Prostaglandin D synthase

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Function

Prostaglandin D synthase (PGDS) catalyzes the reversible conversion of 9α-11α-epidoxy-15-hydroxyprosta-5,13-dienoate to 9α-15-dihydroxy-11-oxoprosta-5,13-dienoate. Prostaglandin D2 synthase (PGD2S) catalyzes the conversion of prostaglandin H2 to prostaglandin D2 (PGD2). PGD2 functions as a neuromodulator in smooth muscle contraction. Human PGD2S has two isozymes: hematopoietic PGD2S found in mast cells see Glutathione S-transferase σ which is glutathione-dependent and lipocalin PGD2S found in the central nervous system, genital organs and heart. This enzyme is glutathione-independent and transports small hydrophobic molecules such as steroids. PGDS is a major constituent of cerebrospinal fluid. PGDS binds small lipophilic molecules like retinal and thyroid hormone[1].

Relevance

PGDS is believed to be a cause of baldness[2]. PGD2S inhibitors are tested as potential anti-inflammation and anti-allergic drugs.

Structural highlights

  • Thiocyanate binding site.
  • 1st Cl coordination site. Water molecule is shown as red sphere.
  • 2nd Cl coordination site.

Human lipocalin prostaglandin D synthase complex with thiocyanate and Cl- ion (green) (PDB entry 2wwp)

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3D structures of prostaglandin D synthase

Updated on 13-September-2023

Hematopoietic PGD2S (Glutathione-dependent) or HGTS1 see Glutathione S-transferase σ

References

  1. Urade Y, Hayaishi O. Prostaglandin D synthase: structure and function. Vitam Horm. 2000;58:89-120. PMID:10668396
  2. Garza LA, Liu Y, Yang Z, Alagesan B, Lawson JA, Norberg SM, Loy DE, Zhao T, Blatt HB, Stanton DC, Carrasco L, Ahluwalia G, Fischer SM, FitzGerald GA, Cotsarelis G. Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia. Sci Transl Med. 2012 Mar 21;4(126):126ra34. doi: 10.1126/scitranslmed.3003122. PMID:22440736 doi:http://dx.doi.org/10.1126/scitranslmed.3003122

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