Abstract
Prostaglandin (PG) D synthase (PGDS, EC 5.3.99.2) catalyzes the isomerization of PGH2, a common precursor of various prostanoids, to produce PGD2 in the presence of sulfhydryl compounds. PGD2 induces sleep [1], regulates nociception, inhibits platelet aggregation, acts as an allergic mediator [2], and is further converted to 9α, 11β-PGF2 or the J series of PGs, such as PGJ2, Δ12-PGJ2, and 15-deoxy-Δl2,14-PGJ2. 15-Deoxy-Δ12,14-PGJ2 is a ligand for PPARγ, a nuclear receptor involved in differentiation of adipocytes, macrophages, and monocytes. Two distinct types of PGDS have been identified; one is the lipocalin-type enzyme (L-PGDS); and the other, the hematopoietic enzyme (H-PGDS). For each enzyme, we isolated the cDNA and the gene, determined the X-ray crystallographic structure, tissue distribution profile, and the cellular localization in several animal species, and generated gene-knockout (KO) and human enzyme-overexpressing transgenic (TG) mice. Although L-PGDS and H-PGDS catalyze the same reaction, they are quite different from each other in terms of their catalytic properties, amino acid sequence, tertiary structure, evolutional origin, gene structure, chromosomal localization, cellular localization, tissue distribution, and also functional relevance, as summarized in Table 1. Therefore, we consider that L-PGDS and H-PGDS are a novel example of functional convergence. We have recently reviewed a part of these findings elsewhere [3,4].
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Urade, Y., Hayaishi, O. (2001). Structure and Function of Two Distinct Types of Prostaglandin D Synthase. In: Samuelsson, B., Paoletti, R., Folco, G.C., Granström, E., Nicosia, S. (eds) Advances in Prostaglandin and Leukotriene Research. Medical Science Symposia Series, vol 16. Springer, Dordrecht. https://doi.org/10.1007/978-94-015-9721-0_12
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DOI: https://doi.org/10.1007/978-94-015-9721-0_12
Publisher Name: Springer, Dordrecht
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