Oxygen carrying mechanism of hemoglobin : verification of trigger model by using proximal cavity mutant hemoglobin

• Project/Area Number: 19579002
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biophysics
• Research Institution: Kanazawa University
• Principal Investigator: AKI Yayoi Kanazawa University, 保健学系, 助教 (00452110)
• Project Period (FY): 2007 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥3,720,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2009: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2008: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2007: ¥1,900,000 (Direct Cost: ¥1,900,000)
• Keywords: ヘモグロビン / 酸素運搬機能 / 高次構造変化 / 引き金説 / 四次構造変化

Research Abstract

Many people believe that the trigger of the quaternary structural transition of hemoglobin (Hb) is the displacement of the proximal His, which is the only amino acid binding directly to the heme iron (trigger model). I inspected the model by synthesizing the recombinant Hbs, in which the proximal His is replaced with Gly in the α or β subunit, and then analyzing the conformational change and the oxygen carrying mechanism of these Hbs. I have suggested that the shift of the proximal His in the α subunit is the trigger of the structural transition of Hb, whereas one of the β subunit is not the trigger because the conformational change is partially observed in the recombinant Hb without the β proximal His.

Research Products

• [Journal Article] Differences in coordination states of substituted tyrosine residues and quaternary structures among hemoglobin M probed by resonance Raman spectroscopy (2010)
  • Author(s): Aki Y., Nagai M., Nagai Y., Imai K., Aki M., Sato A., Kubo M., Nagatomo S., Kitagawa T.
  • Journal Title: Journal of Biological Inorganic Chemistry 15 Pages: 147-158
  • Peer Reviewed
• [Journal Article] Differences in coordination states of substituted tyrosine residues and quaternary structures among hemoglobin M probed by resonance Raman spectroscopy (2010)
  • Author(s): Aki Y, Nagai M, Nagai Y, Imai K, Aki M, Sato A, Kubo M, Nagatomo S, Kitagawa T.
  • Journal Title: Journal of Biological Inorganic Chemistry 15 Pages: 147-158
  • Peer Reviewed
• [Journal Article] Effect of reversed heme orientation on circular dichoroism and cooperative oxygen binding of human adult hemoglobin (2008)
  • Author(s): Nagai, M., Nagai, Y., Aki, Y., Imai, K., Wada, Y., Nagatomo, S., Yamamoto, Y.
  • Journal Title: Biochemistry 47 Pages: 517-525
  • Peer Reviewed
• [Journal Article] Reduction in hemoglobin-oxygen affinity results in the improvement of exercise capacity in mice with chronic heart failure (2008)
  • Author(s): Watanabe T, Takeda T, Omiya S, Hikoso S, Yamaguchi O, Nakano Y, Higuchi Y, Nakai A, Abe Y, Aki-Jin Y, Taniike M, Mizote I, Matsumura Y, Shimizu T, Nishida K, Imai K, Hori M, Shirasawa T, Otsu K.
  • Journal Title: Journal of the American College of Cardiology 52 Pages: 779-786
  • Peer Reviewed
• [Journal Article] Effect of reversed heme orientation on circular dichoroism and cooperative oxygen binding of human adult hemoglobin (2008)
  • Author(s): Nagai, M., Nagai, Y., Aki, Y., Imai, K., Wada, Y., Nagatomo, S. & Yamamoto, Y.
  • Journal Title: Biochemistry 47 Pages: 517-525
  • Peer Reviewed
• [Journal Article] Oxygenation properties of extracellular giant hemoglobin from Oligobrachia mashikoi (2007)
  • Author(s): Aki, Y., Nakagawa, T., Nagai, M., Sasayama, Y., Fukumori, Y., Imai, K.
  • Journal Title: Biochemical and Biophysical Research Communications 360 Pages: 673-678
  • Peer Reviewed
• [Journal Article] Changes of near-UV CD spectra of human hemoglobin upon the R->T quaternary structure transition (2007)
  • Author(s): Aki-Jin Y., Nagai Y., Imai K., Nagai M.
  • Journal Title: ACS Symposium Book on "New Approaches in Biomedical Spectroscopy" 963 Pages: 297-311
  • Peer Reviewed
• [Journal Article] Oxygenation properties of extracellular giant hemoglobin from Oligobrachia mashikoi (2007)
  • Author(s): Aki, Y., Nakagawa, T., Nagai, M., Sasayama, Y., Fukumori, Y. & Imai, K
  • Journal Title: Biochemical and Bjophysical Research Communications 360 Pages: 673-678
  • Peer Reviewed
• [Journal Article] Changes of near-UV circular dichroism spectra of human hemoglobin upon the R→T quaternary structure transition (2007)
  • Author(s): Aki-Jin, Y., Nagai, Y., Imai, K. & Nagai, M
  • Journal Title: ACS Symposium Series on New Approaches in Biomedical Spectroscopy 963 Pages: 297-311
  • Peer Reviewed
• [Presentation] Coordination states of proximal or distal tyrosine residue in Hemoglobins M and their quaternary structures probed by resonance Raman spectroscopy (2009)
  • Author(s): Aki Y., Nagai M., Imai K., Aki M., Kitagawa T.
  • Organizer: 第47回日本生物物理学会年会
  • Place of Presentation: アスティとくしま(徳島県)
  • Year and Date: 2009-10-30
• [Presentation] Coordination states of proximal or distal tyrosine residue in Hemoglobins M and their quaternary structures probed by resonance Raman spectroscopy (2009)
  • Author(s): Aki Y., Nagai M., Imai K., Aki M., Kitagawa T.
  • Organizer: 第47回日本生物物理学会年会
  • Place of Presentation: アスティとくしま (徳島県)
  • Year and Date: 2009-10-30
• [Presentation] Differences in coordination states of replaced tyrosine residues and quaternary structures among hemoglobins M probed by resonance Raman Spectroscopy14th International Conference on Biological (2009)
  • Author(s): 長井幸史, 安藝弥生, 北川禎三
  • Organizer: Inorganic Chemistry
  • Place of Presentation: Nagoya Congress Center(愛知県)
  • Year and Date: 2009-07-26
• [Presentation] Differences in coordination states of replaced tyrosine residues and quaternary structures among hemoglobins M probed by resonance Raman spectroscopy (2009)
  • Author(s): Nagai M, Aki Y, Kitagawa T.
  • Organizer: 14th International Conference on Biological, Inorganic Chemistry
  • Place of Presentation: Nagoya Congress Center (愛知県)
  • Year and Date: 2009-07-26
• [Presentation] Differences in coordination states of replaced tyrosine residues and quaternary structures among hemoglobins M probed by resonance Raman spectroscopy (2009)
  • Author(s): 長井雅子, 安藝弥生, 北川禎三
  • Organizer: 14^<th> International Conference on Biological Inorganic Chemistry
  • Place of Presentation: Nagoya Congress Center (愛知県)
  • Year and Date: 2009-07-26
• [Presentation] ヘモグロビンの3つのトリプトファン残基の環境とその酸素結合による変化 : 近紫外円二色性及び紫外共鳴ラマン分光による研究 (2009)
  • Author(s): 長井雅子, 大久保賢一, 安藝弥生, 長井幸史, 今井清博, 長友重紀, 北川禎三
  • Organizer: 第36回生体分子科学討論会
  • Place of Presentation: 北海道大学学術交流会館 (北海道)
  • Year and Date: 2009-06-20
• [Presentation] Functional properties of mersalylmodified hemoglobin (2) (2008)
  • Author(s): Kuriyama, S., Aki, Y, Imai K.
  • Organizer: 第46回日本生物物理学会年会
  • Place of Presentation: 福岡国際会議場(福岡県)
  • Year and Date: 2008-12-03
• [Presentation] Functional properties of mersalyl-modified hemoglobin (2) (2008)
  • Author(s): Kuriyama, S., Aki, Y. Imal, K.
  • Organizer: 第46回日本生物物理学会牟会
  • Place of Presentation: 福岡国際会議場(福岡市)
  • Year and Date: 2008-12-03
• [Presentation] Environmental alterations of three tryptophan residues in human adult hemoglobin (Hb A) : A near-UV circular dichroism study (2008)
  • Author(s): Ohkubo, K., Aki, Y., Imai, K., Nagai, Y., Nagai, M.
  • Organizer: 第46回日本生物物理学会年会
  • Place of Presentation: 福岡国際会議場(福岡市)
  • Year and Date: 2008-12-03
• [Presentation] Environmental alterations of three tryptophan residues in human adult hemoglobin upon ligand binding (2008)
  • Author(s): 小久保昭秀, 安藝弥生, 今井清博, 長井雅子, 長井幸史
  • Organizer: XXI International Conference on Raman Spectroscopy ICORS 2008
  • Place of Presentation: Uxbridge (United Kingdom)
  • Year and Date: 2008-08-17
• [Presentation] Environmental alterations of three tryptophan residues in human adult hemoglobin upon ligand binding (2008)
  • Author(s): Ohkubo, K., Aki, Y., Imai, K., Nagai, Y., Nagai, M.
  • Organizer: XXI International Conference on Raman Spectroscopy ICORS 2008
  • Place of Presentation: Uxbridge (West London)
  • Year and Date: 2008-08-17
• [Presentation] 逆配向ヘムをもつヘモグロビンの酸素平衡機能と円二色性(CD) (2008)
  • Author(s): 長井雅子、長井幸史、今井清博、安藝弥生、長友重紀、山本泰彦
  • Organizer: 第35回生体分子科学討論会
  • Place of Presentation: 兵庫県立大学(兵庫県)
  • Year and Date: 2008-06-26
• [Presentation] 逆配向ヘムをもつヘモグロビンの酸素平衡機能と円二色性(CD) (2008)
  • Author(s): 長井雅子, 長井幸史, 今井清博, 安藝弥生, 長友重紀, 山本泰彦
  • Organizer: 第35回生体分子科学討論会
  • Place of Presentation: 兵庫県立大学(姫路市)
  • Year and Date: 2008-06-26
• [Presentation] Circular dichoroism and oxygen binding properties of human adult hemoglobin with reversed heme (2008)
  • Author(s): Nagai M., Nagai Y., Aki Y., Imai K., Nagatomo S., Yamamoto, Y.
  • Organizer: Joint Meeting of the Biophysical Society 52nd Annual Meeting & 16th International Biophysics Congress
  • Place of Presentation: Long Beach (USA)
  • Year and Date: 2008-02-05
• [Presentation] Circular dichoroism and oxygen binding properties of human adult hemoglobin with reversed heme (2008)
  • Author(s): Nagai, M., Nagai, Y., Aki, Y., Imai, K., Nagatomo, S. & Yamamoto, Y.
  • Organizer: Joint Meeting of the Biophysical Society 52nd Annual Meeting & 16th Ihternational Biophysics Congress
  • Place of Presentation: Long Beach (California)
  • Year and Date: 2008-02-05
• [Presentation] 有鬚動物マシコヒゲムシのもつ巨大ヘモグロビンの酸素運搬機能 (2007)
  • Author(s): 安藝弥生、中川太郎、福森義宏、長井雅子、今井清博
  • Organizer: 第45回日本生物物理学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2007-12-23
• [Presentation] ヒトヘモグロビンにおける3つのトリプトファン残基の酸素結合にともなう変化:近紫外CDおよび紫外共鳴ラマン分光による研究 (2007)
  • Author(s): 長井雅子、長井幸史、小久保昭秀、川口裕貴、安藝弥生、今井清博、長友重紀、北川禎三
  • Organizer: 第45回日本生物物理学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2007-12-23
• [Presentation] 有鬚動物マシコヒゲムシのもつ巨大ヘモグロビンの酸素運搬機能 (2007)
  • Author(s): 安藝弥生、中川太郎、長井雅子、笹山雄一、福森義宏、今井清博
  • Organizer: 第45回日本生物物理学会年会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2007-12-23
• [Presentation] ヒトヘモグロビンにおける3つのトリプトファン残基の酸素結合にともなう変化:近紫外CDおよび紫外共鳴ラマン分光による研究 (2007)
  • Author(s): 長井雅子、長井幸史、小久保昭秀、川口裕貴、安藝弥生、今井清博、長友重紀、北川禎三
  • Organizer: 第45回日本生物物理学会年会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2007-12-23
• [Presentation] マシコヒゲムシ巨大ヘモグロビンの酸素結合特性 (2007)
  • Author(s): 安藝弥生、中川太郎、福森義宏、長井雅子、今井清博
  • Organizer: 第7回日本蛋白質科学会年会
  • Place of Presentation: 仙台国際センター(宮城県)
  • Year and Date: 2007-05-25
• [Presentation] マシコヒゲムシ巨大ヘモグロビンの酸素結合特性 (2007)
  • Author(s): 安藝弥生、中川太郎、福森義宏、長井雅子、今井清博
  • Organizer: 第7回日本蛋白質科学会年会
  • Place of Presentation: 仙台国際センター(仙台市)
  • Year and Date: 2007-05-25
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