Crystal structure determination of microsomal prostaglandin E2 synthase 1 with the open active site.

• Project/Area Number: 23570153
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: AGO Hideo 独立行政法人理化学研究所, 放射光科学総合研究センター, 専任研究員 (70360477)
• Co-Investigator(Renkei-kenkyūsha): SAINO Hiromichi 青山学院大学, 理工学部, 助教 (40525549)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 膜タンパク質 / Ｘ線結晶構造解析 / 結晶化 / 界面活性剤 / ロイコトリエン / X線結晶構造解析 / 炎症 / 脂質

Research Abstract

Human membrane protein MPGES1, which is a responsible protein for biosynthesis of prostaglandin E2 as a proinflammatory lipid mediator, was crystallized in a lipidic meso crystallization method. MPGES1 in the lipidic meso phase could be a structure more similar to a structure in cell membrane due to the similarity between the structures of the lipidic meso phase and cell membrane. The inhibitors for MPGES1 were found out from the candidates from the in silico screening targeted to the active site of leukotriene C4 synthase belonging in the same protein family with MPGES1. These results will contribute the elucidation of the structure basis of molecular functions of MPGES1.

Research Products

• [Journal Article] A leukotriene C4 synthase inhibitor with the backbone of 5-(5-methylene-4-oxo-4,5-dihydrothiazol-2-ylamino) isophthalic acid (2013)
  • Author(s): Ago, H. Okimoto, N. Kanaoka, Y. Morimoto, G. Ukita, Y. Saino, H. Taiji, M. Miyano, M.
  • Journal Title: journal of biochemistry Volume: in press Issue: 5 Pages: 421-429
  • DOI: 10.1093/jb/mvt007
  • Peer Reviewed
• [Journal Article] The Catalytic Architecture of Leukotriene C4 Synthase with Two Arginine Residues (2011)
  • Author(s): Saino, Hiromichi Ukita, Yoko Ago, Hideo Irikura, Daisuke Nisawa, Atsushi Ueno, Go Yamamoto, Masaki Kanaoka, Yoshihide Lam, Bing K. Austen, K. Frank Miyano, Masashi
  • Journal Title: Journal of Biological Chemistry Volume: 286 Pages: 16392-16401
  • Peer Reviewed
• [Journal Article] Seleno-detergent MAD phasing of leukotriene C4 synthase in complex with dodecyl-β-D-selenomaltoside. (2011)
  • Author(s): Saino Hiromichi, Ago Hideo, Ukita Yoko, Miyano Masashi.
  • Journal Title: Acta Crystallogr Sect F Struct Biol Cryst Commun. Volume: 67 Pages: 1666-1673
  • Peer Reviewed
• [Presentation] X-ray protein crystallography free from radiation damage at SACLA (2012)
  • Author(s): Ago, H.
  • Organizer: The Sagamore XVII
  • Place of Presentation: Date, Hokkaido
  • Year and Date: 2012-07-19