Structural biology of MD-2 and TLR4 protein toward a therapeutic drug for sepsis

• Project/Area Number: 19890048
• Research Category: Grant-in-Aid for Young Scientists (Start-up)
• Allocation Type: Single-year Grants
• Research Field: Physical pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: OHTO Umeharu The University of Tokyo, 大学院・薬学系研究科, 助教 (90451856)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,125,000 (Direct Cost: ¥2,720,000、Indirect Cost: ¥405,000); Fiscal Year 2008: ¥1,755,000 (Direct Cost: ¥1,350,000、Indirect Cost: ¥405,000); Fiscal Year 2007: ¥1,370,000 (Direct Cost: ¥1,370,000)
• Keywords: 結晶構造解析 / 自然免疫 / エンドトキシン / リポ多糖 / 構造生物学

Research Abstract

エンドトキシンであるLPSの細胞外受容体を構成する蛋白質ヒトMD-2単体の三次元構造とアンタゴニストであるlipid IVaの複合体の三次元構造を解析した。MD-2には大きな疎水的ポケットが存在すること, lipid IVaはその疎水的ポケットに結合することから, MD-2 がLPS認識において中心的な役割を担うことを明らかとした。

Research Products

• [Journal Article] Crystal twinning of human MD-2 protein recognizing endotoxin cores of lipopolysaccharide (2008)
  • Author(s): Ohto, U. and Satow, Y.
  • Journal Title: J. Synchrotron. Radiat 15 Pages: 262-265
  • Peer Reviewed
• [Journal Article] Crystal twinning of human MD-2 protein recognizing endotoxin cores of lipopo lysaccharide (2008)
  • Author(s): Ohto, U. and Satow, Y.
  • Journal Title: J. Synchrotron. Radiat. 15 Pages: 262-265
  • Peer Reviewed
• [Journal Article] Crystal structures of human MD-2 and its complex with antiendotoxic lipid Iva (2007)
  • Author(s): Ohto, U., Fukase, K., Miyake, K., and Satow,Y
  • Journal Title: Science 316 Pages: 1632-1634
  • Peer Reviewed
• [Journal Article] Crystal structures of human MD-2 and its complex with antiendotoxiclipid IVa (2007)
  • Author(s): Ohto, U., Fukase, K., Miyake, K., and Satow, Y.
  • Journal Title: Science 316 Pages: 1632-1634
  • Peer Reviewed
• [Presentation] Crystal structures of human MD-2 recognizing bacterial endotoxin (2007)
  • Author(s): Ohto, U. and Satow, Y
  • Organizer: Biochemistry and molecular Biology 2007
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] Crystal twinning of human MD-2 protein recognizing endotoxin cores oflipopolysaccharide (2007)
  • Author(s): Ohto, U. and Satow, Y
  • Organizer: International symposium on diffraction structural biology 2007
  • Place of Presentation: 東京
  • Year and Date: 2007-09-12
• [Remarks]
  • URL: http://www.f.u-tokyo.ac.jp/~shomu/old_news.html