Computational Studies on Functions and Reactions of Prostaglandin Synthases

• Project/Area Number: 15K05411
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Organic chemistry
• Research Institution: Ibaraki University
• Principal Investigator: MORI Seiji 茨城大学, 理学部, 教授 (50332549)
• Co-Investigator(Kenkyū-buntansha): 海野 昌喜 茨城大学, 理工学研究科, 教授 (10359549)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 量子化学計算 / QM/MM法 / プロスタグランジン / 酵素 / 反応機構 / プロスタグランジン合成酵素 / プロスタグランジン類 / 酵素反応機構 / QM/MM計算 / 異性化反応 / シクロオキシゲナーゼ / 分子動力学計算

Outline of Final Research Achievements

The present studies are aimed for the functions and reaction mechanisms of prostaglandin synthases.
(1) Prostaglandin H2 synthase (cyclooxygenase): We investigated COX-2 catalyzed reaction of arachidonic acid, and we found that the activation energies for the proton abstraction step depend on the conformations of the substrate.
(2) Lipocalin-type prostaglandin D synthase: This synthase catalyzed isomerization of prostaglandin H2, and we found a pathway which involves nucleophilic attack of the thiolate ion of cysteine residue into an oxygen of endoperoxide. We also examined electronic and bonding states of bilin reductase-substrate complex.

Research Products

• [Int'l Joint Research] チェンマイ大学/カセサート大学(タイ)
• [Int'l Joint Research] Kasetsart University(タイ)
• [Int'l Joint Research] Kasetsart University(Thailand)
• [Journal Article] QM/MM Investigation for Protonation States in a Bilin Reductase PcyA-Biliverdin IXalpha Complex (2018)
  • Author(s): Eri Iijima, Matthew Paul Gleeson, Masaki Unno, Seiji Mori
  • Journal Title: ChemPhysChem Volume: 印刷中 Issue: 15 Pages: 1809-1813
  • DOI: 10.1002/cphc.201800031
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Investigation of substitution effect on fluorescence properties of Zn 2+-selective ratiometric fluorescent compounds: 2-(2′-Hydroxyphenyl) benzimidazole derivatives (2016)
  • Author(s): Kazuhiro Akutsu, Seiji Mori, Kenichi Shinmei, Hiroki Iwase, Yoshiharu Nakano, Yuki Fujii
  • Journal Title: Talanta Volume: 146 Pages: 575-584
  • DOI: 10.1016/j.talanta.2015.09.001
  • Peer Reviewed
• [Journal Article] Neutron crystallography of the complex between photosynthetic pigment of phycocyanobilin synthesizing enzyme and substrate biliverdin IXα (2015)
  • Author(s): 福山 恵一，和田 啓，杉島 正一，海野 昌喜
  • Journal Title: 生化学 Volume: 87 Issue: 6 Pages: 753-757
  • DOI: 10.14952/SEIKAGAKU.2015.870753
  • NAID: 40020687454
  • ISSN: 0037-1017
  • Year and Date: 2015-12-25
  • Peer Reviewed
• [Journal Article] Two Protonation States and Structural Features of a Bilin Reductase PcyA Revealed by Neutron Crystallography (2015)
  • Author(s): 海野昌喜、杉島正一、和田啓、萩原義徳、日下勝弘、玉田太郎、福山恵一
  • Journal Title: Nihon Kessho Gakkaishi Volume: 57 Issue: 5 Pages: 297-303
  • DOI: 10.5940/jcrsj.57.297
  • NAID: 130005105678
  • ISSN: 0369-4585, 1884-5576
  • Peer Reviewed
• [Journal Article] Insights into the Proton Transfer Mechanism of a Bilin Reductase PcyA Following Neutron Crystallography. (2015)
  • Author(s): Unno, M., Ishikawa-Suto, K., Kusaka, K., Tamada, T., Hagiwara, Y., Sugishima, M., Wada, K., Yamada, T., Tomoyori, K., Hosoya, T., Tanaka, I., Niimura, N, Kuroki, R., Inaka, K., Ishihara, M., Fukuyama, K.
  • Journal Title: J. Am. Chem. Soc. Volume: in press Issue: 16 Pages: 5452-5460
  • DOI: 10.1021/jacs.5b00645
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 酵素反応機構解析における量子化学の役割-シトクロムP450およびプロスタグランジン合成酵素を例に- (2018)
  • Author(s): 森 聖治
  • Organizer: 生物学・光源・物性研究者による量子生物学勉強会
  • Invited
• [Presentation] Theoretical Investigations of PGH2 to PGD2 Isomerization Reaction by Lipocalin-Type Prostaglandin D Synthase using Quantum Mechanics/Molecular Mechanics Method (2017)
  • Author(s): SATO, Takehiro; SHIMAMOTO, Shigeru; ARITAKE, Kosuke; URADE, Yoshihiro; MORI, Seiji
  • Organizer: 日本化学会第97春季年会
  • Place of Presentation: 横浜
  • Year and Date: 2017-03-16
• [Presentation] Computational Studies of Biosyntheses of Prostaglandins and Related Signaling Compounds (2017)
  • Author(s): Seiji Mori
  • Organizer: 6th Georgian Bay International Conference on Bioinorganic Chemistry
  • Int'l Joint Research / Invited
• [Presentation] Structural QM/MM Investigation of Bilin Reductase PcyA-substrate complex (2017)
  • Author(s): Eri Iijima, M. Paul Gleeson, Masaki Unno, Seiji Mori
  • Organizer: 2nd International Symposium of Quantum Beam Science at Ibaraki University
  • Int'l Joint Research
• [Presentation] QM/MM法によるビリン還元酵素基質複合体の構造に関する研究 (2017)
  • Author(s): 飯島 愛璃，Gleeson Paul，海野 昌喜，森 聖治
  • Organizer: 第11回分子科学討論会2017仙台
• [Presentation] Theoretical Studies of Molecular Activation Reactions-Mechanistic Insights and Rational Design of Catalysis- (2016)
  • Author(s): Seiji Mori
  • Organizer: APCTCC 7
  • Place of Presentation: 高雄、台湾
  • Year and Date: 2016-01-25
  • Int'l Joint Research / Invited
• [Presentation] Theoretical Insights into Molecular Activation Reactions (2016)
  • Author(s): Seiji Mori
  • Organizer: Thai-Japan Symposium in Chemistry
  • Place of Presentation: Chiang Mai, Thailand
  • Int'l Joint Research / Invited
• [Presentation] 光合成色素合成酵素の中性子結晶構造解析 (2015)
  • Author(s): 海野昌喜
  • Organizer: 平成27年度第1回生物構造学研究会
  • Place of Presentation: 東京
  • Year and Date: 2015-11-17
  • Invited
• [Presentation] 中性子で明らかにするビリン還元酵素の「水素原子レベル」の立体構造と反応機構 (2015)
  • Author(s): 海野昌喜
  • Organizer: 第16回大つくば物理化学セミナー
  • Place of Presentation: 群馬県草津町
  • Year and Date: 2015-11-06
• [Presentation] Computational Studies on Mechanistic Insights Into Prostaglandin Synthases (2015)
  • Author(s): Seiji Mori
  • Organizer: ICoBio 2015
  • Place of Presentation: Bogor, Indonesia
  • Year and Date: 2015-08-05
  • Int'l Joint Research / Invited
• [Remarks] 理学部物理有機化学研究室
  • URL: http://smori.sci.ibaraki.ac.jp
• [Remarks] 森研究室ホームページ
  • URL: http://smori.sci.ibaraki.ac.jp
• [Funded Workshop] 2016 Japan-Thai-Vietnam Joint Workshop for Theoretical and Computational Chemistry (2016)
  • Place of Presentation: Mito, Japan
  • Year and Date: 2016-01-18