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Literature summary for 1.1.1.188 extracted from

  • Komoto, J.; Yamada, T.; Watanabe, K.; Woodward, D.F.; Takusagawa, F.
    Prostaglandin F2alpha formation from prostaglandin H2 by prostaglandin F synthase (PGFS): crystal structure of PGFS containing bimatoprost (2006), Biochemistry, 45, 1987-1996.
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
expressed in Escherichia coli HB101 cells Homo sapiens
expression in Escherichia coli strain HB101 Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
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
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, 4°C, 14 days, thick plate-shaped crystals, X-ray diffraction structure determination and analysis at 2.0 A resolution Homo sapiens

Protein Variants

Protein Variants Comment Organism
Y55F site-directed mutagenesis, the mutant loses its PGD2 11-ketoreductase activity, but not the PGH2 9,11-endoperoxide reductase Homo sapiens
Y55F the mutated enzyme loses the prostaglandin D2 11-ketoreductase activity but retains the prostaglandin H2 9,-11-endoperoxide reductase activity Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
9,10-phenanthrenequinone the prostaglandin D2 11-ketoreductase activity of PGFS is competitively inhibited by 9,10-phenanthrenequinone Homo sapiens
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)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens the enzyme has dual activity as PGD2 11-ketoreductase and PGH2 9,11-endoperoxide reductase ?
-
?
prostaglandin D2 + NADPH + H+ Homo sapiens
-
9alpha,11beta-prostaglandin F2alphabeta + NADP+
-
?
prostaglandin H2 + NADPH + H+ Homo sapiens
-
9alpha,11alpha-prostaglandin F2alpha + NADP+
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Homo sapiens P42330
-
-

Purification (Commentary)

Purification (Comment) Organism
-
Homo sapiens
recombinant enzyme from Escherichia coli strain HB101 to homogeneity Homo sapiens

Reaction

Reaction Comment Organism Reaction ID
(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

Source Tissue Comment Organism Textmining
lung
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information the enzyme has dual activity as PGD2 11-ketoreductase and PGH2 9,11-endoperoxide reductase Homo sapiens ?
-
?
additional information PGFS does not catalyze the reduction of prostaglandin E2 Homo sapiens ?
-
?
prostaglandin D2 + NADPH + H+
-
Homo sapiens prostaglandin 9alpha,11beta-F2 + NADP+
-
?
prostaglandin D2 + NADPH + H+
-
Homo sapiens 9alpha,11beta-prostaglandin F2alphabeta + NADP+
-
?
prostaglandin H2 + NADPH + H+
-
Homo sapiens prostaglandin F2alpha + NADP+
-
?
prostaglandin H2 + NADPH + H+
-
Homo sapiens 9alpha,11alpha-prostaglandin F2alpha + NADP+
-
?

Synonyms

Synonyms Comment Organism
PGD2 11-ketoreductase
-
Homo sapiens
PGFS
-
Homo sapiens
PGH2 9,11-endoperoxide reductase
-
Homo sapiens
prostaglandin F synthase
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
30
-
assay at, PGH2 9,11-endoperoxide reductase activity Homo sapiens
37
-
assay at, PGD2 11-ketoreductase activity Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
6.5
-
assay at, PGD2 11-ketoreductase activity and PGH2 9,11-endoperoxide reductase activity Homo sapiens

Cofactor

Cofactor Comment Organism Structure
NADPH
-
Homo sapiens