaca fascicularis
Q9N0A4
isozyme mPGES2
-
Source Tissue
EC Number
Source Tissue
Commentary
Organism
Textmining
5.3.99.3
liver
-
Macaca fascicularis
-
5.3.99.3
additional information
abundant tissue distribution of isozyme mPGES2
Macaca fascicularis
-
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
5.3.99.3
(5Z,13E,15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
reaction of heme-free isozyme mPGES2
727942
Macaca fascicularis
(5Z,13E,15S)-11alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate
-
-
-
?
5.3.99.3
additional information
heme-free isozyme mPGES2 and heme-bound isozyme mPGES2 catalyze isomerization of prostaglandin H2 to prostaglandin E2 and conversion of prostaglandin H2 to to (12S)-hydroxy-(5Z,8E,10E)-heptadecatrienoic acid and malondialdehyde, respectively
727942
Macaca fascicularis
?
-
-
-
-
Temperature Optimum [°C]
EC Number
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
5.3.99.3
4
-
assay at
Macaca fascicularis
pH Optimum
EC Number
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
5.3.99.3
7.2
-
assay at
Macaca fascicularis
Activating Compound (protein specific)
EC Number
Activating Compound
Commentary
Organism
Structure
5.3.99.3
dithiothreitol
leads to dissociation of the bound heme which is hindered by imidazole
Macaca fascicularis
5.3.99.3
GSH
mPGES2 has a GSH-binding motif, the GSH molecule binds at the predicted amino acid residues 148VPxL to 164DSxxI. GSH is essential for heme binding to isozyme mPGES2, structures of GSH-heme complex-binding cavity in isozyme mPGES2, overview
Macaca fascicularis
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
5.3.99.3
heme
heme is bound to the enzyme subunits and alters the enzyme catalytic specificity, overview. Heme is attached to the bound GSH by an iron-sulfur bond, but heme cannot bind to mPGES2 in the absence of GSH, other sulfhydryl compounds, such as DTT and 2-mercaptoethanol, are unable to promote heme binding to isozyme mPGES2. Bound heme is oxidized by H2O2, but it does not dissociate from mPGES2
Macaca fascicularis
5.3.99.3
imidazole
imidazole stacks on the bound heme and inhibits heme oxidation by H2O2, heme dissociation by DTT, and catalytic activity
Macaca fascicularis
Localization (protein specific)
EC Number
Localization
Commentary
Organism
GeneOntology No.
Textmining
5.3.99.3
membrane
membrane-associated prostaglandin E synthase-2
Macaca fascicularis
16020
-
5.3.99.3
microsome
-
Macaca fascicularis
-
-
Natural Substrates/ Products (Substrates) (protein specific)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
5.3.99.3
(5Z,13E,15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
Macaca fascicularis
reaction of heme-free isozyme mPGES2
(5Z,13E,15S)-11alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate
-
-
?
Source Tissue (protein specific)
EC Number
Source Tissue
Commentary
Organism
Textmining
5.3.99.3
liver
-
Macaca fascicularis
-
5.3.99.3
additional information
abundant tissue distribution of isozyme mPGES2
Macaca fascicularis
-
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
5.3.99.3
(5Z,13E,15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
reaction of heme-free isozyme mPGES2
727942
Macaca fascicularis
(5Z,13E,15S)-11alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate
-
-
-
?
5.3.99.3
additional information
heme-free isozyme mPGES2 and heme-bound isozyme mPGES2 catalyze isomerization of prostaglandin H2 to prostaglandin E2 and conversion of prostaglandin H2 to to (12S)-hydroxy-(5Z,8E,10E)-heptadecatrienoic acid and malondialdehyde, respectively
727942
Macaca fascicularis
?
-
-
-
-
Temperature Optimum [°C] (protein specific)
EC Number
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
5.3.99.3
4
-
assay at
Macaca fascicularis
pH Optimum (protein specific)
EC Number
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
5.3.99.3
7.2
-
assay at
Macaca fascicularis
Expression
EC Number
Organism
Commentary
Expression
5.3.99.3
Macaca fascicularis
iron does not induce the enzyme expression
additional information
Expression (protein specific)
EC Number
Organism
Commentary
Expression
5.3.99.3
Macaca fascicularis
iron does not induce the enzyme expression
additional information