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Phasogenesis study of XOR mutant knock-in mouse.

Research Project

Project/Area Number 20590317
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionNippon Medical School

Principal Investigator

OKAMOTO Ken (2010)  Nippon Medical School, 医学部, 准教授 (60267143)

西野 朋子 (2008-2009)  Nippon Medical School, 医学部, 講師 (80075613)

Co-Investigator(Kenkyū-buntansha) MATSUMURA Tomohiro  日本医科大学, 医学部, 助教 (20297930)
KUSANO Teruo  日本医科大学, 医学部, 助教 (30434129)
岡本 研  日本医科大学, 医学部, 准教授 (60267143)
西野 武士  日本医科大学, 大学院・医学研究科, 教授 (40094312)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords分子病態学 / スーパーオキシド / キサンチン酸化還元酵素 / キサンチン脱水素酵素 / キサンチン酸化酵素 / トランスジェニックマウス / キサンチチン酸化酵素 / キサンチチン脱水素酵素 / フラビン酵素 / モリブデン酵素 / 活性酸素 / ノックインマウス / 酸化酵素型-脱水素酵素型変換 / モリブデン酸素
Research Abstract

We designed and constructed O2- hyperproduction XOR mutant knoched-in mouse which and dehydrogenase-type locked mutant knoched-in mouse. We propagated the starins. We purified mutant XOR from the knocked-in mutant mouse liver and confirmed the hyper production of superoxide anion. We are observing the phenotypes of the mutans and surveying pathological findings of organs.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (31 results)

All 2011 2010 2009 2008 Other

All Journal Article (11 results) (of which Peer Reviewed: 4 results) Presentation (19 results) Book (1 results)

  • [Journal Article] FYX-051 : a novel and potent hybrid-type inhibitor of xanthine oxidoreductase.2011

    • Author(s)
      Matsumoto K, Okamoto K, Ashizawa N, Nishino T
    • Journal Title

      J Pharmacol Exp Ther. Jan ; 336(1)

      Pages: 95-103

    • Related Report
      2010 Final Research Report
  • [Journal Article] FYX-051 : a novel and potent hybrid-type inhibitor of xanthine oxidoreductase.2011

    • Author(s)
      Matsumoto K, Okamoto K, Ashizawa N, Nishino T.
    • Journal Title

      J Pharmacol Exp Ther.

      Volume: 336 Pages: 95-103

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystal Structures of Urate Bound Form of Xanthine Oxidoreductase : Substrate Orientation and Structure of the Key Reaction Intermediate.2010

    • Author(s)
      Okamoto K, Kawaguchi Y, Eger BT, Pai EF, Nishino T.
    • Journal Title

      J Am Chem Soc.

      Volume: 132 Pages: 17080-17083

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 新世代の尿酸生成抑制剤フェブキソスタット2010

    • Author(s)
      岡本研
    • Journal Title

      薬理と治療

      Volume: 38 Pages: 955-962

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Structure and mechanism of molybdenum hydroxylase2008

    • Author(s)
      Okamoto K, Nishino T.
    • Journal Title

      [Article in Japanese]Seikagaku. Jun ; 80(6)

      Pages: 531-9

    • NAID

      10021192278

    • Related Report
      2010 Final Research Report
  • [Journal Article] Mechanism of inhibition of xanthine oxidoreductase by allopurinol : crystal structure of reduced bovine milk xanthine oxidoreductase bound with oxipurinol.2008

    • Author(s)
      Okamoto K, Eger BT, Nishino T, Pai EF, Nishino T
    • Journal Title

      Nucleosides Nucleotides Nucleic Acids. Jun ; 27(6)

      Pages: 888-93

    • Related Report
      2010 Final Research Report
  • [Journal Article] Mammalian xanthine oxidoreductase-mechanism of transition from xanthine ehydrogenase to xanthine oxidase.2008

    • Author(s)
      Nishino T, Okamoto K, Eger BT, Pai EF, Nishino T
    • Journal Title

      FEBS J. Jul ; 275(13)

      Pages: 3278-89

    • Related Report
      2010 Final Research Report
  • [Journal Article] Crystal structures of mammalian xanthine oxidoreductase bound with various inhibitors : allopurinol, febuxostat, and FYX-0512008

    • Author(s)
      Okamoto K, Nishino T
    • Journal Title

      J Nippon Med Sch. Feb ; 75(1)

      Pages: 2-3

    • NAID

      130004057313

    • Related Report
      2010 Final Research Report
  • [Journal Article] Mechanism of inhibition of xanthine oxidoreductase by allopurinol : crystal structure of reduced bovine milk xanthine oxidoreductase bound withoxipurinol.2008

    • Author(s)
      Okamoto K.
    • Journal Title

      Nucleosides Nucleotides Nucleic Acids 27

      Pages: 888-893

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mammalian xanthine oxidoreductase-mechanism of transition from xanthine dehydrogenase to xanthine oxidase.2008

    • Author(s)
      Nishino T
    • Journal Title

      FEBS J. 275

      Pages: 3278-3289

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crystal Structures of Urate Bound Form of Xanthine Oxidoreductase : Substrate Orientation and Structure of the Key Reaction Intermediate.

    • Author(s)
      Okamoto K, Kawaguchi Y, Eger BT, Pai EF, Nishino T
    • Journal Title

      J Am Chem Soc.

      Pages: 2010-2010

    • Related Report
      2010 Final Research Report
  • [Presentation] Reaction mechanism and substrate binding mode of xanthine oxidoreductase.2011

    • Author(s)
      Ken Okamoto、Yuko Kawaguchi、Teruo Kusano、Tomohiro Matsumura1、Koji Matsumoto、Takeshi Nishino
    • Organizer
      14th International Symposium on Purine and Pyrimidine Metabolism in Man
    • Place of Presentation
      東京
    • Year and Date
      2011-02-20
    • Related Report
      2010 Annual Research Report
  • [Presentation] 14th International Symposium on Purine and Pyrimidine Metabolism in Man Reaction mechanism and substrate binding mode of xanthine oxidoreductase.2011

    • Author(s)
      Ken Okamoto、Yuko Kawaguchi、Teruo Kusano、Tomohiro Matsumura 1、Koji Matsumoto、Takeshi Nishino
    • Related Report
      2010 Final Research Report
  • [Presentation] ウシキサンチン酸化還元酵素と天然基質キサンチンとの反応中間体結晶構造Structure of xanthine oxidoreductase in action ; Reaction intermediate structure of milk xanthine oxidoreductase and natural substrate xanthine.2010

    • Author(s)
      Ken Okamoto, Tomohiro Matsumura, Kusano Teruo, Koji Matsumoto, Takeshi Nishino
    • Organizer
      2010年日本生化学会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] ラットキサンチン脱水素酵素におけるCH...O結合がFADの酸化還元電位に与える影響について2009

    • Author(s)
      川口裕子, 西野朋子, 松村智裕, 岡本研, 西野武士
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2009-10-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] 新規キサンチン酸化還元酵素剤FYX-051の酵素学的,構造生物学的解析2009

    • Author(s)
      松本浩二, 岡本研, 松村智裕, 草野輝男, 西野武士
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2009-10-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] キサンチン酸化還元酵素の基質結合様式と基質活性化機構2009

    • Author(s)
      岡本研, 松村智裕, 草野輝男, 松本浩二, 西野武士
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2009-10-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] ブチロフィリンが有す多機能B30.2/SPRYドメインとミルクキサンチン脱水素酵素との結合様式について2009

    • Author(s)
      西野朋子, 李穎, 岡本研, 草野輝男, 川口裕子, 松村智裕, 他
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2009-10-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] knock-outマウスを用いたラクトペルオキシダーゼの組織局在の網羅的解析2009

    • Author(s)
      草野輝男, 松田陽子, 西野朋子, 石渡俊行, 内藤善哉, 西野武士
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2009-10-22
    • Related Report
      2009 Annual Research Report
  • [Presentation] 近赤外極微弱光検出装置を用いたヘムペルオキシダーゼ由来の一重項酸素の定量的測定法2009

    • Author(s)
      牧内正男, 辻田和宏, 草野輝男, 西野朋子, 柿沼カツ子
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2009-10-22
    • Related Report
      2009 Annual Research Report
  • [Presentation] 哺乳類ヘムペルオキシダーゼによる一重項酸素の生成2009

    • Author(s)
      辻田和宏, 草野輝男, 牧内正男, 西野朋子, 柿沼カツ子
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2009-10-22
    • Related Report
      2009 Annual Research Report
  • [Presentation] キサンチン脱水素酵素から酸化酵素に変換する際の遷移状態に於ける二量体サブユニット構造の非対称性2009

    • Author(s)
      西野朋子, 岡本研, 川口裕子, 辻井厚子, 他
    • Organizer
      第9回蛋白質科学会年会
    • Place of Presentation
      熊本
    • Year and Date
      2009-05-22
    • Related Report
      2009 Annual Research Report
  • [Presentation] ラットキサンチン脱水素酵素における機能的CH...O水素結合の存在2009

    • Author(s)
      川口裕子, 西野朋子, 松村智裕, 岡本研, 西野武士
    • Organizer
      第9回蛋白質科学会年会
    • Place of Presentation
      熊本
    • Year and Date
      2009-05-20
    • Related Report
      2009 Annual Research Report
  • [Presentation] キサンチン酸化還元酵素の基質結合様式と基質活性化機構2009

    • Author(s)
      西野朋子, 岡本研、川口裕子
    • Organizer
      日本生化学会
    • Related Report
      2010 Final Research Report
  • [Presentation] キサンチン脱水素酵素から酸化酵素に変換する際の遷移状態における構造変2009

    • Author(s)
      西野朋子, 岡本研、川口裕子
    • Organizer
      蛋白質科学会
    • Related Report
      2010 Final Research Report
  • [Presentation] 新規キサンチン酸化還元酵素阻害剤FYX-051の酵素学的,構造学的解析2009

    • Author(s)
      松本浩二, 岡本研
    • Organizer
      日本生化学会
    • Related Report
      2010 Final Research Report
  • [Presentation] キサンチン脱水素酵素/酸化酵素の変換における二量体構造の非対称性2008

    • Author(s)
      西野朋子
    • Organizer
      第81回日本生化学大会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-09
    • Related Report
      2008 Annual Research Report
  • [Presentation] ラットキサンチン酸化還元酵素におけるD/○変換時のFAD周囲の変化2008

    • Author(s)
      川口裕子
    • Organizer
      第81回日本生化学大会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-09
    • Related Report
      2008 Annual Research Report
  • [Presentation] 結晶構造から見たキサンチン酸化還元酵素阻害剤の阻害機構の解明2008

    • Author(s)
      岡本研
    • Organizer
      日本痛風核酸代謝学会学会賞受賞講演
    • Related Report
      2010 Final Research Report
  • [Presentation] キサンチン酸化還元酵素の基質結合様式と反応機構キサンチン脱水素酵素/酸化酵素の変換における二量体構造の非2008

    • Author(s)
      岡本研
    • Organizer
      日本生化学会
    • Related Report
      2010 Final Research Report
  • [Book] イラストレイテッド ハーパー・生化学 28版 第3~5章2011

    • Author(s)
      上代淑人、清水孝雄監訳
    • Publisher
      丸善株式会社
    • Related Report
      2010 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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