Structural Characterization of Heme-mediated Signaling Mechanism in Protein Regulation System

• Project/Area Number: 21370040
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Hokkaido University
• Principal Investigator: ISHIMORI Koichiro 北海道大学, 大学院・理学研究院, 教授 (20192487)
• Co-Investigator(Kenkyū-buntansha): UCHIDA Takeshi 北海道大学, 大学院・理学研究院, 助教 (30343742)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2011: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2010: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2009: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
• Keywords: ヘム依存性制御蛋白質 / 酸化修飾 / 活性酸素 / ヘム生合成 / 鉄代謝

Research Abstract

In this research project, we characterized the heme binding in Iron Response Regulator (Irr) and Iron Regulatory Protein (IRP) and examined their functional significance. We spectroscopically identified the heme binding sites of Irr and, based on the structural information, a molecular mechanism of heme-induced oxidative modification in Irr was proposed. The heme binding sites of IRP were also determined and a new mechanism for the translational regulation by binding of heme was suggested in IRP. These new findings in this research project shed new light on the functional significance of heme in vivo.

Research Products

• [Journal Article] A Heme Degradation Enzyme, HutZ, fromVibrio cholera (2012)
  • Author(s): Uchida, T., Sekine, Y., Matsui, T., Ikeda-Saito, M., Ishimori, K.
  • Journal Title: Chem. Comm.
  • Peer Reviewed
• [Journal Article] Unusual Heme Binding in the Bacterial Iron Response Regulator Protein (Irr) : Spectral Characterization of Heme Binding to Heme Regulatory Motif (2011)
  • Author(s): Ishikawa, H., Nakagaki, M., Bamba, A., Uchida, T., Hori, H., O'Brian, M. R., Iwai, K., Ishimori, K.
  • Journal Title: Biochemistry Volume: 50(6) Pages: 1016-1022
  • Peer Reviewed
• [Journal Article] Unusual Heme Binding in the Bacterial Iron Response Regulator Protein (Irr) : Spectral Characterization of Heme Binding to Heme Regulatory Motif (2011)
  • Author(s): Ishikawa, H.
  • Journal Title: Biochemistry Volume: 50 Pages: 1016-1022
  • Peer Reviewed
• [Journal Article] Molecular Oxygen Regulates the Enzymatic Activity of a Heme-containing Diguanylate Cyclase (HemDGC) for the Synthesis of Cyclic di-GMP (2010)
  • Author(s): Sawai, H., Yoshioka, S., Uchida, T., Hyodo, M., Hayakawa, Y., Ishimori, K., Aono, S.
  • Journal Title: Biochim. Biophys. Acta Volume: 1804(1) Pages: 166-172
  • Peer Reviewed
• [Journal Article] Molecular Oxygen Regulates the Enzymatic Activity oF a Heme-containing Diguanylate Cyclase (HemDGC) for the Synthesis of Cyclic di-GMP (2010)
  • Author(s): Sawai, H.
  • Journal Title: Biochimca Biophysica Acta Volume: 1804 Pages: 166-172
  • Peer Reviewed
• [Journal Article] Molecular Oxygen Regulates the Enzymatic Activity of a Heme-containing Diguanylate Cyclase(HemDGC)for the Synthesis of Cyclic di-GMP (2010)
  • Author(s): Sawai, H., et al.
  • Journal Title: Biochim.Biophys.Acta 1804 Pages: 166-172
  • Peer Reviewed
• [Presentation] Function of Heme Regulatory Motif in the Oxidative Modification for Transcriptional Regulation (2011)
  • Author(s): Taira Tatsukawa
  • Organizer: 第48回ペプチド討論会
  • Place of Presentation: 札幌コンベンションセンター(札幌市)
  • Year and Date: 2011-09-27
• [Presentation] ヘムの結合による鉄代謝制御タンパク質IRPの機能制御機構 (2011)
  • Author(s): 石森浩一郎
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都国際会館(京都市)(招待講演)
  • Year and Date: 2011-09-21
• [Presentation] Oxygen Activation and Oxidative Modification in Heme-regulated Proteins (2011)
  • Author(s): Ishimori, K.
  • Organizer: 14th Asian Chemical Congress
  • Place of Presentation: Queen Sirikit National Convention Center, タイ国,バンコク市
  • Year and Date: 2011-09-06
• [Presentation] Oxygen Activation and Oxidative Modification in Heme-regulated Proteins (2011)
  • Author(s): 石森浩一郎
  • Organizer: 14th Asian Chemical Congress
  • Place of Presentation: Queen Sirikit National Convention Center(タイ国)(招待講演)
  • Year and Date: 2011-09-06
• [Presentation] 鉄代謝制御蛋白質(IRPs)の標的RNA結合における制御機構の検討 (2011)
  • Author(s): 渡辺祐太
  • Organizer: 第64回日本酸化ストレス学会学術集会
  • Place of Presentation: ルスツリゾート(留寿都村)
  • Year and Date: 2011-07-02
• [Presentation] 鉄代謝制御タンパク質IRP2の機能発現における酸化修飾機構 (2011)
  • Author(s): 宮地祐樹
  • Organizer: 第64回日本酸化ストレス学会学術集会
  • Place of Presentation: ルスツリゾート(留寿都村)
  • Year and Date: 2011-07-02
• [Presentation] Heffle-mediated Iron Regulation Mechanism (2011)
  • Author(s): 石森浩一郎
  • Organizer: 日本生化学会九州支部例会シンポジウム
  • Place of Presentation: 久留米医科大学(久留米市)(招待講演)
  • Year and Date: 2011-05-21
• [Presentation] Oxidative modification and its functional significance in heme-regulated protein (2010)
  • Author(s): Ishimori, K.
  • Organizer: Pacifichem 2010
  • Place of Presentation: ハワイコンベンションセンター,米国,ホノルル市
  • Year and Date: 2010-12-15
• [Presentation] Oxidative modification and its functional significance in heme-regulated protein (2010)
  • Author(s): Ishimori, K.
  • Organizer: Pacifichem 2010
  • Place of Presentation: 米国,ハワイ,ホノルル市 招待講演
  • Year and Date: 2010-12-15
• [Presentation] Iron Response Regulator Protein Is a Self-oxidative Oxidase-transcription Factor : A Mechanism for Heme-mediated Self-oxidation (2009)
  • Author(s): Ishimori, K.
  • Organizer: 14th International Conference on Biological Inorganic Chemistry(ICBIC14)
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2009-07-30
• [Presentation] Iron Response Regulator Protein Is a Self-oxidative Oxidase-transcription Factor : A Mechanism for Heme-mediated Self-oxidation (2009)
  • Author(s): Ishimori, K.
  • Organizer: 14^<th> International Conference on Biological Inorganic Chemistry(ICBIC14)
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2009-07-30
• [Book] Heme binding characteristics of mouse PER1, a transcriptional regulatory factor associated with circadian rhythms (2011)
  • Author(s): R. Nagata, M. Harada, K. Kitanishi, J. Igarashi, T. Uchida, K. Ishimori and T. Shimizu
  • Publisher: Nova Science Publishers
• [Remarks]
  • URL: http://wwwchem.sci.hokudai.ac.jp/~stchem/