時間分解構造解析を補完する精密顕微分光計測

• Project Area: Non-equilibrium-state molecular movies and their applications
• Project/Area Number: 19H05784
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Complex systems
• Research Institution: University of Hyogo
• Principal Investigator: 久保 稔 兵庫県立大学, 理学研究科, 教授 (90392878)
• Co-Investigator(Kenkyū-buntansha): 木村 哲就 神戸大学, 理学研究科, 准教授 (70506906) ; 古谷 祐詞 名古屋工業大学, 工学(系)研究科(研究院), 准教授 (80432285)
• Project Period (FY): 2019-06-28 – 2024-03-31
• Project Status: Granted (Fiscal Year 2023)
• Budget Amount: ¥142,870,000 (Direct Cost: ¥109,900,000、Indirect Cost: ¥32,970,000); Fiscal Year 2023: ¥22,880,000 (Direct Cost: ¥17,600,000、Indirect Cost: ¥5,280,000); Fiscal Year 2022: ¥23,400,000 (Direct Cost: ¥18,000,000、Indirect Cost: ¥5,400,000); Fiscal Year 2021: ¥24,310,000 (Direct Cost: ¥18,700,000、Indirect Cost: ¥5,610,000); Fiscal Year 2020: ¥22,880,000 (Direct Cost: ¥17,600,000、Indirect Cost: ¥5,280,000); Fiscal Year 2019: ¥49,400,000 (Direct Cost: ¥38,000,000、Indirect Cost: ¥11,400,000)
• Keywords: 分子分光学 / 時間分解計測 / 超精密計測 / 蛋白質 / 生物物理学 / 時間分解X線結晶構造解析 / 時間分解紫外可視吸収分光 / 時間分解赤外分光 / 時間分解ラマン分光 / 時間分解蛍光分光 / 動的構造生物学

Outline of Research at the Start

私たちの体の中では多くの分子が働いており、エネルギー変換、物質輸送、物質代謝などの生命活動を担っています。それらの生体分子は、形を巧みに変えながら働く、謂わば、小さな分子機械です。最近、生体分子が働く様子を動画として観測できる「時間分解Ｘ線構造解析」という手法が開発されました。私たちは、紫外光、可視光、赤外光などさまざまな光を道具に、時間分解Ｘ線構造解析では原理的に観測が難しい、電子レベルの細かな解析を精密に行ないます。時間分解Ｘ線構造解析と相補的に研究を進めながら、生体分子が働くしくみを物理化学的に解明します。

Outline of Annual Research Achievements

本新学術領域の目標の一つは、時間分解結晶構造解析（分子動画）を軸としたタンパク質のダイナミクス研究を他分野と複合的に融合させて、タンパク質を設計・制御・操作する新しい学問領域を形成することである。そこで本研究では、分子動画と時間分解分光法（紫外可視吸収分光、ラマン・赤外分光、蛍光分光）との相関的・補完的解析を推進し、分子動画と他手法との融合の先鞭をつける。
本研究では溶液測定に加えて、タンパク質微結晶を測定できる顕微測定技術を開発し、分子動画との相補解析を強く推進することを課題としてきたが、本年度に至り上記すべての分光法について顕微技術開発を完了した。従って今後は、新規ロドプシン、ヘム酵素、DNAフォトリアーゼ、発光タンパク質等、分子動画研究の対象試料の分光計測に注力する。いずれも光や金属を巧みに利用するタンパク質であり、動的機能原理に興味が持たれる。
本年度の分光研究の大きな成果としては、(1)塩化物イオンポンプロドプシンNM-R3、及び(2)N2O発生酵素P450norの中間体の顕微分光解析であり、それぞれの系において分子動画との相関解析を行ない、動的メカニズムを解明した。特に(2)の研究では、中間体がラジカル種であることを赤外分光で明らかにし、メカニズムの物理化学が解明された。その他、ヘリオロドプシンやイクオリンについても、開発した顕微技術を用いた分光解析に成功しており、分子動画との相関研究を進めている。ヘリオロドプシンについては、赤外分光法により初期中間体におけるレチナール周辺の微細な水素結合変化が明らかにされた。DNAフォトリアーゼについては、2種の酵素の時間分解分光研究を進め、生物種により反応ダイナミクスが大きく異なることが見えてきた。それらフォトリアーゼの中間体構造の解明が次のステップである。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

各種顕微分光技術の開発を一通り終え、さらにそれらを用いた時間分解分光研究を構造解析と共に論文発表することができた為。

Strategy for Future Research Activity

開発した分光技術を活用して時間分解分光研究をさらに推し進める。特にヘリオロドプシン、イクオリン、DNAフォトリアーゼの中間体解析に力を入れていく。また、新学術領域公募班のもつ新たな試料も研究対象としながら、新学術領域が生み出す分子動画の精密解析を大きく展開する。

Research Products

• [Journal Article] Conformational alterations in unidirectional ion transport of a light-driven chloride pump revealed using X-ray free electron lasers (2022)
  • Author(s): Hosaka Toshiaki,Ehara Haruhiko,Kashiwagi Kazuhiro,Katsura Kazushige,Akasaka Ryogo,Hisano Tamao,Tanaka Tomoyuki,Tanaka Rie,Arima Toshi,Yamashita Ayumi,Sugahara Michihiro,Naitow Hisashi,Matsuura Yoshinori,Yoshizawa Susumu,Tono Kensuke,Owada Shigeki,Nureki Osamu,Kimura-Someya Tomomi,Iwata So,Nango Eriko,Shirouzu Mikako
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 119 Issue: 9
  • DOI: 10.1073/pnas.2117433119
  • Peer Reviewed / Open Access
• [Journal Article] A synthetic model for the possible FeIV2(μ-O)2 core of methane monooxygenase intermediate Q derived from a structurally characterized FeIIIFeIV(μ-O)2 complex. (2022)
  • Author(s): Mikata, Y., Aono, Y., Yamamoto, C., Nakayama, H., Matsumoto, A., Kotegawa, F., Harada, M., Katano, H., Kobayashi, Y., Yanagisawa, S., Kubo, M., Kajiwara, A., Kodera, M
  • Journal Title: Inorganic Chemistry Volume: 61 Issue: 2 Pages: 786-790
  • DOI: 10.1021/acs.inorgchem.1c02699
  • Peer Reviewed
• [Journal Article] Revisiting Alkane Hydroxylation with m‐CPBA (mChloroperbenzoic Acid) Catalyzed by Nickel(II) Complexes (2021)
  • Author(s): Shinke, T., Itoh, M., Wada, T., Morimoto, Y., Yanagisawa, S., Sugimoto, H., Kubo, M., Itoh S.
  • Journal Title: Chemistry A European Journal Volume: 27 Issue: 59 Pages: 14730-14737
  • DOI: 10.1002/chem.202102532
  • Peer Reviewed
• [Journal Article] Short-lived intermediate in N2O generation by P450 NO reductase captured by time-resolved IR spectroscopy and XFEL crystallography (2021)
  • Author(s): Nomura, T., Kimura, T., Kanematsu, Y., Yamada, D., Yamashita, K., Hirata, K., Ueno, G., Murakami, H., Hisano, T., Yamagiwa, R., Takeda, H., Gopalasingam, C., Kousaka, R., Yanagisawa, S., Shoji, O., Kumasaka, T., Yamamoto, M., Takano, Y., Sugimoto, H., Tosha, T., Kubo, M., Shiro, Y
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 118 Issue: 21
  • DOI: 10.1073/pnas.2101481118
  • Peer Reviewed / Open Access
• [Journal Article] Capturing structural changes of the S1 to S2 transition of photosystem II using time-resolved serial femtosecond crystallography (2021)
  • Author(s): H Li, Y Nakajima, T Nomura, M Sugahara, S Yonekura, SK Chan, T Nakane, T Yamane, Y Umena, M Suzuki, T Masuda, T Motomura, H Naitow, Y Matsuura, T Kimura, K Tono, S Owada, Y Joti, R Tanaka, E Nango, F Akita, M Kubo, S Iwata, JR Shen and M Suga
  • Journal Title: IUCrJ Volume: 8 Issue: 3 Pages: 431-443
  • DOI: 10.1107/s2052252521002177
  • NAID: 120007037379
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Inverse Hydrogen-Bonding Change Between the Protonated Retinal Schiff Base and Water Molecules upon Photoisomerization in Heliorhodopsin 48C12 (2021)
  • Author(s): Tomida Sahoko、Kitagawa Shinya、Kandori Hideki、Furutani Yuji
  • Journal Title: The Journal of Physical Chemistry B Volume: 125 Issue: 30 Pages: 8331-8341
  • DOI: 10.1021/acs.jpcb.1c01907
  • Peer Reviewed / Open Access
• [Journal Article] Time-resolved serial femtosecond crystallography reveals early structural changes in channelrhodopsin (2021)
  • Author(s): Oda Kazumasa、Nomura Takashi、Nakane Takanori、Yamashita Keitaro、Inoue Keiichi、Ito Shota、Vierock Johannes、Hirata Kunio、Maturana Andres D、Katayama Kota、( 32 authers )、Kandori Hideki、Hegemann Peter、Iwata So、Kubo Minoru、Nishizawa Tomohiro、Nureki Osamu
  • Journal Title: eLife Volume: 10 Pages: 1-21
  • DOI: 10.7554/elife.62389
  • NAID: 120006996980
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Functional Assembly of Caenorhabditis elegans Cytochrome b-2 (Cecytb-2) into Phospholipid Bilayer Nanodisc with Enhanced Iron Reductase Activity. (2021)
  • Author(s): Hamed A Abosharaf,Yuki Sakamoto,Aliaa M Radwan,Keisuke Yuzu,Mika Fujimura,Thoria Diab,Tarek M Mohamed,Eri Chatani,Tetsunari Kimura,Motonari Tsubaki
  • Journal Title: Biomolecules Volume: 11 Issue: 1 Pages: 96-96
  • DOI: 10.3390/biom11010096
  • NAID: 120007162571
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Timing of NO Binding and Protonation in the Catalytic Reaction of Bacterial Nitric Oxide Reductase as Established by Time-Resolved Spectroscopy (2020)
  • Author(s): Hanae Takeda, Tatsunari Kimura, Takashi Nomura, Masaki Horitani, Azusa Yokota, Akiko Matsubayashi, Shoko Ishii, Yoshitsugu Shiro, Minoru Kubo and Takehiko Tosha
  • Journal Title: Bulletin of the Chemical Society of Japan Volume: 93 Issue: 7 Pages: 825-833
  • DOI: 10.1246/bcsj.20200038
  • NAID: 130007879554
  • ISSN: 0009-2673, 1348-0634
  • Year and Date: 2020-07-15
  • Peer Reviewed / Open Access
• [Journal Article] Copper‐oxygen Dynamics in Tyrosinase Mechanism (2020)
  • Author(s): Fujieda Nobutaka、Umakoshi Kyohei、Ochi Yuta、Nishikawa Yosuke、Yanagisawa Sachiko、Kubo Minoru、Kurisu Genji、Itoh Shinobu
  • Journal Title: Angewandte Chemie International Edition Volume: - Issue: 32 Pages: 13385-13390
  • DOI: 10.1002/anie.202004733
  • Peer Reviewed
• [Journal Article] Enhanced redox reactivity of a nonheme iron(V)-oxo complex binding protons. (2020)
  • Author(s): Xue, S.-S., Li, X.-X., Lee, Y.-M., Seo, M. S., Kim, Y., Yanagisawa, S., Kubo, M., Jeon, Y.-K., Kim, W.-S., Sarangi, R., Kim, S. H., Fukuzumi, S., Nam, W.
  • Journal Title: J. Am. Chem. Soc. Volume: 142 Issue: 36 Pages: 15305-15319
  • DOI: 10.1021/jacs.0c05108
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Zinc Binding to Heliorhodopsin (2020)
  • Author(s): Hashimoto Masanori、Katayama Kota、Furutani Yuji、Kandori Hideki
  • Journal Title: The Journal of Physical Chemistry Letters Volume: 11 Issue: 20 Pages: 8604-8609
  • DOI: 10.1021/acs.jpclett.0c02383
  • Peer Reviewed
• [Journal Article] Direct measurements of ferric reductase activity of human 101F6 and its enhancement upon reconstitution into phospholipid bilayer nanodisc (2020)
  • Author(s): El-Behery, M., Fujimura, M., Kimura, T., Tsubaki, M.
  • Journal Title: Biochem. Biophys. Rep. Volume: 21 Pages: 100730-100730
  • DOI: 10.1016/j.bbrep.2020.100730
  • NAID: 120007026374
  • Peer Reviewed / Open Access
• [Journal Article] SACLA時分割結晶構造解析による動的構造生物学研究～酵素反応の可視化に向けた分子動画～. (2020)
  • Author(s): 久保稔
  • Journal Title: 放射光 Volume: 33 Pages: 266-270
  • Peer Reviewed
• [Journal Article] Comparing serial X-ray crystallography and microcrystal electron diffraction (MicroED) as methods for routine structure determination from small macromolecular crystals (2020)
  • Author(s): Wolff, A. M., Kubo, M. et al.
  • Journal Title: IUCrJ Volume: 7 Issue: 2 Pages: 306-323
  • DOI: 10.1107/s205225252000072x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Syntheses, characterizations, and crystal Structures of dinitrogen-divanadium complexes bearing triamidoamine ligands. (2020)
  • Author(s): Kokubo, Y., Wasada-Tsutsui, Y., Yomura, S., Yanagisawa, S., Kubo, M., Kugimiya, S., Kajita, Y., Ozawa, T., Masuda, H.
  • Journal Title: Eur. J. Inorg. Chem. Volume: 2020 Issue: 15-16 Pages: 1456-1464
  • DOI: 10.1002/ejic.201901123
  • Peer Reviewed / Open Access
• [Journal Article] Infrared spectroscopic analysis on structural changes around the protonated Schiff base upon retinal isomerization in light-driven sodium pump KR2. (2020)
  • Author(s): S. Tomida, S. Ito, T. Mato, Y. Furutani, K. Inoue, H. Kandori
  • Journal Title: Biochim Biophys Acta Bioenerg. Volume: - Issue: 7 Pages: 148190-148190
  • DOI: 10.1016/j.bbabio.2020.148190
  • Peer Reviewed
• [Journal Article] Oxidative DNA cleavage, formation of μ-1,1-hydroperoxo species, and cytotoxicity of dicopper(II) complex supported by a p-cresol-derived amide-tether ligand (2019)
  • Author(s): Kadoya, Y., Fukui, K., Hata, M., Miyano, R., Hitomi, Y., Yanagisawa, S., Kubo, M., Kodera, M.
  • Journal Title: Inorg. Chem. Volume: 58 Issue: 21 Pages: 14294-14298
  • DOI: 10.1021/acs.inorgchem.9b02093
  • Peer Reviewed
• [Journal Article] Fundamental electron-transfer and proton-coupled electron-transfer properties of Ru(iv)-oxo complexes (2019)
  • Author(s): Hiroaki Kotani, Hinatsu Shimomura, Momoka Horimoto, Tomoya Ishizuka, Yoshihito Shiota, Kazunari Yoshizawa, Sachiko Yanagisawa, Yuka Kawahara-Nakagawa, Minoru Kubo, Takahiko Kojima
  • Journal Title: Dalton Transactions Volume: 48 Issue: 35 Pages: 13154-13161
  • DOI: 10.1039/c9dt02734c
  • NAID: 120007133077
  • Peer Reviewed
• [Journal Article] Pump-Probe Time-Resolved Serial Femtosecond Crystallography at SACLA: Current Status and Data Collection Strategies (2019)
  • Author(s): Nango Eriko、Kubo Minoru、Tono Kensuke、Iwata So
  • Journal Title: Applied Sciences Volume: 9 Issue: 24 Pages: 5505-5505
  • DOI: 10.3390/app9245505
  • Peer Reviewed / Open Access
• [Presentation] マイクロ流路デバイスを用いた時間分解顕微分光法による膜輸送の分子機構解析 (2022)
  • Author(s): 木村哲就
  • Organizer: 神戸大学先端融合研究環開拓プロジェクトシンポジウム
  • Invited
• [Presentation] 膜輸送タンパク質 ABC トランスポーターの機能・構造変化の分光学的解析 (2022)
  • Author(s): 木村哲就
  • Organizer: 日本分光学会 関西支部令和３年度講演会
  • Invited
• [Presentation] Time-resolved infrared and XFEL analyses of P450nor reaction intermediates using caged-substrate. (2021)
  • Author(s): Kubo, M.
  • Organizer: Pacifichem2021
  • Int'l Joint Research / Invited
• [Presentation] Combining time-resolved XFEL crystallography with IR spectroscopy for capturing P450nor reaction intermediates. (2021)
  • Author(s): Kubo, M.
  • Organizer: Pacifichem2021
  • Int'l Joint Research / Invited
• [Presentation] 時間分解赤外分光法を用いた(6-4)光修復酵素の光修復中間体の追跡 (2021)
  • Author(s): 楞野亜衣, 山田大智, 山元淳平, 久保稔
  • Organizer: 第47回生体分子科学討論会（優秀ポスター賞受賞）
• [Presentation] Structure of a heme-oxy intermediate of cytochrome P450BM3 catalyzing a non-natural substrate (2021)
  • Author(s): 桑野わ子, 長尾聡, 當舎武彦, Joshua Kyle Stanfield, 笠井千枝, 有安真也, 荘司長三, 杉本宏, 久保稔
  • Organizer: 第59回日本生物物理学会年会（学生発表賞受賞）
• [Presentation] Infrared Spectroscopy for analyzing chemical reactions and protein functions (2021)
  • Author(s): Furutani, Y.
  • Organizer: Webinar on microscopy & microanalysis: towards high impact research series 5
  • Int'l Joint Research / Invited
• [Presentation] 時間分解赤外分光法から見たタンパク質の動的構造変化 (2021)
  • Author(s): 古谷祐詞
  • Organizer: 第94回日本生化学会大会
  • Invited
• [Presentation] Surface-enhanced infrared spectroscopy on heliorhodopsin (2021)
  • Author(s): Furutani, Y.
  • Organizer: Pacifichem2021
  • Int'l Joint Research
• [Presentation] Time-resolved spectroscopic analysis on structural changes during the transportation process of sodium pump rhodopsin KR2 (2021)
  • Author(s): Tomida, S., Wada, A., Kandori, H., Furutani, Y.
  • Organizer: Pacifichem2021
  • Int'l Joint Research
• [Presentation] 時間分解分光法を用いたヘムABCトランスポーターBhuUV-Tにおける輸送過程の速度論的解析 (2021)
  • Author(s): 木村哲就
  • Organizer: 第59回日本生物物理学会年会
  • Invited
• [Presentation] ナノディスク再構成型BhuUV-Tによる段階的な基質輸送の分光学的観察 (2021)
  • Author(s): 木村哲就, 浅田拓也, 林沙英, 鍔木基成, 城宜嗣, 杉本宏
  • Organizer: 第21回日本蛋白質科学会年会
  • Invited
• [Presentation] Developments and applications of time-resolved microspectroscopy for protein micro-crystals (2021)
  • Author(s): Kimura, T.
  • Organizer: Pacifichem2021
  • Int'l Joint Research
• [Presentation] Transmembrane electron-transfer reaction of 101F6 protein reconstituted into nanodisc (2021)
  • Author(s): Yamaguchi, A., Abosharaf, H., Tsubaki, M., Kimura, T.
  • Organizer: Pacifichem2021
  • Int'l Joint Research
• [Presentation] Structural changes of a-synuclein, an intrinsically disordered protein, along the lipid-binding and oligomerization revealed by fluorescence lifetime measurements (2021)
  • Author(s): Sasada, K., Kimura, T., Matsubara, R., Fujii, K.
  • Organizer: Pacifichem2021
  • Int'l Joint Research
• [Presentation] 光駆動イオン輸送タンパク質による光・電気エネルギー変換システムの構築 (2020)
  • Author(s): 古谷祐詞
  • Organizer: シンポジウム「社会実装を見据えた微生物・生体関連技術の最前線」, オンデマンドWeb開催（名古屋工業大学）
  • Invited
• [Presentation] Structural and functional dynamics of ABC transporters clarified by novel time-resolved measurement systems (2020)
  • Author(s): Kimura, T.
  • Organizer: International Conference on Chemical and Environmental Sciences 2020
  • Int'l Joint Research / Invited
• [Presentation] 高速分子動画撮影を補完する時間分解分光測定法の開発と微結晶タンパク質試料への応用 (2020)
  • Author(s): 木村 哲就
  • Organizer: 第93回生化学会大会
  • Invited
• [Presentation] 分子拡散混合を利用したヘムABCトランスポーターの時間分解分光解析 (2020)
  • Author(s): 木村 哲就
  • Organizer: 第2回ピコバイオロジー研究会
  • Invited
• [Presentation] XFEL結晶構造解析と振動分光法を用いたタンパク質の動的精密構造解析 (2019)
  • Author(s): 久保稔
  • Organizer: 鳥取大学GSCセミナー，鳥取大学工学部附属GSC研究センター（鳥取県・鳥取市），2019年9月27日．
  • Invited
• [Presentation] タンパク質の動的構造と機能 (2019)
  • Author(s): 久保稔
  • Organizer: 第46回生体分子科学討論会，筑波大学大学会館（茨城県つくば市），2019年6月22日．
  • Invited
• [Presentation] Membrane Protein Dynamics Studied by Time-resolved Measurements (2019)
  • Author(s): Kimura, T.
  • Organizer: Indo-Japan Joint Workshop “Frontiers in Molecular Spectroscopy: From Fundamentals to Applications in Chemistry and Biology” Nov. 1, 2019, Kobe (Japan).
  • Int'l Joint Research / Invited
• [Presentation] 赤外分光法によるイオンチャネルタンパク質におけるイオン-タンパク質間相互作用の研究 (2019)
  • Author(s): 古谷祐詞
  • Organizer: ISSPワークショップ「レチナールタンパク質の光機能発現の物理と化学」プログラム, 東京大学物性研究所（千葉県・柏市）, 2019年9月5日．
• [Presentation] Time-resolved FTIR spectroscopy for studying molecular mechanisms of sodium and lithium ion transportation of Krokinobacter rhodopsin 2 (2019)
  • Author(s): Tomida, S., Kandori, H., Furutani, Y.
  • Organizer: The 57th Annual Meeting of the Biophysical Society of Japan, Sep. 24-26, 2019, Seagaia Convention Center (Miyazaki, Miyazaki).
• [Presentation] Characterization of Antarctic inward proton pumping microbial rhodopsins (AntRs) (2019)
  • Author(s): Harris, A., Tomida, S., Schubert, L., Lazaratos, M., Watt, E., Hoang, A., Bondar, A.-N., Heberle, J., Furutani, Y., Kandori, H., Brown, L.
  • Organizer: The 57th Annual Meeting of the Biophysical Society of Japan, Sep. 24-26, 2019, Seagaia Convention Center (Miyazaki, Miyazaki).
• [Presentation] Structural features of enzyme rhodopsins revealed by infrared spectroscopy (2019)
  • Author(s): Watari, M., Ikuta, T., Hutamata, H., Yamada, D., Shihoya, W., Yoshida, K., Furutani, Y., Tsunoda, S., Nureki, O., Kandori, H.
  • Organizer: The 57th Annual Meeting of the Biophysical Society of Japan, Sep. 24-26, 2019, Seagaia Convention Center (Miyazaki, Miyazaki).
• [Book] 膜タンパク質工学ハンドブック（分担執筆：第1編 第1章 X線自由電子レーザーによる膜タンパク質の構造解析） (2020)
  • Author(s): 溝端栄一, 久保稔
  • Total Pages: 538
  • Publisher: (株)エヌ・ティー・エス
  • ISBN: 9784860435370
• [Book] Optogenetics. Light-Sensing Proteins and Their Applications in Neuroscience and Beyond Advances in Experimental Medicine and Biology (分担執筆：Part I 5. Optogenetic Modulation of Ion Channels by Photoreceptive Proteins) (2020)
  • Author(s): Hisao Tsukamoto and Yuji Furutani
  • Total Pages: 663
  • Publisher: Springer Nature Singapore Pte Ltd.
  • ISBN: 9789811587627
• [Remarks] 名古屋工業大学 古谷研究室ホームページ
  • URL: http://biophys-molsci.web.nitech.ac.jp/index.html