Reaction Mechanism of Heme Detoxification Enzyme

• Project/Area Number: 22770141
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Functional biochemistry
• Research Institution: Osaka University
• Principal Investigator: ISHIKAWA Haruto 大阪大学, 大学院・理学研究科, 講師 (40551338)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 酵素の触媒機構 / ヘム / 蛋白質 / 酵素

Research Abstract

Free heme is a pro-oxidant and catalyzes the production of reactive oxygen species that is toxic to cells. Heme detoxification protein(HDP), potent in converting heme into an insoluble crystalline form called hemozoin(Hz), was found in the malaria parasite. We succeeded in the high-yield expression of recombinant HDP in E. coli. ESR and resonance Raman measurements for the HDP-heme complex revealed that a histidine residue binds heme.

Research Products

• [Journal Article] Protein dynamics of isolated chains of recombinant human hemoglobin elucidated by time-resolved resonance Raman spectroscopy (2012)
  • Author(s): Kenta Yamada, Haruto Ishikawa, Yasuhisa Mizutani
  • Journal Title: Journal of Physical Chemistry B Volume: Vol.116 Pages: 1992-1998
  • Peer Reviewed
• [Journal Article] Protein Dynamics of Isolated Chains of Recombinant Human Hemoglobin Elucidated by Time-resolved Resonance Raman Spectroscopy (2012)
  • Author(s): Kenta Yamada, Haruto Ishikawa, and Yasuhisa Mizutani
  • Journal Title: J. Phys. Chem. B Volume: 116 Issue: 6 Pages: 1992-1998
  • DOI: 10.1021/jp2114303
  • Peer Reviewed
• [Journal Article] Unusual heme binding in the bacterial iron response regulator protein : spectral characterization of heme binding to the heme binding motif (2011)
  • Author(s): Haruto Ishikawa, Megumi Nakagaki, Ai Bamba, Takeshi Uchida, Hiroshi Hori, Mark R. O' Brian, Kazuhiro Iwai, Koichiro Ishimori
  • Journal Title: Biochemistry Volume: Vol.50 Pages: 1016-1022
  • Peer Reviewed
• [Journal Article] Unusual heme binding in the bacterial iron response regulator protein : spectral characterization of heme binding to the heme binding motif (2011)
  • Author(s): Ishikawa, H., et al.
  • Journal Title: Biochemistry Volume: 50 Pages: 1016-1022
  • Peer Reviewed
• [Presentation] Molecular mechanism of heme detoxification in malaria-causing parasite, Gordon research conference (2012)
  • Author(s): Haruto Ishikawa, Keisuke Nakatani, Shigetoshi Aono, Yasuhisa Mizutani
  • Organizer: Metals in biology
  • Place of Presentation: Four points sheraton, California, USA
  • Year and Date: 2012-01-23
• [Presentation] Molecular Mechanism of Heme Detoxification in Maralia-causing Parasite (2012)
  • Author(s): Ishikawa, H., Nakatani, K., Aono, S., Mizutani, Y.
  • Organizer: Gordon Research Conference : Metals in Biology
  • Place of Presentation: フォーポイントジェラトン(ヴェンチュラ、アメリカ)
• [Presentation] ヘモゾイン形成過程におけるHeme Detoxification Proteinとヘムの相互作用 (2011)
  • Author(s): 中谷圭佑、石川春人、青野重利、水谷泰久
  • Organizer: 第38回生体分子科学討論会
  • Place of Presentation: 筑波大学大学会館
  • Year and Date: 2011-06-24
• [Presentation] Molecular mechanism of heme detoxification in malaria-causing parasite (2011)
  • Author(s): Haruto Ishikawa, Keisuke Nakatani, Shigetoshi Aono, Yasuhisa Mizutani
  • Organizer: 11th HFSP Awardees meeting
  • Place of Presentation: McGill University, Montreal, Canada
  • Year and Date: 2011-06-06
• [Presentation] Molecular Mechanism of Heme Detoxification in Malaria-causing Parasite (2011)
  • Author(s): Ishikawa, H., Nakatani, K., Aono, S., Mizutani, Y.
  • Organizer: 11th HFSP Awardees Meeting
  • Place of Presentation: マギル大学(モントリオール、カナダ)
• [Remarks]
  • URL: http://www.chem.sci.osaka-u.ac.jp/lab/mizutani/index-jp.html
• [Remarks]
  • URL: http://www.chem.sci.osaka-u.ac.jp/lab/mizutani/index-jp.html
• [Remarks]
  • URL: http://www.chem.sci.osaka-u.ac.jp/lab/mizutani/index-jp.html