Structure determination of histamine H1 receptor

• Project/Area Number: 24370044
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Kyoto University
• Principal Investigator: SHIMAMURA Tatsuro 京都大学, 医学(系)研究科(研究院), 講師 (90391979)
• Co-Investigator(Kenkyū-buntansha): HINO Tomoya 鳥取大学, 大学院工学研究科, 講師 (40373360)
• Co-Investigator(Renkei-kenkyūsha): IWATA So 京都大学, 大学院医学研究科, 教授 (60452330) ; ASADA Hidetsugu 京都大学, 大学院医学研究科, 研究員 (20399041) ; OGASAWARA Satoshi 京都大学, 大学院医学研究科, 研究員 (30546685)
• Research Collaborator: LEURS Rob
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000); Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2013: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2012: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: アレルギー / 花粉症 / GPCR / 結晶構造解析 / ヒスタミン

Outline of Final Research Achievements

Antihistamines are inverse agonists of histamine H1 receptor and work well to relieve symptoms of allergies including pollen fever. Antihistamines are known to show undesirable side effects caused by the low receptor selectivity and the high ability to cross the blood-brain barrier. We succeeded to crystallize histamine H1 receptor in complex with the second-generation antihistamines. The structural information of these complexes would be useful for the development of new generation antihistamines without side effects.

Research Products

• [Journal Article] Grease matrix as a versatile carrier of proteins for serial crystallography. (2015)
  • Author(s): Sugahara M, Shimamura T, et al.
  • Journal Title: Nat Methods. Volume: 12 Issue: 1 Pages: 61-63
  • DOI: 10.1038/nmeth.3172
  • NAID: 120005682565
  • Peer Reviewed
• [Journal Article] Diverse application platform for hard X-ray diffraction in SACLA (DAPHNIS): application to serial protein crystallography using an X-ray free-electron laser. (2015)
  • Author(s): Tono K, Shimamura T, et al.
  • Journal Title: J. Synchrotron Rad. Volume: 22 Issue: 3 Pages: 532-537
  • DOI: 10.1107/s1600577515004464
  • Peer Reviewed
• [Journal Article] Proteoliposome-based selection of a recombinant antibody fragment against the human M2 muscarinic acetylcholine receptor. (2014)
  • Author(s): Suharni, Nomura Y, Arakawa T, Hino T, Abe H, Nakada-Nakura Y, Sato Y, Iwanari H, Shiroishi M, Asada H, Shimamura T, Murata T, Kobayashi T, Hamakubo T, Iwata S, Nomura N.
  • Journal Title: Monoclon Antib Immunodiagn Immunother Volume: 33 Issue: 6 Pages: 378-385
  • DOI: 10.1089/mab.2014.0041
  • NAID: 120005530933
  • Peer Reviewed
• [Journal Article] Crystal structure of a symmetric football-shaped GroEL:GroES2-ATP14 complex determined at 3.8Å reveals rearrangement between two GroEL rings. (2014)
  • Author(s): Koike-Takeshita A, Arakawa T, Taguchi H, Shimamura T.
  • Journal Title: J Mol Biol. Volume: 426 Issue: 21 Pages: 3634-41
  • DOI: 10.1016/j.jmb.2014.08.017
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] X-ray structure of histamine H1 receptor (2014)
  • Author(s): Shimamura T.
  • Journal Title: Nihon Yakurigaku Zasshi. Volume: 144 Pages: 43-4
  • NAID: 130004437205
• [Journal Article] ヒスタミンH１受容体の構造 (2014)
  • Author(s): 島村達郎
  • Journal Title: 日本薬理学会誌 Volume: 未定
  • NAID: 130004437205
• [Journal Article] ヒスタミン受容体 (2013)
  • Author(s): 島村達郎
  • Journal Title: 膜タンパク質構造研究 Volume: １ Pages: 11-18
  • Peer Reviewed
• [Journal Article] Generation of functional antibodies for mammalian membrane protein crystallography. (2013)
  • Author(s): Hino T, Iwata S, Murata T.
  • Journal Title: Curr Opin Struct Biol. Volume: 23 Issue: 4 Pages: 563-568
  • DOI: 10.1016/j.sbi.2013.04.007
  • Peer Reviewed
• [Journal Article] Platform for the rapid construction and evaluation of GPCRs for crystallography in Saccharoroyces cerevisiae. (2012)
  • Author(s): Shiroishi M., et al.
  • Journal Title: Micorb, Cell Fact. Volume: 11 Issue: 1 Pages: 78-78
  • DOI: 10.1186/1475-2859-11-78
  • Peer Reviewed
• [Journal Article] Conformational transition of the lid helix covering the protease active site is essential for the ATP-dependent protease activity of FtsH. (2012)
  • Author(s): Suno R. et al.
  • Journal Title: FEBS Lett Volume: 586 Issue: 19 Pages: 3117-21
  • DOI: 10.1016/j.febslet.2012.07.069
  • Peer Reviewed
• [Journal Article] Structure of histamine H1 receptor. (2012)
  • Author(s): Shimamura T.
  • Journal Title: Seikagaku. Volume: 84 Pages: 772-776
  • NAID: 10031122382
• [Journal Article] Structural biology and molecular targets. (2012)
  • Author(s): Shimamura T., Iwata S.
  • Journal Title: Nihon Rinsho. Volume: 70 Pages: 316-320
• [Journal Article] The Na+-hydantoin membrane transport protein, Mhp1. (2012)
  • Author(s): Jackson SM., et al.
  • Journal Title: Encyclopedia of Biophysics Pages: 1514-1521
• [Journal Article] 創薬ターゲット膜蛋白質の立体構造解析 (2012)
  • Author(s): 島村達郎、小笠原諭、岩田想
  • Journal Title: 内分泌・糖尿病・代謝内科 Volume: 35 Pages: 557-564
• [Presentation] ヒスタミンH1受容体の構造解析とin silico screening (2014)
  • Author(s): 島村達郎
  • Organizer: 日本内分泌学会学術総会
  • Place of Presentation: 博多
  • Year and Date: 2014-04-25
  • Invited
• [Presentation] ヒスタミンH1 受容体の構造解析とin silico screening (2014)
  • Author(s): 島村達郎
  • Organizer: 第８７回日本内分泌学会学術総会
  • Place of Presentation: 博多
• [Presentation] Crystal structure of Histamine H1 receptor and drug design. (2013)
  • Author(s): Shimamura T
  • Organizer: The 11th International Symposium for Future Drug Discovery and Medical Care.
  • Place of Presentation: Sapporo
  • Invited
• [Presentation] ヒスタミンH1受容体の構造により解明された抗ヒスタミン薬選択性機構 (2012)
  • Author(s): 島村達郎
  • Organizer: 第34回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 京都(招待講演)
  • Year and Date: 2012-11-15
• [Presentation] キュービックフェーズ法による膜タンパク質の結晶化 (2012)
  • Author(s): 島村達郎
  • Organizer: 蛋白研セミナー
  • Place of Presentation: 大阪(招待講演)
  • Year and Date: 2012-09-21
• [Presentation] 膜蛋白質の結晶化 (2012)
  • Author(s): 島村達郎
  • Organizer: 第12回 日本蛋白質科学会
  • Place of Presentation: 名古屋(招待講演)
  • Year and Date: 2012-06-20
• [Presentation] ヒト由来ヒスタミンH1受容体の立体構造 (2012)
  • Author(s): 島村達郎
  • Organizer: 第9回 GPCR研究会
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2012-05-11