| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Research Abstract |
Lipocalin-type Prostaglandin D synthase (L-PGDS) catalyzes the isomerization of prostaglandin H2 (PGH2) to produce prostaglandin D2 (PGD2), which acts as a potent endogenous somnogen in the brain. A number of studies of L-PGDS, as a drug target for sleep disorders, have been reported in attempts to understand its catalytic mechanism, and several substrate recognition models of L-PGDS have been proposed. However, details of the mechanism by which L-PDGS recognizes its substrates and products are obscure, since essential information, such as its binding affinity and stoichiometry, of the interactions between L-PGDS and its substrates and products remains unclear. Therefore, we carried out ITC and NMR experiments to characterize the binding properties. The results of the ITC and NMR measurements revealed that both the substrate and the product bind to L-PGDS in a stoichiometry of 2 to 1 and two binding sites, namely a high and a low affinity binding site, are present.
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