BRENDA - Enzyme Database show

Prostaglandin F2alpha formation from prostaglandin H2 by prostaglandin F synthase (PGFS): crystal structure of PGFS containing bimatoprost

Komoto, J.; Yamada, T.; Watanabe, K.; Woodward, D.F.; Takusagawa, F.; Biochemistry 45, 1987-1996 (2006)

Data extracted from this reference:

Cloned(Commentary)
EC Number
Commentary
Organism
1.1.1.188
expressed in Escherichia coli HB101 cells; expression in Escherichia coli strain HB101
Homo sapiens
Crystallization (Commentary)
EC Number
Crystallization
Organism
1.1.1.188
in complex with bimatoprost and NADPH, hanging drop vapor diffusion method, using 1.0 mM BMP, 1.0 mM NADPH, 0.14 M NaCl, 50 mM MES buffer (pH 7.0), and 26% (w/v) PEG 8000; purified recombinant enzyme in complex with NADPH and bimatoprost BMP, an ocular hypotensive agent bound near the PGD2 binding site located on the alpha- and omega-chains, hanging drop vapour diffusion method, from 50 mM MES, pH 7.0, containing 7 mg/ml protein, 0.14 M NaCl, 26% w/v PEG 8000, 1.0 mM NADPH, and 1.0 mM BMP, added in a 95% ethanol solution, 4C, 14 days, thick plate-shaped crystals, X-ray diffraction structure determination and analysis at 2.0 A resolution
Homo sapiens
Engineering
EC Number
Amino acid exchange
Commentary
Organism
1.1.1.188
Y55F
site-directed mutagenesis, the mutant loses its PGD2 11-ketoreductase activity, but not the PGH2 9,11-endoperoxide reductase; the mutated enzyme loses the prostaglandin D2 11-ketoreductase activity but retains the prostaglandin H2 9,-11-endoperoxide reductase activity
Homo sapiens
Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
1.1.1.188
9,10-phenanthrenequinone
the prostaglandin D2 11-ketoreductase activity of PGFS is competitively inhibited by 9,10-phenanthrenequinone
Homo sapiens
1.1.1.188
bimatoprost
inhibits the prostaglandin D2 11-ketoreductase activity as well as the prostaglandin H2 9,11-endoperoxide reductase activity of PGFS
Homo sapiens
Natural Substrates/ Products (Substrates)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
1.1.1.188
additional information
Homo sapiens
the enzyme has dual activity as PGD2 11-ketoreductase and PGH2 9,11-endoperoxide reductase
?
-
-
-
1.1.1.188
prostaglandin D2 + NADPH
Homo sapiens
-
9alpha,11beta-prostaglandin F2alphabeta + NADP+
-
-
?
1.1.1.188
prostaglandin H2 + NADPH
Homo sapiens
-
9alpha,11alpha-prostaglandin F2alpha + NADP+
-
-
?
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
1.1.1.188
Homo sapiens
-
-
-
1.1.1.188
Homo sapiens
P42330
-
-
Purification (Commentary)
EC Number
Commentary
Organism
1.1.1.188
; recombinant enzyme from Escherichia coli strain HB101 to homogeneity
Homo sapiens
Reaction
EC Number
Reaction
Commentary
Organism
1.1.1.188
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+ = (5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH + H+
catalytic mechanisms, the catalytic sites for PGD2 11-ketoreductase and PGH2 9,11-endoperoxide reductase activities are located differently in the active site cavity, residue Y55 is important for the PGD2 11-ketoreductase activity, but not for the PGH2 9,11-endoperoxide reductase activity, involved structural features, overview
Homo sapiens
Source Tissue
EC Number
Source Tissue
Commentary
Organism
Textmining
1.1.1.188
lung
;
Homo sapiens
-
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
1.1.1.188
additional information
the enzyme has dual activity as PGD2 11-ketoreductase and PGH2 9,11-endoperoxide reductase
667713
Homo sapiens
?
-
-
-
-
1.1.1.188
additional information
PGFS does not catalyze the reduction of prostaglandin E2
667713
Homo sapiens
?
-
-
-
-
1.1.1.188
prostaglandin D2 + NADPH
-
667713
Homo sapiens
9alpha,11beta-prostaglandin F2alphabeta + NADP+
-
-
-
?
1.1.1.188
prostaglandin D2 + NADPH + H+
-
667713
Homo sapiens
prostaglandin 9alpha,11beta-F2 + NADP+
-
-
-
-
1.1.1.188
prostaglandin H2 + NADPH
-
667713
Homo sapiens
9alpha,11alpha-prostaglandin F2alpha + NADP+
-
-
-
?
1.1.1.188
prostaglandin H2 + NADPH + H+
-
667713
Homo sapiens
prostaglandin F2alpha + NADP+
-
-
-
?
Temperature Optimum [C]
EC Number
Temperature Optimum [C]
Temperature Optimum Maximum [C]
Commentary
Organism
1.1.1.188
30
-
assay at, PGH2 9,11-endoperoxide reductase activity
Homo sapiens
1.1.1.188
37
-
assay at, PGD2 11-ketoreductase activity
Homo sapiens
pH Optimum
EC Number
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
1.1.1.188
6.5
-
assay at, PGD2 11-ketoreductase activity and PGH2 9,11-endoperoxide reductase activity
Homo sapiens
Cofactor
EC Number
Cofactor
Commentary
Organism
Structure
1.1.1.188
NADPH
;
Homo sapiens
Cloned(Commentary) (protein specific)
EC Number
Commentary
Organism
1.1.1.188
expressed in Escherichia coli HB101 cells
Homo sapiens
1.1.1.188
expression in Escherichia coli strain HB101
Homo sapiens
Cofactor (protein specific)
EC Number
Cofactor
Commentary
Organism
Structure
1.1.1.188
NADPH
-
Homo sapiens
Crystallization (Commentary) (protein specific)
EC Number
Crystallization
Organism
1.1.1.188
in complex with bimatoprost and NADPH, hanging drop vapor diffusion method, using 1.0 mM BMP, 1.0 mM NADPH, 0.14 M NaCl, 50 mM MES buffer (pH 7.0), and 26% (w/v) PEG 8000
Homo sapiens
1.1.1.188
purified recombinant enzyme in complex with NADPH and bimatoprost BMP, an ocular hypotensive agent bound near the PGD2 binding site located on the alpha- and omega-chains, hanging drop vapour diffusion method, from 50 mM MES, pH 7.0, containing 7 mg/ml protein, 0.14 M NaCl, 26% w/v PEG 8000, 1.0 mM NADPH, and 1.0 mM BMP, added in a 95% ethanol solution, 4C, 14 days, thick plate-shaped crystals, X-ray diffraction structure determination and analysis at 2.0 A resolution
Homo sapiens
Engineering (protein specific)
EC Number
Amino acid exchange
Commentary
Organism
1.1.1.188
Y55F
site-directed mutagenesis, the mutant loses its PGD2 11-ketoreductase activity, but not the PGH2 9,11-endoperoxide reductase
Homo sapiens
1.1.1.188
Y55F
the mutated enzyme loses the prostaglandin D2 11-ketoreductase activity but retains the prostaglandin H2 9,-11-endoperoxide reductase activity
Homo sapiens
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
1.1.1.188
9,10-phenanthrenequinone
the prostaglandin D2 11-ketoreductase activity of PGFS is competitively inhibited by 9,10-phenanthrenequinone
Homo sapiens
1.1.1.188
bimatoprost
inhibits the prostaglandin D2 11-ketoreductase activity as well as the prostaglandin H2 9,11-endoperoxide reductase activity of PGFS
Homo sapiens
Natural Substrates/ Products (Substrates) (protein specific)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
1.1.1.188
additional information
Homo sapiens
the enzyme has dual activity as PGD2 11-ketoreductase and PGH2 9,11-endoperoxide reductase
?
-
-
-
1.1.1.188
prostaglandin D2 + NADPH
Homo sapiens
-
9alpha,11beta-prostaglandin F2alphabeta + NADP+
-
-
?
1.1.1.188
prostaglandin H2 + NADPH
Homo sapiens
-
9alpha,11alpha-prostaglandin F2alpha + NADP+
-
-
?
Purification (Commentary) (protein specific)
EC Number
Commentary
Organism
1.1.1.188
-
Homo sapiens
1.1.1.188
recombinant enzyme from Escherichia coli strain HB101 to homogeneity
Homo sapiens
Source Tissue (protein specific)
EC Number
Source Tissue
Commentary
Organism
Textmining
1.1.1.188
lung
-
Homo sapiens
-
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
1.1.1.188
additional information
the enzyme has dual activity as PGD2 11-ketoreductase and PGH2 9,11-endoperoxide reductase
667713
Homo sapiens
?
-
-
-
-
1.1.1.188
additional information
PGFS does not catalyze the reduction of prostaglandin E2
667713
Homo sapiens
?
-
-
-
-
1.1.1.188
prostaglandin D2 + NADPH
-
667713
Homo sapiens
9alpha,11beta-prostaglandin F2alphabeta + NADP+
-
-
-
?
1.1.1.188
prostaglandin D2 + NADPH + H+
-
667713
Homo sapiens
prostaglandin 9alpha,11beta-F2 + NADP+
-
-
-
-
1.1.1.188
prostaglandin H2 + NADPH
-
667713
Homo sapiens
9alpha,11alpha-prostaglandin F2alpha + NADP+
-
-
-
?
1.1.1.188
prostaglandin H2 + NADPH + H+
-
667713
Homo sapiens
prostaglandin F2alpha + NADP+
-
-
-
?
Temperature Optimum [C] (protein specific)
EC Number
Temperature Optimum [C]
Temperature Optimum Maximum [C]
Commentary
Organism
1.1.1.188
30
-
assay at, PGH2 9,11-endoperoxide reductase activity
Homo sapiens
1.1.1.188
37
-
assay at, PGD2 11-ketoreductase activity
Homo sapiens
pH Optimum (protein specific)
EC Number
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
1.1.1.188
6.5
-
assay at, PGD2 11-ketoreductase activity and PGH2 9,11-endoperoxide reductase activity
Homo sapiens