Differential analysis of the crystal structures of active / inactive orexin receptor contributing to rational development of sleep control drug
Project/Area Number |
15K08268
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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 | Kyoto University |
Principal Investigator |
Suno Ryoji 京都大学, 医学研究科, 特定助教 (60447521)
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Co-Investigator(Kenkyū-buntansha) |
野村 紀通 京都大学, 医学研究科, 助教 (10314246)
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Co-Investigator(Renkei-kenkyūsha) |
KOBAYASHI Takuya 京都大学, 医学研究科, 准教授 (20311730)
Yanagisawa Masashi 筑波大学, 国際統合睡眠医科学研究機構, 教授 (20202369)
Saitoh Tsuyoshi 筑波大学, 国際統合睡眠医科学研究機構, 助教 (80609933)
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Research Collaborator |
Kobilka Brian K スタンフォード大学, 医学部, 教授
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Project Period (FY) |
2015-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Keywords | ヒト膜受容体 / GPCR / シグナル伝達 / X線結晶構造解析 / 抗体 / 薬剤開発 / ナルコレプシー / 睡眠 / 機能性抗体 / 膜タンパク質 / 創薬 |
Outline of Final Research Achievements |
Our goal is to determine the active and inactive crystal structures of OX1R and OX2R. We determined the structure of the selective antagonist EMPA-bound OX2R, and revealed the molecular mechanism of the selectivity of EMPA in detail. As the three-dimensional structure of OX1R and OX2R became clear, it was possible to provide useful information for drug development based on structural information. In addition, various tertiary structure-recognizing antibodies can be obtained during the research period, and one of them has been a functional antibody that inhibits signal transduction up to now. In the future, structure determination of active OX2R is expected as a part of research aimed at developing therapeutic drug for narcolepsy.
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Report
(4 results)
Research Products
(13 results)
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[Presentation] High-resolution crystal structures of human orexin 2 receptor bound to a selective antagonist EMPA2016
Author(s)
Ryoji Suno, Kanako Terakado Kimura, Takanori Nakane, Kunio Hirata, Keitaro Yamashita, Junmei Wang, Takaaki Fujiwara, Yasuaki Yamanaka, Dohyun, Im, Shoichiro Horita, Hirokazu Tsujimoto, Maki S. Tawaramoto, Takatsugu Hirokawa, Masaki Yamamoto, Daniel M. Rosenbaum, So Iwata, Tatsuro Shimamura, and Takuya Kobayashi
Organizer
内藤カンファレンス
Place of Presentation
サッポロ シャトレーゼ ガトーキングダム
Year and Date
2016-10-04
Related Report
Int'l Joint Research
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