Identification and biological functions of lipid mediator binding proteins
Project/Area Number |
16K08596
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
General medical chemistry
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Research Institution | Juntendo University |
Principal Investigator |
OKUNO TOSHIAKI 順天堂大学, 医学(系)研究科(研究院), 准教授 (60361466)
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Project Period (FY) |
2016-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | GPCR / 脂質メディエーター / インバースアゴニスト / BLT1 / ロイコトリエンB4 / LTB4 / 構造活性相関 / 脂質 / ロイコトリエン / 立体構造解析 / 脂質生化学 / ケミカルバイオロジー / 生体分子 / 生理活性 |
Outline of Final Research Achievements |
BLT1 is a high affinity G-protein coupled receptor (GPCR) for leukotriene B4 (LTB4) and involved in the activation and chemotaxis of leukocytes. In this study, we succeeded in the structural analysis of the complex of BLT1 and the inverse agonist, BIIL260. The benzamidine moiety of BIIL260 bound to the binding pocket of the sodium ion and water cluster and stabilized the inactivate state of GPCR. As the residues involved in the benzamidine binding are widely conserved among many GPCRs, the present structure will enable the rational development of inverse agonists specific for each GPCR.
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Academic Significance and Societal Importance of the Research Achievements |
Gタンパク質共役型受容体(GPCR)は、哺乳類において最大の遺伝子ファミリーを形成し、現在用いられている薬剤の3分の1がGPCRを標的としている。したがって、GPCRの活性を抑制する拮抗薬(インバースアゴニスト)の開発は創薬に直結する。本研究によって、GPCRの拮抗薬を理論的に設計することが可能となり、GPCRを標的とした創薬研究が飛躍的に進展することが期待される。
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Report
(5 results)
Research Products
(67 results)
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[Journal Article] Prostaglandin E2 and its receptor EP2 trigger signaling that contributes to YAP-mediated cell competition.2020
Author(s)
Ishihara E, Nagaoka Y, Okuno T, Kofuji S, Ishigami-Yuasa M, Kagechika H, Kamimura K, Terai S, Yokomizo T, Sugimoto Y, Fujita Y, Suzuki A, Nishina H.
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Journal Title
FASEB J
Volume: 25(3)
Pages: 14528-14541
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Leukotriene B4 promotes neovascularization and macrophage recruitment in murine wet-type AMD models.2018
Author(s)
Sasaki F., Koga T., Ohba M., Saeki K., Okuno T., Ishikawa K., Nakama T., Nakao S., Yoshida S., Ishibashi T., Ahmadieh H., Kanavi M. R., Hafezi-Moghadam A., Penninger J. M., Sonoda K. H., Yokomizo T.
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Journal Title
JCI Insight
Volume: 3
Pages: 96902-96902
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Intravenous anesthetic propofol binds to 5-lipoxygenase and attenuates leukotriene B4 production2017
Author(s)
Okuno, T., Koutsogiannaki, S., Ohba, M., Chamberlain, M., Bu, W., Lin, F. Y., Eckenhoff, R. G., Yokomizo, T.,Yuki, K.
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Journal Title
The FASEB Journal
Volume: 31
Pages: 1584-1594
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Leukotriene B4 receptor type 2 protects against pneumolysin-dependent acute lung injury2017
Author(s)
Shigematsu, M., Koga, T., Ishimori, A., Saeki, K., Ishii, Y., Taketomi, Y., Ohba, M., Jo-Watanabe, A., Okuno, T., Harada, N., Harayama, T., Shindou, H., Li, J. D., Murakami, M., Hoka, S.,Yokomizo, T.
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Journal Title
Scientific Reports
Volume: 6
Pages: 34560-34560
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Prolonged exposure to volatile anesthetic isoflurane worsens the outcome of polymicrobial abdominal sepsis2017
Author(s)
Koutsogiannaki, S., Schaefers, M. M., Okuno, T., Ohba, M., Yokomizo, T., Priebe, G. P., DiNardo, J. A., Sulpicio, S. G.,Yuki, K.
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Journal Title
Toxicol Sci
Volume: in press
Pages: 402-411
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] Deficiency of BLT1, the high-affinity receptor for LTB4, alleviates allergic conjunctivitis in mice. 60th ICBL2019
Author(s)
Hirakata T., Lee C. H., Yasukawa K., Adachi K., Saeki K., Okuno T., Murakami A., Matsuda A., Yokomizo T..
Organizer
International Conference on the Bioscience of Lipids
Related Report
Int'l Joint Research
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