Interaction of heme and nitric oxide with heme-regulated inhibitor (HRI)

• Project/Area Number: 19770099
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Functional biochemistry
• Research Institution: Tohoku University
• Principal Investigator: IGARASHI Jotaro Tohoku University, 多元物質科学研究所, 助教 (80375162)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,610,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥210,000); Fiscal Year 2008: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2007: ¥2,700,000 (Direct Cost: ¥2,700,000)
• Keywords: ヘム / 一酸化窒素 / 自己リン酸化 / S-ニトロシル化 / ヘム調節キナーゼ / ヘム制御モチーフ / CPモチーフ / 翻訳制御

Research Abstract

ヘム調節インヒビター(HRI)の分子レベルでの活性調節機構を明らかにするために、ヘム結合部位の同定、一酸化窒素によるS-ニトロシル化反応、自己リン酸化反応、及びドメイン間の相互作用を解析した。ヘムはヘム制御モチーフと呼ばれるCys-Proを含む配列に結合し、活性調節に重要であることがわかった。また、ヘム結合によりN末端ドメインとキナーゼドメイン間に相互作用が生じ、構造変化することが明らかになった。

Research Products

• [Journal Article] Elucidation of the herne-binding site of heme-regulated elF2α kinase (HRI) and the role of the regulatory motif in heme sensing by spectroscopic and catalytic studies of mutant proteins (2008)
  • Author(s): Igarashi, J., Murase, M., Iizuka, A., Pichierri, F., Martinkova, M. and Shimizu, T.
  • Journal Title: J. Biol. Chem. 283 Pages: 18782-18791
  • Peer Reviewed
• [Journal Article] Arg97 at the heme-distal side of the isolated heure-bound PAS domain of a heure-based oxygen sensor from Escherichia coli (EcDOS) plays critical roles in autoxidation and binding to gases, particularly O_2 (2008)
  • Author(s): Ishitsuka, Y., Araki, Y., Tanaka, A., Igarashi, J., Ito, O. and Shimizu, T.
  • Journal Title: Biochemistry 47 Pages: 8874-8884
  • Peer Reviewed
• [Journal Article] Heme-binding characteristics of the isolated PAS-A domain of mouse Per2, a transcriptional regulatory factor associated with circadian rhythms (2008)
  • Author(s): Kitanishi, K., Igarashi, J., Hayasaka, K., Hikage, N., Saiful, I., Yamauchi, S., Uchida, T., Ishimori, K. and Shimizu, T.
  • Journal Title: Biochemistry 47 Pages: 6157-6168
  • Peer Reviewed
• [Journal Article] ヘムが移動して機能する生体反応-ヘムの移動により機能する蛋白質・酵素の機能 (2008)
  • Author(s): 五十嵐城太郎、清水透
  • Journal Title: 化学 63 Pages: 66-67
• [Journal Article] The roles of thiolate-heme proteins, other than the P450 cytochromes, in the regulation of heme-sensor proteins (2008)
  • Author(s): Igarashi, J., Kitanishi, K., Martinkova, M., Murase, M., Iizuka, A. and Shimizu, T.
  • Journal Title: Acta Chim. Slov. 55 Pages: 67-74
  • Peer Reviewed
• [Journal Article] Elucidation of the heme-binding site of heme-regualted eIFa kinase (HRI) and the role of the regulatory motif in heme sensing by spectroscopic and catalytic studies of mutant proteins (2008)
  • Author(s): Jotaro Igarashi
  • Journal Title: Journal of Biological Chemistry 283 Pages: 18782-18791
  • Peer Reviewed
• [Journal Article] Arg97 at the heme-distal side of the isolated heme-bound PAS domain of a heme-based oxygen sensor from Escherichia coli (Ec DOS) plays cri tical roles in autoxidation and binding to gases, particularly O_2 (2008)
  • Author(s): Yukako Ishitsuka
  • Journal Title: Biochemistry 47 Pages: 8874-8884
  • Peer Reviewed
• [Journal Article] Heme-binding characteristics of the isolated PAS-A domain of mouse Pe r2, a transcriptional regulatory factor associated with circadian rhythms (2008)
  • Author(s): Kenichi Kitanishi
  • Journal Title: Biochemistry 47 Pages: 6157-6168
  • Peer Reviewed
• [Journal Article] ヘムの移動により機能する生体反応・ヘムセンサータンパク質・素とヘム輸送体 (2008)
  • Author(s): 五十嵐城太郎
  • Journal Title: 化学 63 Pages: 66-67
• [Journal Article] The role of thiolate-heme proteins, other than the P450 cytochromes, in regulation of heme-sensor proteins (2008)
  • Author(s): Jotaro Igarashi
  • Journal Title: Acta Chimica Slovenica 55 Pages: 67-74
  • Peer Reviewed
• [Journal Article] Eukaryotic initiation factor 2α kinase is a nitric oxide-responsive mercury sensor enzyme : potent inhibition of catalysis by the mercury cation and reversal by nitric oxide (2007)
  • Author(s): Martinkova, M., Igarashi, J. and Shimizu, T.
  • Journal Title: FEBS Lett. 581 Pages: 4109-4114
  • Peer Reviewed
• [Journal Article] Identification of Cys385 in the isolated kinase insertion domain of heme-regulated eIF2α kinase (HRI) as the heme axial ligand by site-directed mutagenesis and spectral characterization (2007)
  • Author(s): Hirai, K., Martinkova, M., Igarashi, J., Saiful, I., Yamauchi, S., El-Mashtoly, S. F., Kitagawa, T. and Shimizu, T.
  • Journal Title: J. Inorg. Biochem. 101 Pages: 1172-1179
  • Peer Reviewed
• [Journal Article] ドメイン間相互作用による酵素活性の制御 (2007)
  • Author(s): 五十嵐城太郎、田中敦成、清水透
  • Journal Title: 生体の科学 58 Pages: 354-356
• [Journal Article] Eukaryotic initiation factor 2α kinase is a nitric oxide-responsive mercury sensor enzyme: Potent inhibition of catalysis by the mercury cation and reversal by nitric oxide (2007)
  • Author(s): Marketa Martinkova
  • Journal Title: FEBS Letters 581 Pages: 4109-4114
  • Peer Reviewed
• [Journal Article] Identification of Cys385 in the isolated kinase insertion domain of heme-regulated eIF2α kinase (HRI) as the heme axial ligand by site-directed mutagenesis and spectral characterization (2007)
  • Author(s): Kyoko Hirai
  • Journal Title: Journal of Inorganic Biochemistry 101 Pages: 1172-1179
  • Peer Reviewed
• [Journal Article] ドメイン間相互作用による酵素活性の制御 (2007)
  • Author(s): 五十嵐 城太郎
  • Journal Title: 生体の科学 58 Pages: 354-356
• [Presentation] Identification of the heme axial ligand of HRI : Role of heme regulator motifs (2008)
  • Author(s): Jotaro Igarashi, Motohiko Murase, Toru Shimizu
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会BMB2008
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] Identification of the heme axial ligand of HRI : Role of heme regulator motifs (2008)
  • Author(s): Jotaro Igarashi
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] Elucidation of the heme-binding site of heme-regualted eIF2α kinase (HRI) and the role of the regulatory motif in heme sensing by spectroscopic and catalytic studies of mutant proteins (2008)
  • Author(s): Jotaro Igarashi, Motohiko Murase, Aya Iizuka, Fabio Pichierri, Marketa Martinkova, Toru Shimizu
  • Organizer: Gordon Research Conference on the Chemistry and Biology of Tetrapyrroles
  • Place of Presentation: Newport, RI, U. S. A.
• [Presentation] Elucidation of the heme-binding site of heme-regualted eIF2a kinase (H RI) and the role of the regulatory motif in heme sensing by spectroscop ic and catalytic studies of mutant proteins (2008)
  • Author(s): Jotaro Igarashi
  • Organizer: Gordon Research Conference on the Chemistry an d Biology of Tetrapyrroles
  • Place of Presentation: Newport, RI, USA
• [Presentation] Oxygen stability and crystal structure of Tetrahymena truncated hemoglobin (2007)
  • Author(s): Jotaro Igarashi, Ariki Matsuoka, Tom Shimizu
  • Organizer: 日本生物物理学会第45回年会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-23
• [Presentation] Oxygen stability and crystal structure of Tetrahymena truncated hemoglobin (2007)
  • Author(s): 五十嵐 城太郎
  • Organizer: 日本生物物理学会第45回年会
  • Place of Presentation: パシフィコ横浜、横浜
  • Year and Date: 2007-12-23
• [Presentation] Identification of the heme axial ligand, Cys, of HRI : Role of heme regulatory motifs (2007)
  • Author(s): Jotaro Igarashi, Motohiko Murase, Aya Iizuka, Marketa Miksanova, Toru Shimizu
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会BMB2007
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-11
• [Presentation] Identification of the heme axial ligand, Cys, of HRI: Role of heme regulatory motifs (2007)
  • Author(s): 五十嵐 城太郎
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会 合同大会
  • Place of Presentation: パシフィコ横浜、横浜
  • Year and Date: 2007-12-11
• [Presentation] Identification of a heme axial ligand of heme-regulated eukaryotic initiation factor 2α kinase (HRI) : Role of the Cys-Pro motif in heme regulation (2007)
  • Author(s): Jotaro Igarashi, Aya Iizuka, Motohiko Murase, Marketa Martinkova, Toru Shimizu
  • Organizer: 13th International Conference on Biological Inorganic Chemistry
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2007-07-17
• [Presentation] Identification of a heme axial ligand of heme-regulated eukaryotic initiation factor 2 alpha kinase (HRI): Role of the Cys-Pro motif in heme regulation (2007)
  • Author(s): Jotaro Igarashi
  • Organizer: 13th International Conference on Biological Inorganic Chemistry
  • Place of Presentation: ウィーン、オーストリア
  • Year and Date: 2007-07-17
• [Remarks]
  • URL: http://www.tagen.tohoku.ac.jp/labo/shimizu/
• [Remarks]
  • URL: http://db.tohoku.ac.jp/whois/Tunv_Title_All.php?&user_num=z8/Pz8/Pz8/Mz8zH&sell=1&sel2=1&sel3=1&sel4=0&page=1&lang=J
• [Remarks]
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• [Remarks]
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