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Neutron structure analysis of human PGD synthase for elucidation of the reaction mechanism activated by metal ions

Research Project

Project/Area Number 22550152
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemistry related to living body
Research InstitutionOsaka University

Principal Investigator

INOUE Tsuyoshi  大阪大学, 大学院・工学研究科, 教授 (20263204)

Co-Investigator(Kenkyū-buntansha) MATSUMURA Hiroyoshi  大阪大学, 大学院・工学研究科, 准教授 (30324809)
MIZOHATA Eiichi  大阪大学, 大学院・工学研究科, 助教 (90571183)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords中性子線解析 / 金属イオン / 酵素活性化機構 / 中性子線構造解析 / プロスタグランジンD合成酵素 / 反応メカニズムの解明 / 結晶の大型育成 / プロスタグランジンD合成酵素 / 反応メカニズムの明
Research Abstract

Prostaglandin D_2(PGD_2) is an allergic and inflammatory mediator produced by hematopoietic PGDS (H-PGDS) in the presence of glutathione (GSH). Previously, we found that Ca^2+and Mg^2+activated the enzyme activity and uncovered the activation mechanism by the X-ray crystal structures of the Ca^2+- and Mg^2+-bound forms of human H-PGDS at high resolution. In this study, we performed the crystallization of H-PGDS to reveal the protonation state by neutron diffraction and obtained the crystals with maximum size of 0.5 mm^3with high quality.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (36 results)

All 2012 2011 2010 Other

All Journal Article (25 results) (of which Peer Reviewed: 14 results) Presentation (10 results) (of which Invited: 3 results) Remarks (1 results)

  • [Journal Article] Human hematopoietic prostaglandin D synthase inhibitor complex structures2012

    • Author(s)
      Y. Kado, Y. Okano, N. Okazaki, K. Aritake, N. Uodome, H. Matsumura, Y. Urade & T. Inoue
    • Journal Title

      J. Biochem

      Volume: 151 Pages: 447-455

    • NAID

      10031166083

    • Related Report
      2012 Final Research Report
  • [Journal Article] Three-dimensional, non-invasive, cross-sectional imaging of protein crystals using ultrahigh resolution optical coherence tomography2012

    • Author(s)
      N. Nishizawa, S. Ishida, M. Hirose, S. Sugiyama, T. Inoue, Y. Mori, K. Itoh & H. Matsumura*
    • Journal Title

      Biomed. Opt. Express

      Volume: 3 Pages: 735-740

    • Related Report
      2012 Final Research Report
  • [Journal Article] Growth of protein crystals in hydrogels prevents osmotic shock2012

    • Author(s)
      S. Sugiyama, M. Maruyama, G. Sazaki, M. Hirose, H. Adachi, K. Takano, S. Murakami, T. Inoue, Y. Mori & H. Matsumura*
    • Journal Title

      J. Am. Chem. Soc.

      Volume: 134 Pages: 5786-5789

    • Related Report
      2012 Final Research Report
  • [Journal Article] Crystal structure of the superfamily 1 helicase from Tomato mosaic virus2012

    • Author(s)
      M. Nishikiori, S. Sugiyama, H. Xiang, M. Niiyama, K. Ishibashi, T. Inoue, M. Ishikawa, H. Matsumura & E. Katoh*
    • Journal Title

      J. Virol.

      Volume: 86 Pages: 7565-7576

    • Related Report
      2012 Final Research Report
  • [Journal Article] Effects of a forced solution flow on the step advancement on {110} faces of tetragonal lysozyme crystals: direct visualization of individual steps under a forced solution flow2012

    • Author(s)
      M. Maruyama, K. Hisato, G. Sazaki, S. Maki, Y. Takahashi, H. Yoshikawa, S. Sugiyama, H. Adachi, K. Takano, H. Matsumura, T. Inoue, S. Murakami & Y. Mori
    • Journal Title

      Cryst. Growth Des.

      Volume: 12 Pages: 2856-2863

    • Related Report
      2012 Final Research Report
  • [Journal Article] The in silico screening and X-ray structure analysis of the inhibitor complex of Plasmodium falciparum orotidine 5'-monophosphate decarboxylase2012

    • Author(s)
      Y. Takashima, E. Mizohata, S. R. Krungkrai, Y. Fukunishi, T. Kinoshita, T. Sakata, H. Matsumura, J. Krungkrai, T. Horii & T. Inoue
    • Journal Title

      J. Biochem.

      Volume: 152 Pages: 133-138

    • NAID

      10031166122

    • Related Report
      2012 Final Research Report
  • [Journal Article] Crystal structure of the N-terminal domain of the yeast general corepressor Tup1p and its functional implications2012

    • Author(s)
      H. Matsumura*, N. Kusaka, T. Nakamura, N. Tanaka, K. Sagegami, K. Uegaki, T. Inoue & Y. Mukai
    • Journal Title

      J. Biol. Chem.

      Volume: 287 Pages: 26528-26538

    • Related Report
      2012 Final Research Report
  • [Journal Article] Crystal structure of rice Rubisco and implications for activation induced by positive effectors NADPH and 6-phosphogluconate2012

    • Author(s)
      H. Matsumura, E. Mizohata, H. Ishida, A. Kogami, T. Ueno, A. Makino, T. Inoue, A. Yokota, T. Mae & Y. Kai*
    • Journal Title

      J. Mol. Biol.

      Volume: 422 Pages: 75-86

    • Related Report
      2012 Final Research Report
  • [Journal Article] Spatially precise, soft microseeding of single protein crystals by femtosecond laser ablation2012

    • Author(s)
      H. Yoshikawa, Y. Hosokawa, R. Murai, G. Sazaki, T. Kitatani, H. Adachi, T. Inoue, H. Matsumura, K. Takano, S. Murakami, S. Nakabayashi, Y. Mori & H. Matsumura
    • Journal Title

      Cryst. Growth Des.

      Volume: 12 Pages: 4334-4339

    • Related Report
      2012 Final Research Report
  • [Journal Article] Human hematopoietic prostaglandin D synthase inhibitor complex structures2012

    • Author(s)
      Yuji Kado
    • Journal Title

      J. Biochem.,

      Volume: 151(4) Issue: 4 Pages: 447-455

    • DOI

      10.1093/jb/mvs024

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Three-dimensional, non-invasive, cross-sectional imaging of protein crystals using ultrahigh resolution optical coherence tomography2012

    • Author(s)
      N.Nishizawa, S.Ishida, M.Hirose, S.Sugiyama, T.Inoue, Y.Mori, K.Itoh, H.Matsumura
    • Journal Title

      Biomedical Optics Express

      Volume: 3 Issue: 4 Pages: 735-740

    • DOI

      10.1364/boe.3.000735

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Growth of protein crystals in hydrogels prevents osmotic shock2012

    • Author(s)
      Shigeru Sugiyama
    • Journal Title

      J. Am. Chem. Soc.,

      Volume: 134(13) Issue: 13 Pages: 5786-5789

    • DOI

      10.1021/ja301584y

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystal structure of the superfamily 1 helicase from Tomato mosaic virus2012

    • Author(s)
      Masaki Nishikiori
    • Journal Title

      J. Virol.,

      Volume: 12(6) Issue: 14 Pages: 2856-2863

    • DOI

      10.1128/jvi.00118-12

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The in silico screening and X-ray structure analysis of the inhibitor complex of Plasmodium falciparum orotidine 5’-monophosphate decarboxylase2012

    • Author(s)
      Yasuhide Takashima
    • Journal Title

      J. Biochem.

      Volume: 152(2) Pages: 133-138

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystal structure of the N-terminal domain of the yeast general corepressor2012

    • Author(s)
      Hiroyoshi Matsumura
    • Journal Title

      J. Biol. Chem.

      Volume: 287(32) Issue: 32 Pages: 26528-26538

    • DOI

      10.1074/jbc.m112.369652

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystal structure of rice Rubisco and implications for activation2012

    • Author(s)
      Hiroyoshi Matsumura
    • Journal Title

      J. Mol. Biol.,

      Volume: 422(1) Issue: 1 Pages: 75-86

    • DOI

      10.1016/j.jmb.2012.05.014

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Spatially precise, soft microseeding of single protein crystalsby femtosecond laser ablation2012

    • Author(s)
      Hiroshi Yoshikawa
    • Journal Title

      Cryst. Growth Des.,

      Volume: 12(9) Issue: 9 Pages: 4334-4339

    • DOI

      10.1021/cg300018t

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human hematopoietic prostaglandin D synthase inhibitor complex structures2012

    • Author(s)
      Y.Kado, K.Aritake, N.Uodome, Y.Okano, N.Okazaki, H.Matsumura, Y.Urade, T.Inoue
    • Journal Title

      J.of Biochemistry

      Volume: (in press)

    • NAID

      10031166083

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural insight into the stereoselective production of PGF_2αby Old Yellow Enzyme from Trypanosoma cruzi2011

    • Author(s)
      N. Okamoto, K. Yamaguchi, E. Mizohata, K. Tokuoka, N. Uchiyama, S. Sugiyama, H. Matsumura, K. Inaka, Y. Urade, T. Inoue
    • Journal Title

      J. of Biochemistry

      Volume: 150 Pages: 563-568

    • Related Report
      2012 Final Research Report
  • [Journal Article] Crystallization and preliminary X-ray diffraction analysis of mouse prostaglandin F_2αsynthase, AKR1B32011

    • Author(s)
      Y. Takashima, S. Hatanaka, E. Mizohata, N. Nagata, Y. Fukunishi, H. Matsumura, Y. Urade, T. Inoue
    • Journal Title

      Acta Cryst.

      Volume: F67 Pages: 1630-1632

    • Related Report
      2012 Final Research Report
  • [Journal Article] Structural insight into the stereoselective production of PGF2a by Old Yellow Enzyme from Trypanosoma cruzi2011

    • Author(s)
      N.Okamoto, K.Yamaguchi, E.Mizohata, K.Tokuoka, N.Uchiyama, S.Sugiyama, H.Matsumura, K.Inaka, Y.Urade, T.Inoue
    • Journal Title

      J.of Biochemistry

      Volume: 150(5) Issue: 5 Pages: 563-568

    • DOI

      10.1093/jb/mvr096

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystallization and preliminary X-ray diffraction analysis of mouse prostaglandin F2a synthase, AKR1B32011

    • Author(s)
      Y.Takashima, S.Hatanaka, E.Mizohata, N.Nagata, Y.Fukunishi, H.Matsumura, Y.Urade, T.Inoue
    • Journal Title

      Acta Cryst

      Volume: F67 Issue: 12 Pages: 1630-1632

    • DOI

      10.1107/s1744309111036165

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure of hyperthermophilic b-glucosidase from Pyrococcus furiosus2011

    • Author(s)
      Y.Kado, T.Inoue, K.Ishikawa
    • Journal Title

      Acta Cryst

      Volume: F67 Issue: 12 Pages: 1473-1479

    • DOI

      10.1107/s1744309111035238

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure of the inhibitor complex of old yellow enzyme from Trypanosoma cruzi2011

    • Author(s)
      Keishi Yamaguchi, Naoki Okamoto, Keiji Tokuoka, Shigeru Sugiyama, Nahoko Uchiyama, Hiroyoshi Matsumura, Koji Inaka, Yoshihiro Urade, Tsuyoshi Inoue
    • Journal Title

      Journal of Synchrotron Radiation

      Volume: 18 Pages: 66-69

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Catalytic mechanism of the primary human prostaglandin F_2α synthase, aldo-keto reductase 1B1-prostaglandin D_2 synthase activity in the absence of NADP(H)2011

    • Author(s)
      Nanae Nagata, Yukiko Kusakari, Yoshifumi Fukunishi, Tsuyoshi Inoue, Yoshihiro Urade
    • Journal Title

      The FEBS Journal

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Atomic resolution structure of copper-containing nitrite reductase provides insights into common properties of type 2 copper-containing enzymes2012

    • Author(s)
      Y. Fukuda, T. Tamada, H. Takami, T. Inoue, M. Nojiri
    • Organizer
      Asian Crystallographic Association (AsCA) 2012
    • Place of Presentation
      Adelaide (Australia)
    • Related Report
      2012 Final Research Report
  • [Presentation] ブドウ由来フラボノール3位グルクロン酸転移酵素(VvGT5)のX線結晶構造解析2012

    • Author(s)
      井上豪
    • Organizer
      日本農芸化学会関西支部 第474回講演会
    • Place of Presentation
      京都府立大学合同講義棟第三講義室
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] ブドウ由来糖転移酵素VvGT5のX線結晶構造解析2012

    • Author(s)
      井上豪
    • Organizer
      第2回CSJ化学フェスタ(2012)
    • Place of Presentation
      東京工業大学 大岡山キャンパス
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] ブドウ由来UDP糖依存性グリコシルトランスフェラーゼの基質特異性の構造基盤の解明2012

    • Author(s)
      井上豪
    • Organizer
      平成24年度日本結晶学会年会
    • Place of Presentation
      東北大学片平キャンパス
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Structural basis enzymes in the pyrimidine biosynthetic pathway of human malaria parasite Plasmodium falciparumfor in silicodrug design2011

    • Author(s)
      Y. Takashima, E. Mizohata, K. Tokuoka, Y. Kusakari, T. Uchida, S. R. Krungkrai, H. Matsumura, J. Krungkrai, T. Horii, T. Inoue
    • Organizer
      International Union of Crystallography
    • Place of Presentation
      Madrid(Spain)
    • Related Report
      2012 Final Research Report
  • [Presentation] Structural basis enzymes in the pyrimidine biosynthetic pathway of human malaria parasite Plasmodium falciparum for in silico drug design2011

    • Author(s)
      Y.Takashima, E.Mizohata, K.Tokuoka, Y.Kusakari, T.Uchida, S.R.Krungkrai, H.Matsumura, J.Krungkrai, T.Horii, T.Inoue
    • Organizer
      International Union of Crystallography
    • Place of Presentation
      Madrid (Spain)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Trypanosoma cruzi由来Old Yellow Enzymeの阻害剤複合体の結晶構造2010

    • Author(s)
      山口桂史、岡本尚毅、徳岡啓司、杉山成、溝端栄一、松村浩由、伊中浩治、内山奈穂子、裏出良博
    • Organizer
      第10回日本蛋白質科学会年会
    • Place of Presentation
      北海道・札幌市
    • Year and Date
      2010-06-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] Novel Approach for Growth of High-Quality and Large Protein Crystals2010

    • Author(s)
      H. Matsumura, K. Kakinouchi, N. Shimizu, S. Sugiyama, Y. Takahashi, M. Maruyama, R. Murai, H. Adachi, K. Takano, S. Murakami, T. Inoue, Y. Mori
    • Organizer
      3th International Conference on the Crystallization of Biological Macromolecules
    • Place of Presentation
      Dublin(Ireland)
    • Related Report
      2012 Final Research Report
  • [Presentation] Protein Crystallization in Agarose Gel with High Strength2010

    • Author(s)
      S. Sugiyama, M. Hirose, R. Murai, Y. Takahashi, M. Maruyama, G. Sazaki, H. Adachi, K. Takano, S. Murakami, T. Inoue, H. Matsumura
    • Organizer
      3th International Conference on the Crystallization of Biological Macromolecules
    • Place of Presentation
      Dublin(Ireland)
    • Related Report
      2012 Final Research Report
  • [Presentation] Development of the new protein crystallization techniques and application for structural analysis of target Enzymes

    • Author(s)
      T. Inoue, H. Adachi, K. Takano, H. Matsumura, S. Murakami, Y. Mori
    • Organizer
      The 10th KIAS Conference on Protein Structure for structural and Function
    • Place of Presentation
      Korea Institute for Advanced Study, Seoul, Korea
    • Related Report
      2012 Final Research Report
  • [Remarks] 井上豪Home Page

    • URL

      http://www.chem.eng.osaka-u.ac.jp/~inoue-tken/ja/staffs/inoue/index.html

    • Related Report
      2012 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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