Theoretical Studies on Mechanisms of Prostanoid Biosyntheses

• Project/Area Number: 19550004
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Physical chemistry
• Research Institution: Ibaraki University
• Principal Investigator: MORI Seiji Ibaraki University, 理学部, 准教授 (50332549)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: プロスタノイド / プロスタグランジンD_2合成酵素 / プロスタサイクリン合成酵素 / トロンボキサン合成酵素 / シトクロムP450 / UB3LYP密度汎関数法 / エンドペルオキシド / 反応機構 / プロスタグランジンE_2合成酵素 / 鉄-ヘム錯体 / トロンボキサンA合成酵素 / 密度汎関数法 / 一電子移動 / トロンボキサンA_2合成酵素

Research Abstract

In this study, we conducted quantum chemical calculations for model reaction mechanisms of prostanoid formation reactions, which are important in biochemistry and pharmaceutical sciences. Whereas prostaglandin D_2/E_2 biosyntheses pass through two possible nucleophilic mechanisms, thromboxane and prostacyclin syntheses go through radical intermediate formation and single electron transfer. The single electron transfer step can be rationally explained by molecular orbital theory.

Research Products

• [Journal Article] UV Resonance Raman Studies on the Activation Mechanism of Human Hematopoietic Prostaglandin D_2 Synthase by a Divalent Cation, Mg^<2+> (2010)
  • Author(s): Yoshiko Uchida, Yoshihiro Urade, Seiji Mori, Takamitsu Kohzuma
  • Journal Title: J.Inorg.Biochem. 104 Pages: 331-340
• [Journal Article] UV Resonance Raman Studies on the Activation Mechanism of Human Hematopoietic Prostaglandin D_2 Synthase by a Divalent Cation, Mg^<2+> (2010)
  • Author(s): Yoshiko Uchida
  • Journal Title: J.Inorg. Biochem. 104 Pages: 331-340
  • Peer Reviewed
• [Journal Article] Density Functional Studies on Isomerization of Prostaglandin H_2 to Prostacyclin Catalyzed by Cytochrome P450 (2009)
  • Author(s): Tetsuya K. Yanai, Seiji Mori
  • Journal Title: Chem.Eur.J. 15 Pages: 4464-4473
• [Journal Article] Density Functional Studies on Isomerization of Prostaglandin H_2 to Prostacyclin Catalyzed by Cytochrome P450 (2009)
  • Author(s): 野内哲也
  • Journal Title: Chem.Eur.J. 15 Pages: 4464-4473
  • Peer Reviewed
• [Journal Article] Density Functional Studies on Thromboxane Biosynthesis : Mechanism and Role of the Heme-Thiolate System (2008)
  • Author(s): Tetsuya K. Yanai, Seiji Mori
  • Journal Title: Chem.Asian J. 3 Pages: 1900-1911
• [Journal Article] Density Functional Studies on Thromboxane Biosynthesis : Mechanism and Role of the Heme-Thiolate System (2008)
  • Author(s): 野内哲也
  • Journal Title: Chem. Asian J 3 Pages: 1900-1911
  • Peer Reviewed
• [Presentation] プロスタグランジンH_2からプロスタグランジンD_2への異性化反応に関する理論的研究:塩基と水分子が反応性に与える影響 (2009)
  • Author(s): 内記達哉
  • Organizer: 分子科学討論会2009
  • Place of Presentation: 名古屋市
  • Year and Date: 2009-09-21
• [Presentation] Important insight into Reaction Mechanisms of Organic Syntheses and Biosyntheses from View of Computational Chemistry (2009)
  • Author(s): Seiji Mori
  • Organizer: The International Symposium on Theory of Molecular Structure, Function and Reactivity, Celebrating Prof. Morokuma's 75th birthday
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2009-07-20
• [Presentation] Important insight into Reaction Mechanisms of Organic Syntheses and Biosyntheses from View of Computational Chemistry(招待講演) (2009)
  • Author(s): Seiji Mori
  • Organizer: The International Symposium on Theory of Molecular Structure, Function and Reactivity
  • Place of Presentation: 京都市
  • Year and Date: 2009-07-20
• [Presentation] Theoretical Studies on Endoperoxide O-O Bond Cleavage Catalyzed by Iron Porphyrin Complexes (2009)
  • Author(s): Jun Ochiai
  • Organizer: The International Symposium on Theory of Molecular Structure, Function and Reactivity
  • Place of Presentation: 京都市
  • Year and Date: 2009-07-20
• [Presentation] Theoretical Studies on Endoperoxide O-O Bond Cleavage Catalyzed by Iron Porphyrin Complexes (2009)
  • Author(s): Jun Ochiai
  • Organizer: 14^<th> International conference on biological inorganic chemistry(ICBIC 14)
  • Place of Presentation: 名古屋市
  • Year and Date: 2009-06-27
• [Presentation] Unusual Reactions Catalyzed by Cytochrome P450 : Density Functional Studies on Prostaglandin H_2 Isomerizations (2009)
  • Author(s): Seiji Mori
  • Organizer: 16th International Conference on Cytochrome P450
  • Place of Presentation: 沖縄県名護市
  • Year and Date: 2009-06-22
• [Presentation] プロスタグランジンH_2からプロスタグランジンD_2への異性化反応に関する理論的研究 : 塩基と水分子が反応性に与える影響 (2009)
  • Author(s): 内記達哉, 山口直人, 高田俊和, 高妻孝光, 坂田文彦, 森聖治
  • Organizer: 分子科学討論会2009
  • Place of Presentation: 名古屋
• [Presentation] Unusual Reactions Catalyzed by Cytochrome P450 : Density Functional Studies on Prostaglandin H_2 Isomerizations (2009)
  • Author(s): Seiji Mori, Tetsuya K. Yanai
  • Organizer: 16th International Conference on Cytochrome P450
  • Place of Presentation: Nago, Okinawa, Japan
• [Presentation] Unusual Reactions Catalyzed by Cytochrome P450 : Density Functional Studies on Prostaglandin H_2 Isomerizations (2008)
  • Author(s): 野内哲也
  • Organizer: 4^<th> Astan Biological Inorganic Chemistry CO ference
  • Place of Presentation: Jeju, Korea
  • Year and Date: 2008-11-11
• [Presentation] シトクロムP450によるプロスタサイクリン生合成のモデル反応機構に関する理論的研究 (2008)
  • Author(s): 森聖治
  • Organizer: 第58回錯体化学討論会
  • Place of Presentation: 金沢大学
  • Year and Date: 2008-09-20
• [Presentation] 12族金属イオンとシステインの相互作用における水和の影響に関する理論的研究 (2008)
  • Author(s): 矢口友貴
  • Organizer: 日本化学会第88春季年会
  • Place of Presentation: 東京
  • Year and Date: 2008-03-28
• [Presentation] Unusual Reactions Catalyzed by Cytochrome P450 : Density Functional Studies on Prostaglandin H_2 Isomerizations (2008)
  • Author(s): Tetsuya K. Yanai, Seiji Mori
  • Organizer: 4^<th> Asian Biological Inorganic Chemistry Conference
  • Place of Presentation: Jeju, Korea
• [Presentation] Theoretical studies on Isomerization of Prostaglandin H_2 (2008)
  • Author(s): Seiji Mori
  • Organizer: 6^<th> China-Japan Crossover Science Symposium
  • Place of Presentation: Zhengzhou, China
• [Presentation] シトクロムP450によるプロスタサイクリン生合成のモデル反応機構に関する理論的研究 (2008)
  • Author(s): 森聖治, 野内哲也
  • Organizer: 第58回錯体化学討論会
  • Place of Presentation: 金沢
• [Presentation] シクロペンタジエンの1,5-水素転移反応における速度同位体効果に関する理論的研究 (2008)
  • Author(s): 内記達哉
  • Organizer: 第2回分子科学討論会
  • Place of Presentation: 福岡
• [Presentation] シトクロムP450モデルによる、トロンボキサン生合成反応機構の理論的研究 (2007)
  • Author(s): 野内哲也, 森聖治
  • Organizer: 第57回錯体化学討論会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-09-25
• [Presentation] Theoretical Studies on Model Reaction Mechanisms of Prostanoid Synthases (2007)
  • Author(s): Seiji Mori
  • Organizer: Third Asian-Pacific Conference of Theoretical and Computational Chemistry
  • Place of Presentation: 中国,北京
  • Year and Date: 2007-09-24
• [Presentation] プロスタグランジンD2/E2合成酵素反応機構のモデル系に関する理論的研究 (茨城大院・理工1, NECソフト2, 茨城大・理3, NEC, 2P080 (2007)
  • Author(s): 山口直人, 森聖治, 高妻孝光, 高田俊和, 坂田文彦
  • Organizer: 分子科学討論会2007
  • Place of Presentation: 仙台
  • Year and Date: 2007-09-18
• [Presentation] プロスタグランジンD2/E2合成酵素反応機構のモデル系に関する理論的研究 (2007)
  • Author(s): 山口 直人
  • Organizer: 分子科学討論会2007
  • Place of Presentation: 仙台
  • Year and Date: 2007-09-18
• [Presentation] Theoretical studies on model reaction pathways of prostaglandin D_2/E_2 synthases (2007)
  • Author(s): Seiji Mori
  • Organizer: International Conference on Heteroatom Chemistry-8
  • Place of Presentation: アメリカ,カリフォルニア, Riverside
  • Year and Date: 2007-08-14
• [Presentation] Theoretical Studies on Model Reaction Mechanisms of Prostanoid Synthases (2007)
  • Author(s): Seiji Mori, Tetsuya Yanai, Naoto Yamaguchi, Takamitsu Kohzuma, Toshikazu Takada, Fumihiko Sakata
  • Organizer: Third Asian-Pacific Conference of Theoretical and Computational Chemistry
  • Place of Presentation: Beijing, China
• [Presentation] Theoretical studies on model reaction pathways of prostaglandin D_2/E_2 synthases (2007)
  • Author(s): Seiji Mori, Naoto Yamaguchi, Takamitsu Kohzuma, Toshikazu Takada, Fumihiko Sakata
  • Organizer: International Conference on Heteroatom Chemistry-8
  • Place of Presentation: Riverside, CA, USA
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