Exploitation of tissue specific proton pump inhibitors

• Project/Area Number: 21890239
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Iwate Medical University
• Principal Investigator: SEKIYA Mizuki Iwate Medical University, 薬学部, 助教 (70509033)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥2,652,000 (Direct Cost: ¥2,040,000、Indirect Cost: ¥612,000); Fiscal Year 2010: ¥1,261,000 (Direct Cost: ¥970,000、Indirect Cost: ¥291,000); Fiscal Year 2009: ¥1,391,000 (Direct Cost: ¥1,070,000、Indirect Cost: ¥321,000)
• Keywords: 酵素 / プロトンATPase / V-ATPase / ATP合成酵素 / 阻害剤

Research Abstract

I analyzed rotation mechanism of F-type ATPase using single molecule observation system in order to understand those of proton ATPases including V-type ATPase in osteoclast. Thermodynamic analysis of the rotation indicated that a specific γ-β interaction in F1 sector is important for flat energy pathway during the rotation, and F1 requires ~2-fold higher activation energy for the transition from the active state (continuous rotation) to the inhibited state (~1 sec pausing) compared with that for normal steady-state rotation during the active state.

Research Products

• [Journal Article] Synthesis and innate immunosuppressive effect of 1,2-cyclopentanediol derivatives (2011)
  • Author(s): Haruhisa Kikuchi, Kaori Okazaki, Mizuki Sekiya, Yasuyuki Uryu, Yasuhiro Katou, Kazunori Ueda, Shoichiro Kurata, Yoshiteru Oshima
  • Journal Title: Eur.J.Med.Chem 46 Pages: 1263-1273
  • Peer Reviewed
• [Journal Article] Synthesis and innate immunosuppressive effect of 1,2-cyclopentanediol derivatives. (2011)
  • Author(s): Kikuchi H., Okazaki K., Sekiya M., Uryu Y., Katou Y., Ueda K., Kurata S., Oshima Y.
  • Journal Title: Eur.J.Med.Chem Volume: 46 Pages: 1263-1273
  • Peer Reviewed
• [Journal Article] プロトンポンプATPaseの回転触媒機構 (2010)
  • Author(s): 中西真弓、關谷瑞樹
  • Journal Title: 日本応用酵素協会誌 45 Pages: 11-18
• [Journal Article] Single molecule behavior of inhibited and active state of Escherichia coli ATP synthase F1 rotation (2010)
  • Author(s): Mizuki Sekiya, Hiroyuki Hosokawa, Mayumi Nakanishi-Matsui, Robert K. Nakamoto, Marwan K. Al-Shawi, Masamitsu Futai
  • Journal Title: J.Biol.Chem 285 Pages: 42058-42067
  • Peer Reviewed
• [Journal Article] The mechanism of rotating proton pumping ATPases (2010)
  • Author(s): Mayumi Nakanishi-Matsui, Mizuki Sekiya, Robert. K. Nakamoto, Masamitsu Futai
  • Journal Title: Biochim.Biophys.Acta 1797 Pages: 1343-1352
  • Peer Reviewed
• [Journal Article] Temperature dependence of single molecule rotation of the Escherichia coli ATP synthase F_1 sector reveals the importance of γ-β subunit interactions in the catalytic dwell. (2010)
  • Author(s): Sekiya M., Hosokawa H., Nakanishi-Matsui M., Al-Shawi MK., Nakamoto RK., Futai M.
  • Journal Title: J Biol.Chem. Volume: 285 Pages: 42058-42067
  • Peer Reviewed
• [Journal Article] プロトンポンプATPaseの回転触媒機構 (2010)
  • Author(s): 中西真弓、關谷瑞樹
  • Journal Title: 日本応用酵素協会誌 Volume: 45 Pages: 11-18
• [Journal Article] Temperature dependence of single molecule rotation of the Escherichia coli ATP synthase F1 sector reveals the importance of... subunit interactions in the catalytic dwell (2009)
  • Author(s): Mizuki Sekiya, Robert K. Nakamoto, Marwan K. Al-Shawi, Mayumi Nakanishi-Matsui, Masamitsu Futai
  • Journal Title: J.Biol.Chem 284 Pages: 22401-22410
  • Peer Reviewed
• [Journal Article] Revised structure and synthesis of celastramycin a, a potent innate immune suppressor (2009)
  • Author(s): Haruhisa Kikuchi, Mizuki Sekiya, Yasuhiro Katou, Kazunori Ueda, Takahiro Kabeya, Shoichiro Kurata, Yoshiteru Oshima
  • Journal Title: Org.Lett 11 Pages: 1693-1695
  • Peer Reviewed
• [Journal Article] Temperature dependence of single molecule rotation of the Escherichia coli ATP synthase F1 sector reveals the importance of γ-β subunit interactions in the catalytic dwell. (2009)
  • Author(s): Sekiya M., Nakamoto RK., Al-Shawi MK., Nakanishi-Matsui M., Futai M.
  • Journal Title: J.Biol.Chem. 284 Pages: 22401-22410
  • Peer Reviewed
• [Journal Article] The mechanism of rotating proton pumping ATPases
  • Author(s): Nakanishi-Matsui M, Sekiya M, Nakamoto RK, Futai M.
  • Journal Title: Biochim.Biophys.Acta (In press)
  • Peer Reviewed
• [Presentation] Single molecule detection of an intrinsic inhibited state of the E. coli F_1 ATPase (2010)
  • Author(s): 関谷瑞樹, 細川浩之, Robert K., Nakamoto, Marwan K., Al-Shawi, 中西(松井)真弓, 二井將光
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-09
• [Presentation] Effect of ε subunit on F_1 rotation in E.coli ATP synthase (2010)
  • Author(s): 関谷瑞樹, 西山枝里, Robert K., Nakamoto, 中西(松井)真弓, 二井將光
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-09
• [Presentation] The intrinsic inhibition of ATP hydrolysis in E.coli ATP synthase : Single molecule observation (2010)
  • Author(s): Sekiya M., Hosokawa H., Nakanishi-Matsui M., Al-Shawi MK., Nakamoto RK., Futai M.
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-09
• [Presentation] The intrinsic inhibition mechanism of ATP hydrolysis in ATP synthase : Single molecule observation. (2010)
  • Author(s): 関谷瑞樹, 細川浩之, 中西(松井)真弓, 二井將光
  • Organizer: FAOBMB Symposium (OzBio2010)
  • Place of Presentation: Melbourne
  • Year and Date: 2010-09-27
• [Presentation] The intrinsic inhibition mechanism of ATP hydrolysis in ATP synthase : Single molecule observation (2010)
  • Author(s): Sekiya M., Hosokawa H., Nakanishi-Matsui M., Futai M.
  • Organizer: OZBIO2010
  • Place of Presentation: Melbourne Convention & Exhibition Centre
  • Year and Date: 2010-09-27
• [Presentation] Al-Shawi, Mayumi Nakanishi-Matsui, and Masamitsu Futai,Thermodynamics of single molecule rotation of Escherichia coli F-ATPase. (2010)
  • Author(s): Mizuki Sekiya, Hiroyuki Hosokawa, Robert K. Nakamoto, Marwan K.
  • Organizer: FASEB Summer research conferences
  • Place of Presentation: Colorado,USA.
  • Year and Date: 2010-06-09
• [Presentation] Thermodynamics of single molecule rotation of Escherichia coli F-ATPase (2010)
  • Author(s): Sekiya M., Hosokawa H., Nakanishi-Matsui M., Al-Shawi MK., Nakamoto RK., Futai M.
  • Organizer: 2010 FASEB Summer Research Conferences Transport ATPases : From Molecules to Maladies
  • Place of Presentation: Snowmass Village, Colorado
  • Year and Date: 2010-06-07
• [Presentation] 大腸菌ATP合成酵素におけるεサブユニットの役割 (2010)
  • Author(s): 関谷瑞樹, 中西(松井)真弓, 西山枝里, Robert K., Nakamoto, Marwan K., Al-Shawi, 二井將光
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡(東日本大震災のため中止)
  • Year and Date: 2010-03-30
• [Presentation] 大腸菌 ATP 合成酵素によるATP 加水分解反応の阻害機構 (2010)
  • Author(s): 関谷瑞樹、細川浩之、中西(松井)真弓、二井將光
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 就実大学(岡山)
  • Year and Date: 2010-03-29
• [Presentation] 大腸菌ATP合成酵素によるATP加水分解反応の阻害機構 (2010)
  • Author(s): 関谷瑞樹、細川浩之、中西(松井)真弓、二井將光
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山県就実大学
  • Year and Date: 2010-03-29
• [Presentation] ATP 合成酵素の回転における熱力学と γ.β サブユニット間の相互作用の重要性 (2009)
  • Author(s): 関谷瑞樹, Robert K., Nakamoto, Marwan K., Al-Shawi, 中西(松井)真弓, 二井將光
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2009-10-23
• [Presentation] Pauses of subunit rotation of Escherichia coli ATP synthase F_1 Sector. (2009)
  • Author(s): 細川浩之, 中西(松井)真弓, 関谷瑞樹, 二井將光
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2009-10-22
• [Presentation] ATP合成酵素の回転における熱力学とγ-βサブユニット間の相互作用の重要性 (2009)
  • Author(s): 關谷瑞樹, Robert K.Nakamoto, MarwanK.AI-Shawi, 中西(松井)真弓, 二井將光
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2009-10-22
• [Presentation] Thermodynamics of single molecule rotation of proton pumping ATPase (2009)
  • Author(s): 関谷瑞樹
  • Organizer: 21st IUBMB and the 12th FAOBMB International Congress of Biochemistry and Molecular Biology
  • Place of Presentation: 上海国際会議センター
  • Year and Date: 2009-08-06
• [Presentation] Thermodynamics of single molecule rotation of proton pumping ATPase (2009)
  • Author(s): Mizuki Sekiya
  • Organizer: 21st IUBMB and the 12th FAOBMB Internationa I Congress of Biochemistry and Molecular Biology
  • Place of Presentation: 上海国際会議センター
  • Year and Date: 2009-08-06
• [Presentation] Thermodynamics of single molecule rotation of Escherichia coli ATP synthase. (2009)
  • Author(s): 関谷瑞樹
  • Organizer: JBS Biofrontier Symposium on Biochemistry of pH Homeostasis and Proton Circuit
  • Place of Presentation: 岩手医科大学矢巾キャンパス
  • Year and Date: 2009-07-24
• [Presentation] Thermodynamics of single molecule rotation of Escherichia coli ATP synthase (2009)
  • Author(s): Mizuki Sekiya
  • Organizer: JBS Biofrontier Symposium on Biochemistry of pH Homeostasis and Proton Circuit
  • Place of Presentation: 岩手医科大学矢巾キャンパス
  • Year and Date: 2009-07-24
• [Presentation] Thermodynamics of Escherichia coli ATP synthase F1 sector rotation and effects of γ subunit Met23 replacement. (2009)
  • Author(s): 関谷瑞樹
  • Organizer: Iwate International Symposium on Biochemical Approaches to Drug Discovery
  • Place of Presentation: 岩手医科大学矢巾キャンパス
  • Year and Date: 2009-05-15
• [Presentation] Thermodynamics of Escherichia coli ATP Synthase F_1 Sector Rotation and Effects of γ Subunit Met23 Replacement (2009)
  • Author(s): Mizuki Sekiya
  • Organizer: Iwate International Symposium on Biochemical Approaches to Drug Discovery
  • Place of Presentation: 岩手医科大学矢巾キャンパス
  • Year and Date: 2009-05-15
• [Presentation] ATP 合成酵素の回転における熱力学と β.γ サブユニット間の相互作用による影響 (2009)
  • Author(s): 関谷瑞樹、中西(松井)真弓、二井將光
  • Organizer: 生化学会東北支部会
  • Place of Presentation: 東北大学片平さくらホール
  • Year and Date: 2009-05-09
• [Presentation] ATP合成酵素の回転における熱力学とβ-γサブユニット間の相互作用による影響 (2009)
  • Author(s): 關谷瑞樹、中西(松井)真弓、二井將光
  • Organizer: 生化学会東北支部会
  • Place of Presentation: 東北大学片平さくらホール
  • Year and Date: 2009-05-09
• [Remarks] ホームページ等