BRENDA - Enzyme Database show

Identification of key residues determining species differences in inhibitor binding of microsomal prostaglandin E synthase-1

Pawelzik, S.C.; Uda, N.R.; Spahiu, L.; Jegerschoeld, C.; Stenberg, P.; Hebert, H.; Morgenstern, R.; Jakobsson, P.J.; J. Biol. Chem. 285, 29254-29261 (2010)

Data extracted from this reference:

Cloned(Commentary)
EC Number
Commentary
Organism
5.3.99.3
expressed in Escherichia coli BL21Star (DE) pLysS cells
Homo sapiens
5.3.99.3
expressed in Escherichia coli BL21Star (DE) pLysS cells
Rattus norvegicus
Engineering
EC Number
Amino acid exchange
Commentary
Organism
5.3.99.3
T131V/L135F/A138F
the mutant shows bout 4fold reduced specific activity towards prostaglandin H2 compared to the wild type enzyme and is not inhibited by 1-C-(2-chlorobenzene)-3-N-(naphthalen-1-yl)benzene-1,3-dicarboxamide
Homo sapiens
5.3.99.3
V131T/F135L/F138A
the mutant shows bout 4fold increased specific activity towards prostaglandin H2 compared to the wild type enzyme and is inhibited by 1-C-(2-chlorobenzene)-3-N-(naphthalen-1-yl)benzene-1,3-dicarboxamide
Rattus norvegicus
Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
5.3.99.3
(4E)-4-[2-(3-bromophenyl)hydrazin-1-ylidene]-1-ethanethioyl-3-methyl-4,5-dihydro-1H-pyrazol-5-one
-
Homo sapiens
5.3.99.3
(4E)-4-[2-(3-bromophenyl)hydrazin-1-ylidene]-1-ethanethioyl-3-methyl-4,5-dihydro-1H-pyrazol-5-one
-
Rattus norvegicus
5.3.99.3
2-chloro-N-[3-(naphthalen-1-ylcarbamoyl)phenyl]benzamide
selective for human over rat MPGES1
Homo sapiens
5.3.99.3
2-chloro-N-[3-(naphthalen-1-ylcarbamoyl)phenyl]benzamide
inhibitor of mutant enzyme V131T/F135L/F138A, but not of the wild type enzyme
Rattus norvegicus
Localization
EC Number
Localization
Commentary
Organism
GeneOntology No.
Textmining
5.3.99.3
microsome
-
Homo sapiens
-
-
5.3.99.3
microsome
-
Rattus norvegicus
-
-
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
Prostaglandin H2
Homo sapiens
-
Prostaglandin E2
-
-
?
5.3.99.3
Prostaglandin H2
Rattus norvegicus
-
Prostaglandin E2
-
-
?
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
5.3.99.3
Homo sapiens
-
-
-
5.3.99.3
Rattus norvegicus
-
-
-
Specific Activity [micromol/min/mg]
EC Number
Specific Activity Minimum [µmol/min/mg]
Specific Activity Maximum [µmol/min/mg]
Commentary
Organism
5.3.99.3
0.054
-
mutant enzyme T131V/L135F/A138F, in 0.1 M potassium phosphate buffer, pH 7.4, 2.5 mM glutathione, at 4°C
Homo sapiens
5.3.99.3
0.059
-
wild type enzyme, in 0.1 M potassium phosphate buffer, pH 7.4, 2.5 mM glutathione, at 4°C
Rattus norvegicus
5.3.99.3
0.086
-
mutant enzyme V131T/F135L/F138A, in 0.1 M potassium phosphate buffer, pH 7.4, 2.5 mM glutathione, at 4°C
Rattus norvegicus
5.3.99.3
0.214
-
wild type enzyme, in 0.1 M potassium phosphate buffer, pH 7.4, 2.5 mM glutathione, at 4°C
Homo sapiens
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
5.3.99.3
Prostaglandin H2
-
715541
Homo sapiens
Prostaglandin E2
-
-
-
?
5.3.99.3
Prostaglandin H2
-
715541
Rattus norvegicus
Prostaglandin E2
-
-
-
?
Cofactor
EC Number
Cofactor
Commentary
Organism
Structure
5.3.99.3
glutathione
-
Rattus norvegicus
5.3.99.3
glutathione
-
Homo sapiens
IC50 Value
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
5.3.99.3
0.000058
-
wild type enzyme, in 0.1 M potassium phosphate buffer, pH 7.4, 2.5 mM glutathione, at 4°C
Homo sapiens
2-chloro-N-[3-(naphthalen-1-ylcarbamoyl)phenyl]benzamide
5.3.99.3
0.00059
-
mutant enzyme V131T/F135L/F138A, in 0.1 M potassium phosphate buffer, pH 7.4, 2.5 mM glutathione, at 4°C
Rattus norvegicus
2-chloro-N-[3-(naphthalen-1-ylcarbamoyl)phenyl]benzamide
Cloned(Commentary) (protein specific)
EC Number
Commentary
Organism
5.3.99.3
expressed in Escherichia coli BL21Star (DE) pLysS cells
Homo sapiens
5.3.99.3
expressed in Escherichia coli BL21Star (DE) pLysS cells
Rattus norvegicus
Cofactor (protein specific)
EC Number
Cofactor
Commentary
Organism
Structure
5.3.99.3
glutathione
-
Rattus norvegicus
5.3.99.3
glutathione
-
Homo sapiens
Engineering (protein specific)
EC Number
Amino acid exchange
Commentary
Organism
5.3.99.3
T131V/L135F/A138F
the mutant shows bout 4fold reduced specific activity towards prostaglandin H2 compared to the wild type enzyme and is not inhibited by 1-C-(2-chlorobenzene)-3-N-(naphthalen-1-yl)benzene-1,3-dicarboxamide
Homo sapiens
5.3.99.3
V131T/F135L/F138A
the mutant shows bout 4fold increased specific activity towards prostaglandin H2 compared to the wild type enzyme and is inhibited by 1-C-(2-chlorobenzene)-3-N-(naphthalen-1-yl)benzene-1,3-dicarboxamide
Rattus norvegicus
IC50 Value (protein specific)
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
5.3.99.3
0.000058
-
wild type enzyme, in 0.1 M potassium phosphate buffer, pH 7.4, 2.5 mM glutathione, at 4°C
Homo sapiens
2-chloro-N-[3-(naphthalen-1-ylcarbamoyl)phenyl]benzamide
5.3.99.3
0.00059
-
mutant enzyme V131T/F135L/F138A, in 0.1 M potassium phosphate buffer, pH 7.4, 2.5 mM glutathione, at 4°C
Rattus norvegicus
2-chloro-N-[3-(naphthalen-1-ylcarbamoyl)phenyl]benzamide
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
5.3.99.3
(4E)-4-[2-(3-bromophenyl)hydrazin-1-ylidene]-1-ethanethioyl-3-methyl-4,5-dihydro-1H-pyrazol-5-one
-
Homo sapiens
5.3.99.3
(4E)-4-[2-(3-bromophenyl)hydrazin-1-ylidene]-1-ethanethioyl-3-methyl-4,5-dihydro-1H-pyrazol-5-one
-
Rattus norvegicus
5.3.99.3
2-chloro-N-[3-(naphthalen-1-ylcarbamoyl)phenyl]benzamide
selective for human over rat MPGES1
Homo sapiens
5.3.99.3
2-chloro-N-[3-(naphthalen-1-ylcarbamoyl)phenyl]benzamide
inhibitor of mutant enzyme V131T/F135L/F138A, but not of the wild type enzyme
Rattus norvegicus
Localization (protein specific)
EC Number
Localization
Commentary
Organism
GeneOntology No.
Textmining
5.3.99.3
microsome
-
Homo sapiens
-
-
5.3.99.3
microsome
-
Rattus norvegicus
-
-
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
Prostaglandin H2
Homo sapiens
-
Prostaglandin E2
-
-
?
5.3.99.3
Prostaglandin H2
Rattus norvegicus
-
Prostaglandin E2
-
-
?
Specific Activity [micromol/min/mg] (protein specific)
EC Number
Specific Activity Minimum [µmol/min/mg]
Specific Activity Maximum [µmol/min/mg]
Commentary
Organism
5.3.99.3
0.054
-
mutant enzyme T131V/L135F/A138F, in 0.1 M potassium phosphate buffer, pH 7.4, 2.5 mM glutathione, at 4°C
Homo sapiens
5.3.99.3
0.059
-
wild type enzyme, in 0.1 M potassium phosphate buffer, pH 7.4, 2.5 mM glutathione, at 4°C
Rattus norvegicus
5.3.99.3
0.086
-
mutant enzyme V131T/F135L/F138A, in 0.1 M potassium phosphate buffer, pH 7.4, 2.5 mM glutathione, at 4°C
Rattus norvegicus
5.3.99.3
0.214
-
wild type enzyme, in 0.1 M potassium phosphate buffer, pH 7.4, 2.5 mM glutathione, at 4°C
Homo sapiens
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
Prostaglandin H2
-
715541
Homo sapiens
Prostaglandin E2
-
-
-
?
5.3.99.3
Prostaglandin H2
-
715541
Rattus norvegicus
Prostaglandin E2
-
-
-
?