New Aspects on Prostaglandin D Synthases

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Prostaglandin (PG) D2 is a major prostanoid produced in the central nervous system and mast cells, acting as a neuromodulator and an allergic and inflammatory mediator. PGD2 is readily dehydrated to produce PGs of the J series, such as PGJ2, Δ12-PGJ2, and 15-deoxy-Δ12, 14-PGJ2. We identified two distinct types of PGD synthase: one is glutathione independent, the lipocalin-type enzyme; and the other is glutathione-dependent, the hematopoietic enzyme. Lipocalin-type PGD synthase is localized in the central nervous sytem and genital organs, dominantly produced in the leptomeninges of the brain and pigmented epithelium of the retina, and is actively secreted as β-trace into the cerebrospinal fluid and interphotoreceptor matrix, respectively. Since the enzyme binds all-trans or 9-cis-retinoic acid with Kd of about 100 nM, it is considered to be a bifuncxional protein acting as a PGD2-producing enzyme and an extracellular retinoid-transporter. Alternatively, we recently cloned the cDNA for hematopoietic PGD synthase, crystallized the recombinant enzyme, and determined the three-dimensional structure. The enzyme is the first member of the sigma class glutathione S-transferase (GST) from vertebrates and possesses a prominent cleft as the active site, which is never seen among other members of the GST family.
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