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Determination of fine structure of the molybdo-enzyme and mechanism of hydroxylation and protein vibration.

Research Project

Project/Area Number 16205021
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemistry related to living body
Research InstitutionNippon Medical School

Principal Investigator

NISHINO Takeshi  Nippon Medical School, Graduate School of Medicine, Professor (40094312)

Co-Investigator(Kenkyū-buntansha) OKAMOTO ken  Nippon Medical School, 医学部, Assoc.Professor (60267143)
MATSUMURA Tomohiro  Nippon Medical School, 医学部, Assist.Professor (20297930)
KIKUCHI Hiroto  Nippon Medical School, 医学部, Assoc.Professor (00224907)
Project Period (FY) 2004 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥48,230,000 (Direct Cost: ¥37,100,000、Indirect Cost: ¥11,130,000)
Fiscal Year 2007: ¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000)
Fiscal Year 2006: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Fiscal Year 2005: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Fiscal Year 2004: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
KeywordsThree-dimensional-structure based drug design / Anti-gout drug / ALS / Xanthine oxidase / Molecular dynamics / x-ray crystallography / 蛋白質の基準振動計算 / モリブデン金属 / モリブデン水酸化機構 / キサンチン脱水素酵素 / X-線結晶構造 / 活性酸素 / モリブデン配位子 / キサンチン脱水素酸素
Research Abstract

We have been working on the conformational changes and vibration movement of protein structure of xanthine oxidoreductase that potentially produces active oxygen species. Outline of the significant results as follows : 1) We have assigned the atom ligands and their geometries of the molybdenum atom of the MoCo center in the catalytic center of xanthine oxidoreductase by X-ray crystallographic analysis. In contrast to the previous reports, comparison between the electron densities of the sulfo and desulfo forms indicated that the oxygen atom locates at the apical position while the sulfo atom locates at the equatorial position. These results account for the hydride transfer mechanism during hydroxylation reaction proposed in the structure of reaction intermediate of the enzyme with slow substrate of FYX-051. We also proposed the role of amino acid residues located in the active site cavities in the hydroxylation of purine substrates by site directed mutagenesis experiments. 2) We have revealed the overall mechanism of the conversion from the dehydrogenase to the oxidase revealed by the three-dimensional structures analysis, and have published the invited review papers. 3) In order to account for the different effects of inhibitors on the mammalian and bacterial enzymes observed in the anti-gout drugs, we have determined the molecular dynamics by computer simulation analysis. The results suggested that the dynamics of the hydrophobic peptide exist in the cavity differ significantly between bacterial and mammalian enzymes. 4) We have constructed transgenic mouse that produces large amount of superoxide compare to the normal enzyme. Analyses of phenotype are still under way. We have analyzed the effects of inhibitors of xanthine oxidoreductase on the ALS model mouse, it was found that some of the inhibitors are quite effective for therapeutic usage.

Report

(5 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (116 results)

All 2008 2007 2006 2005 2004

All Journal Article (54 results) (of which Peer Reviewed: 19 results) Presentation (52 results) Book (9 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Dimer-Oligomer Interconversion of Wild-type and Mutant Rat 2-Cys Peroxiredoxi-n2008

    • Author(s)
      Tormohiro Matsumura
    • Journal Title

      J.Biol.Chem. 283・1

      Pages: 284-293

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Mammalian xanthine oxidoreductase-mechanism of transition from xanthine dehydrogenase to xanthine oxidase2008

    • Author(s)
      Tomoko Nishino
    • Journal Title

      FEBS.J 275

      Pages: 3278-3289

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Dimer-Oligomer Interconversion of Wild-type and Mutant Rat2-Cys Peroxiredoxin2008

    • Author(s)
      Tomohiro Matsumura
    • Journal Title

      J.Biol.Chem. 283(1)

      Pages: 284-893

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Mammalian xanthine oxidoreductase - mechanism of transition from xanthine dehydrogenase to xanthine oxidase2008

    • Author(s)
      Tomoko Nishino
    • Journal Title

      FEBS.J. 275

      Pages: 3278-3289

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Xanthine oxidoreductase2008

    • Author(s)
      Takeshi Nishino, Emil F.Pai
    • Journal Title

      HANDBOOK OF METALLOPROTEINS(Wiley)

      Pages: 1-14

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Dimer-Oligomer Interconversion of Wild-type and Mutant Rat 2-Cys Peroxiredoxin2008

    • Author(s)
      Tomohiro Matsumura
    • Journal Title

      J. B. C. 283(1)

      Pages: 284-293

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Two Mutations Convert Mammalian xanthine Oxidoreductase to Highly Superoxide-productive Xanthine Oxidase2007

    • Author(s)
      Ryosuke Asai
    • Journal Title

      J.Biochem. 141(4)

      Pages: 525-534

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Human Xanthine Oxidase Changes Its Substrate Specificity to Aldehyde.Oxidase Typeuppo Mutation of Ammo Actd Kesidues in the Active Site.Roles of Active Site Residues in Binding and Activation of Purine Substrate.2007

    • Author(s)
      Yuichiro Yamaguchi
    • Journal Title

      J.Biochem. 141(4)

      Pages: 513-524

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Two Mutations Convert Mammalian Xanthine Oxidoreductase to Highly Superoxide-productive Xanthine Oxidase2007

    • Author(s)
      Ryosuke Asai
    • Journal Title

      J.Biochem. 141(4)

      Pages: 525-534

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Human Xanthine Oxidase Changes Its Substrate Specificity to Aldehyde Oxidase Type upon Mutation of Amino Acid Residues in the Active Site : Roles of Active Site Residues in Binding and Activation of Purine Substrate2007

    • Author(s)
      Yuichiro Yamaguchi
    • Journal Title

      J.Biochem. 141(4)

      Pages: 513-524

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Two Mutations Convert Mammalian Xanthine Oxidoreductase to Highly Superoxide-productive Xanthine Oxidase2007

    • Author(s)
      Ryosuke Asai
    • Journal Title

      J. Biochem. 141(4)

      Pages: 525-534

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human Xanthine Oxidase Changes Its Substrate Specificity to Aldehyde Oxidase Type upon Mutation Amino Acid Residues in the Active Site: Roles of Active Site Residues in and Activation of Purine substrate.2007

    • Author(s)
      Yuichiro Yamaguchi
    • Journal Title

      J. Biochem. 141(4)

      Pages: 513-524

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Proteome Analysis of Human Placenta: Pre-eclampsia Versus Normal Pregnancy2007

    • Author(s)
      Katsuya Mine
    • Journal Title

      Placenta 28

      Pages: 676-687

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human Xanthine Oxidase Changes Its Substrate Specificity to Aldehyde Oxidase Type upon Mutation of Amino Acid Residues in the Active Site : Roles of Active Site Residues in Binding and Activation of Purine Substrate.2007

    • Author(s)
      Yuichiro Yamaguchi
    • Journal Title

      Joournal of Biochemistry 10.1093/jb/mvm053

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Two Mutations Convert Mammalian Xanthine Oxidoreductase to Highly Superoxide-Productive Xanthine Oxidase2007

    • Author(s)
      Ryousuke Asai
    • Journal Title

      Journal of Biochemistry 10.1093/jb/mvm054

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A line-shape function in terms of changes in both molecular structure and force constants : A Gaussian approximation2006

    • Author(s)
      Keisho Umesaki, et al.
    • Journal Title

      J.Chem.Phys. 124・7

      Pages: 1-11

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] XORによる活性酸素生成機構:レドックスシグナル発生の分子基盤2006

    • Author(s)
      岡本研
    • Journal Title

      実験医学 24・12

      Pages: 1724-1730

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] A line-shape funcion in terms of changes in both molecular structure and force constants : A Gaussian approximation2006

    • Author(s)
      Umesaki K, Kikuchi H
    • Journal Title

      J.Chem.Phys. 124

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] A line-shape function in terms of changes in both molecular structure and force constants : A Gaussian approximation2006

    • Author(s)
      Keisho Umesaki, et al
    • Journal Title

      J.Chem.Phys. 124(7)

      Pages: 1-11

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Mechanism of formation of active oxygen species in XOR : Molecular basis of redox signaling2006

    • Author(s)
      Ken Okamoto
    • Journal Title

      Experimental Medicine. 24

      Pages: 1724-1730

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] A line-shape function in terms of changes in both molecular structure and force constants : A Gaussian approximation2006

    • Author(s)
      Umesaki K., Kikuchi H.
    • Journal Title

      J.Chem.Phys. 124

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Proteome Analysis of Human Placenta : Pre-eclampsia Versus Normal Pregnancy2006

    • Author(s)
      Katsuya Mine
    • Journal Title

      Placenta 10.1016/j.placenta.2006.10.005

    • Related Report
      2006 Annual Research Report
  • [Journal Article] XORによる活性酸素生成機構 : レドックスシグナル発生の分子基盤2006

    • Author(s)
      岡本研
    • Journal Title

      実験医学 24・12

      Pages: 1724-1730

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A line-shape function in terms of changes in both molecular structure and force constants : A Gaussian approximation2006

    • Author(s)
      Keisho Umesaki et al.
    • Journal Title

      J.Chem.Phys. 124・7

      Pages: 1-11

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Electron transfer chain reaction of the extracellulr flavocytochrome collobiose dehydrogenase for the basidiomycete Phanerochaete chrysosporium.2005

    • Author(s)
      Kiyohiko Igarashi, et al
    • Journal Title

      FEBS.J. 272・11

      Pages: 2869-2877

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Mecchanism of the Conversion of Xanthine Dehydrogenase to Xanthine Oxidase2005

    • Author(s)
      Tomoko Nishino, et al.
    • Journal Title

      J.Biol.Chem. 280・26

      Pages: 24888-24894

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Expression of Nox genes in rat organs, mouse oocytes, and sea urchin eggs2005

    • Author(s)
      Y.Maru, et al.
    • Journal Title

      DNA Seq. 16・2

      Pages: 83-88

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Redox system expression in the motor neurons in amyotrophic lateral sclerosis(ALS) : immunohistochemical studies on sporadic ALS, superoxide dismutasel(SODI)-mutated familial ALS, and SODI-mutated ALS animal models2005

    • Author(s)
      S.Kato, et al.
    • Journal Title

      Acta Neuropathol. 110・2

      Pages: 101-112

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Electron transfer chain reaction of the extracellular flavocytochrome cellobiose dehydrogenase from the basidiomycete Phanerochaete chrysosporium2005

    • Author(s)
      Kiyohiko Igarashi, et al
    • Journal Title

      FEBS.J. 272(11)

      Pages: 2869-2877

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Mechanism of the Conversion of Xanthine Dehydrogenase to Xanthine Oxidase2005

    • Author(s)
      Tomoko Nishino, et al
    • Journal Title

      J.Biol.Chem. 280(26)

      Pages: 24888-24894

    • NAID

      10021987364

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Expression of Nox genes in rat organs, mouse oocytes, and sea urchin eggs2005

    • Author(s)
      Y.Maru, et al
    • Journal Title

      DNA Seq. 16(2)

      Pages: 83-88

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Redox system expression in the motor neurons in amyotrophic lateral sclerosis(ALS) : immunohistochemical studies on sporadic ALS, superoxide dismutase 1(SOD1)-mutated familial ALS, and SOD1-mutated ALS animal models2005

    • Author(s)
      S.Kato, et al
    • Journal Title

      Acta Neuropathol. 110(2)

      Pages: 101-112

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The Mammalian Xanthine Oxidoreductase : Mechanisms of Hydroxylation Reaction and Dehydrogenase / Oxidase Conversion2005

    • Author(s)
      Ken Okamoto
    • Journal Title

      FLAVINS AND FLAVOPROTEINS 2005(ARchi Tect Inc.)

      Pages: 379-390

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Function Cellobiose Dehydrogenase and β-Glucosidase in Cellulose Degrading Culture of Basidiomycete Phanerochaete chrysosporium2005

    • Author(s)
      Kiyohiko Igarashi
    • Journal Title

      FLAVINS AND FLAVOPROTEINS 2005(ARchi Tect Inc.)

      Pages: 429-432

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Febuxostat, a Novel Non-Purine Selective Inhibitor of Xanthine Oxidase -Mechanism of Action and Clinical Application-2005

    • Author(s)
      Shiro Kondo
    • Journal Title

      FLAVINS AND FLAVOPROTEINS 2005(ARchi Tect Inc.)

      Pages: 895-898

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Mechanism of Xanthine Oxidoreductase Inhibition by Y-700 and its Hypouricemic Effect in Humans2005

    • Author(s)
      Atsushi Fukunari
    • Journal Title

      FLAVINS AND FLAVOPROTEINS 2005(ARchi Tect Inc.)

      Pages: 899-904

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Mechanism of the Conversion of Xanthine Dehydrogenase to Xanthine Oxidase2005

    • Author(s)
      Tomoko Nishino et al.
    • Journal Title

      J.Biol.Chem. 280・26

      Pages: 24888-24894

    • NAID

      10021987364

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Expression of Nox genes in rat organs, mouse oocytes, and sea urchin eggs2005

    • Author(s)
      Y.Maru et al.
    • Journal Title

      DNA Seq. 16・2

      Pages: 83-88

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Redox system expression in the motor neurons in amyotrophic lateral sclerosis (ALS) : immunohistochemical studies on sporadic ALS, superoxide dismutase 1(SOD1)-mutated familial ALS, and SOD1-mutated ALS animal models2005

    • Author(s)
      S.Kato et al.
    • Journal Title

      Acta Neuropathol. 110・2

      Pages: 101-112

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Electron transfer chain reaction of the extracellular flavocytochrome cellobiose dehydrogenase from the basidiomycete phanerochaete chrysosporium2005

    • Author(s)
      Kiyohiko Igarashi et al.
    • Journal Title

      FEBS J. 272・11

      Pages: 2869-2877

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Inter-molecular electron transfer mechanism of the extracellular flavocytochrome cellobiose dehydrogenase from the basidiomycete Phanerochaete chrysosporium2005

    • Author(s)
      Kiyohiko Igarashi et al.
    • Journal Title

      Eur.J.Biochem. (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The crystal structure of xanthine oxidoreductase duing catalysis : Implications forreaction mechanism and enzyme inhibition2004

    • Author(s)
      Ken Okamoto, et al
    • Journal Title

      Proc.Natl.Acad.Sci.USA. 101・21

      Pages: 7931-7936

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Characterization and Molecular Cloning of Cellobiose Dehydrogenase from the Brown-Rot Fungus Coniophora puteana2004

    • Author(s)
      Taira Kajisa, et al
    • Journal Title

      Journal of Bioscience and Bioengineering 98・1

      Pages: 57-63

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Y-700[1-[3-Cyano-4-(2, 2dimethylpropoxy)pheny1]-1h-pyrazole-4-carboxylic Acid] : A Potent Xanthine Oxidoreductase Inhibitor with Hepatic Excretion2004

    • Author(s)
      Atsushi Fukunari, et al
    • Journal Title

      The Journal of Pharmacorogy and Experimental Therapeutics 311

      Pages: 519-528

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The Role of Active Site Glutamate Residues in Catalysis of Rhodobacter capsularus Xanthine Dehydrogenase2004

    • Author(s)
      Silke Leimkuhler, et al
    • Journal Title

      J.Biol.Chem. 279・39

      Pages: 40437-40444

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The crystal structure of xanthine oxidoreductase during catalysis : Implications forreaction mechanism and enzyme inhibition2004

    • Author(s)
      Ken Okamoto, et al
    • Journal Title

      Proc.Natl.Acad.Sci.USA. 101(21)

      Pages: 7931-7936

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Characterization and Molecular Cloning of Cellobiose Dehydrogenase from the Brown-Rot Fungus Coniophora puteana2004

    • Author(s)
      Taira Kajisa, et al
    • Journal Title

      Journal of Bioscience and Bioengineering 98(1)

      Pages: 57-63

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Y-700[1-[3-Cyano-4-(2,2dimethylpropoxy)phenyl]-1H-pyrazole-4-carboxylic Acid] : A Potent Xanthine Oxidoreductase Inhibitor with Hepatic Excretion2004

    • Author(s)
      Atsushi Fukunari, et al
    • Journal Title

      The Journal of Pharmacorogy and Experimental Therapeutics 311

      Pages: 519-528

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The Role of Active Site Glutamate Residues in Catalysis of Rhodobacter capsulatus Xanthine Dehydrogenase2004

    • Author(s)
      Silke Leimkuhler, et al
    • Journal Title

      J.Biol.Chem. 279(39)

      Pages: 40437-40444

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The crystal structure of xanthine oxidoreductase during catalysis: Implications for reaction mechanism and enzyme inhibition2004

    • Author(s)
      ken Okamoto et al.
    • Journal Title

      Proc.Natl.Acad.Sci.USA. 101・21

      Pages: 7931-7936

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Characterization and Molecular Cloning of Cellobiose Dehydrogenase from the Brown-Rot Fungus Coniophora puteana2004

    • Author(s)
      Taira kajisa et al.
    • Journal Title

      Journal of Bioscience and Bioengineering 98・1

      Pages: 57-63

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Y-700[1-[3-Cyano-4-(2,2dimethylpropoxy)phenyl]-1H-pyrazoie-4-carboxylic Acid]: A Potent Xanthine Oxidoreductase Inhibitor with Hepatic Excretion2004

    • Author(s)
      Atsushi Fukuanri et al.
    • Journal Title

      The Journal of Pharmacorogy and Experimental Therapeutics 311

      Pages: 519-528

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The Role of Active Site Glutamate Residues in Catalysis of Rhodobacter capsulatus Xanthine Dehydrogenase2004

    • Author(s)
      Silke Leimkuhler et al.
    • Journal Title

      J.Biol.Chem. 279・39

      Pages: 40437-40444

    • Related Report
      2004 Annual Research Report
  • [Journal Article] キサンチン脱水素酵素から酸化酵素への蛋白質構造・機能の変換の分子機構2004

    • Author(s)
      岡本 研, 他
    • Journal Title

      蛋白質 核酸 酵素 49・5

      Pages: 625-633

    • Related Report
      2004 Annual Research Report
  • [Presentation] キサンチンオキシダーゼによる活性酸素の生成機構2008

    • Author(s)
      西野武士
    • Organizer
      第15回マクロライド新作用研究会
    • Place of Presentation
      東京
    • Year and Date
      2008-07-12
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Mechanism of formation of active oxygen species by xanthine oxidoreductase2008

    • Author(s)
      Takeshi Nishino
    • Organizer
      The 15^<th> meeting for newly found effect of macrolide drug
    • Place of Presentation
      Tokyo
    • Year and Date
      2008-07-12
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] New Application of Xanthine Oxidoreductase Inhibitors2008

    • Author(s)
      Takeshi Nishino
    • Organizer
      16^<th> International Symposioum on Flavins and Flavoproteins
    • Place of Presentation
      スペイン
    • Year and Date
      2008-06-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] New Application of Xanthine Oxidoreductase Inhibitors2008

    • Author(s)
      Takeshi Nishino
    • Organizer
      16^<th> International Symposium on Flavins and Flavoproteins
    • Place of Presentation
      Spain
    • Year and Date
      2008-06-08
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 抗痛風薬の1つの利用法を例に本学会を考える2008

    • Author(s)
      西野武士
    • Organizer
      第41回日本痛風・核酸代謝学会
    • Place of Presentation
      福井
    • Year and Date
      2008-02-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [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
      第41回日本痛風・核酸代謝学会
    • Place of Presentation
      福井
    • Year and Date
      2008-02-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Insight into the significance of the society.A new therapeutic usage of anti-gout drugs2008

    • Author(s)
      Takeshi Nishino
    • Organizer
      41^<th> Annual meeting for gout and nucleic acid metabolism
    • Place of Presentation
      Fukui
    • Year and Date
      2008-02-14
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Structure basis for mechanism of inhibition of xanthine oxidoreductase2008

    • Author(s)
      Ken Okamoto
    • Organizer
      41^<th> Annual meeting for gout and nucleic acid metabolism
    • Place of Presentation
      Fukui
    • Year and Date
      2008-02-14
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] キサンチン酸化還元酵素のミリブデン反応中心の構造:基質・阻害剤認識と反応機構2007

    • Author(s)
      西野武士
    • Organizer
      第45回日本生物物理学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-21
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] 哺乳類のキサンチン脱水素酵素とバクテリア由来のキサンチン脱水素酵素との間における動的構造の差異2007

    • Author(s)
      菊地浩人
    • Organizer
      第45回日本生物物理学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-21
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] the structure of the molybdenum center, mechanism of molecular recognition of substrate & inhibitors, and hydroxylation reaction2007

    • Author(s)
      Takeshi Nishino
    • Organizer
      45^<th> Annual Meeting of Japanese Biophysical Society
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-12-21
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Difference in molecular dynamics between bacterial and mammalian xanthine dehydrogenases2007

    • Author(s)
      Hiroto Kikuchi
    • Organizer
      45^<th> Annual Meeting of Japanese Biophysical Society
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-12-21
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] キサンチン酸化還元酵素の基質結合様式と周囲残基の機能2007

    • Author(s)
      岡本 研
    • Organizer
      第80回日本生化学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-11
    • Related Report
      2007 Annual Research Report
  • [Presentation] ヒトキサンチン酸化還元酵素の構造解析2007

    • Author(s)
      松村 智裕
    • Organizer
      第80回日本生化学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-11
    • Related Report
      2007 Annual Research Report
  • [Presentation] キサンチン脱水素酵素酸化酵素の変換機構/C末ペプチドの役割2007

    • Author(s)
      西野 朋子
    • Organizer
      第80回日本生化学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-11
    • Related Report
      2007 Annual Research Report
  • [Presentation] キサンチン脱水素酵素-酸化酵素変換の役割2007

    • Author(s)
      李 頴
    • Organizer
      第80回日本生化学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-11
    • Related Report
      2007 Annual Research Report
  • [Presentation] ラットヘム結合蛋白質HBP23の多量体形成機構の解析2007

    • Author(s)
      阿部 靖子
    • Organizer
      第80回日本生化学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-11
    • Related Report
      2007 Annual Research Report
  • [Presentation] Ligand Binding Structures of Mammalian Xanthine Oxidoreductase : Implications for Hydroxylation Mechanism.2007

    • Author(s)
      Ken Okamoto
    • Organizer
      Goodon Research Conferences(Molybdenum & Tungstem Enzymes)
    • Place of Presentation
      アメリカ
    • Year and Date
      2007-07-01
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Crystal Structure of Human Xanthine Oxidoreductase2007

    • Author(s)
      Tomohiro Matsumura
    • Organizer
      Goodon Research Conferences(Molybdenum & Tungstem Enzymes)
    • Place of Presentation
      アメリカ
    • Year and Date
      2007-07-01
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Ligand Binding Structures of Mammalian Xanthine Oxidoreductase : Implications for Hydroxylation Mechanism2007

    • Author(s)
      Ken Okamoto
    • Organizer
      Gordon Research Conferences(Molybdenum & Tungsten Enzymes)
    • Place of Presentation
      U.S.A
    • Year and Date
      2007-07-01
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Crystal Structure of Human Xanthine Oxidoreductase2007

    • Author(s)
      Tomohiro Matsumura
    • Organizer
      Gordon Research Conferences(Molybdenum & Tungsten Enzymes)
    • Place of Presentation
      U.S.A
    • Year and Date
      2007-07-01
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Ligand Binding Structures of Mammalian Xanthine Oxidoreductase: Implications for Hydroxylation Mechanism.2007

    • Author(s)
      Ken Okamoto
    • Organizer
      Gordon Research Conferences(Molybdenum & Tungsten Enzymes)
    • Place of Presentation
      アメリカ ニューロンドン
    • Year and Date
      2007-07-01
    • Related Report
      2007 Annual Research Report
  • [Presentation] Crystal Structure of Human Xanthine Oxidoreductase2007

    • Author(s)
      Tomohiro Matsumura
    • Organizer
      Gordon Research Conferences(Molybdenum & Tungsten Enzymes)
    • Place of Presentation
      アメリカ ニューロンドン
    • Year and Date
      2007-07-01
    • Related Report
      2007 Annual Research Report
  • [Presentation] The Molecular Mechanism of Transition from Xanthine Dehydrogenase to Xanthine Oxidase2007

    • Author(s)
      Takeshi Nishino
    • Organizer
      12th International Symposiumj on Purine and Pyrimidine Metabolism in Man
    • Place of Presentation
      アメリカ
    • Year and Date
      2007-06-24
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Potent inhibiors of xanthine oxidoreductase : Mechansims of inhibition and crystal structures of the enzyme-inhibitor complexes2007

    • Author(s)
      Ken Okamoto
    • Organizer
      12th International Symposiumj on Purine and Pyrimidine Metabolism in Man
    • Place of Presentation
      アメリカ
    • Year and Date
      2007-06-24
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Mutatioanl Analysis of Human Xanthine Oxidase : Roles of the Amino Acid Residues around the Active Site in Purine Oxidation Reaction2007

    • Author(s)
      Tomohiro Matsumura
    • Organizer
      12th International Symposiumj on Purine and Pyrimidine Metabolism in Man
    • Place of Presentation
      アメリカ
    • Year and Date
      2007-06-24
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The Molecular Mechanism of Transition from Xanthine Dehydrogenase to Xanthine Oxidase2007

    • Author(s)
      Takeshi Nishino
    • Organizer
      12th International Symposium on Purine and Pyrimidine Metabolism in Man
    • Place of Presentation
      U.S.A
    • Year and Date
      2007-06-24
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Potent inhibitors of xanthine oxidoreductase : Mechansims of inhibition and crystal structures of the enzyme-inhibitor complexes2007

    • Author(s)
      Ken Okamoto
    • Organizer
      12th International Symposium on Purine and Pyrimidine Metabolism in Man
    • Place of Presentation
      U.S.A
    • Year and Date
      2007-06-24
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Mutational Analysis of Human Xanthine Oxidase : Roles of the Amino Acid Residues around the Active Site in Purine Oxidation Reaction2007

    • Author(s)
      Tomohiro Matsumura
    • Organizer
      12th International Symposium on Purine and Pyrimidine Metabolism in Man
    • Place of Presentation
      U.S.A
    • Year and Date
      2007-06-24
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The Molecular Mechanism of Transition from Xanthine Dehydrogenase to Xanthine Oxidase2007

    • Author(s)
      Takeshi Nishino
    • Organizer
      12th International Symposium on Purine and Pyrimidine Metabolism in Man
    • Place of Presentation
      アメリカ シカゴ
    • Year and Date
      2007-06-24
    • Related Report
      2007 Annual Research Report
  • [Presentation] Potent inhibitors of xanthine oxidoreductase: Mechansims of inhibition and crystal structures of the enzyme-inhibitor complexes2007

    • Author(s)
      Ken Okamoto
    • Organizer
      12th International Symposium on Purine and Pyrimidine Metabolism in Man
    • Place of Presentation
      アメリカ シカゴ
    • Year and Date
      2007-06-24
    • Related Report
      2007 Annual Research Report
  • [Presentation] Mutational Analysis of Human Xanthine Oxidase: Roles of the Amino Acid Residues around the Active Site in Purine Oxidation Reaction2007

    • Author(s)
      Tomohiro Matsumura
    • Organizer
      12th International Symposium on Purine and Pyrimidine Metabolism in Man
    • Place of Presentation
      アメリカ シカゴ
    • Year and Date
      2007-06-24
    • Related Report
      2007 Annual Research Report
  • [Presentation] 新旧高尿酸血症の治療薬2007

    • Author(s)
      西野武士
    • Organizer
      第40回日本痛風・核酸代謝学会
    • Place of Presentation
      東京
    • Year and Date
      2007-02-15
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Old and new therapeutic drugs of anti-hyper uricemia2007

    • Author(s)
      Takeshi Nishino
    • Organizer
      40^<th> Annual meeting for gout and nucleic acid metabolism
    • Place of Presentation
      Tokyo
    • Year and Date
      2007-02-15
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Difference in the dynamic structure between mannalian and bacterial xanthine oxidoredutases2006

    • Author(s)
      Hiroto Kikuchi
    • Organizer
      Fifth East Asian Biophysics Symposium & Forty-fourth Annual Meeting of the Biophysical Society of Japan
    • Place of Presentation
      沖縄
    • Year and Date
      2006-11-12
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Difference in the dynamic structure between mammalian and bacterial xanthine oxidoreductases2006

    • Author(s)
      Hiroto Kikuchi
    • Organizer
      Fifth East Asian Biophysics Symposium & Forty-fourth Annual Meeting of the Biophysical Society of Japan
    • Place of Presentation
      in Okinawa
    • Year and Date
      2006-11-12
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] タンパク質の形と創薬2006

    • Author(s)
      西野武士
    • Organizer
      日本生化学会関東支部例会
    • Place of Presentation
      新潟
    • Year and Date
      2006-10-06
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Protein shape and drug design2006

    • Author(s)
      Takeshi Nishino
    • Organizer
      The Kanto-area Meeting of Japanese Biochemical Society
    • Place of Presentation
      Niigata
    • Year and Date
      2006-10-06
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] モリブドプテリン含有フラビン酵素であるキサンチン酸化還元酵素の構造・反応機構・調節機構と生理的意義2006

    • Author(s)
      西野武士
    • Organizer
      第20回プテリジンコンファレンス&第14回サイトカイン・ネオプテリン研究会第2回連合研究発表会
    • Place of Presentation
      東京
    • Year and Date
      2006-07-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Xanthine oxidase, a molybdopterin containing flavoprotein : structure, reaction mechanism regulation and physiological significance2006

    • Author(s)
      Takeshi Nishino
    • Organizer
      The 2^<nd> bound meeting of 2oth pterin society and 14^<th> cytokine and neopterin research organization
    • Place of Presentation
      Tokyo
    • Year and Date
      2006-07-08
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 複合反応中心を持つ複合金属フラビン酵素の発現と精製と結晶化2006

    • Author(s)
      西野武士
    • Organizer
      第6回蛋白質科学会年会
    • Place of Presentation
      京都
    • Year and Date
      2006-04-24
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Purification and crystallization of complex flavoprotein having multiple reaction centers2006

    • Author(s)
      Takeshi Nishino
    • Organizer
      The 6^<th> Annual Meeting of Protein Science
    • Place of Presentation
      Kyoto
    • Year and Date
      2006-04-24
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The Mammalian Xanthine Oxidoreductase : Mechanisms of Hydroxylation Reaction and Dehyrogenase/Oxidase Conversion2006

    • Author(s)
      Takeshi Nishino
    • Organizer
      武田科学振興財団シンポジウム
    • Place of Presentation
      京都
    • Year and Date
      2006-04-10
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The Mammalian Xanthine Oxidoreductase : Mechanisms of Hydroxylation Reaction and Dehydrogenase/Oxidase Conversion2006

    • Author(s)
      Takeshi Nishino
    • Organizer
      Takeda Foundation for Scientific Reseach
    • Place of Presentation
      Kyoto
    • Year and Date
      2006-04-10
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 種々の高尿酸血症治療薬をめざした阻害剤と蛋白質の複合体結晶構造解析から学ぶこと2006

    • Author(s)
      西野武士
    • Organizer
      第3回産学連携フォーラム
    • Place of Presentation
      東京
    • Year and Date
      2006-02-22
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Lessons from the crystal structures of the XOR protein bound with various inhibitors designed for anti-hyper uricemia2006

    • Author(s)
      Takeshi Nishino
    • Organizer
      The 3rd Forum for Cooperation within Academy and Industry
    • Place of Presentation
      Tokyo
    • Year and Date
      2006-02-22
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 新規尿酸生成阻害剤を用いた治療戦略2006

    • Author(s)
      西野武士
    • Organizer
      第39回日本痛風・核酸代謝学会
    • Place of Presentation
      京都
    • Year and Date
      2006-02-09
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Therapeutic strategy with new drug against uric acid generation2006

    • Author(s)
      Takeshi Nishino
    • Organizer
      39^<th> Annual meeting for gout and nucleic acid metabolism
    • Place of Presentation
      Kyoto
    • Year and Date
      2006-02-09
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] モリブデン配位子構造とキサンチン水酸化と機構2005

    • Author(s)
      西野武士
    • Organizer
      研究会「分子系の構造と電子状態」
    • Place of Presentation
      SPring-8
    • Year and Date
      2005-09-07
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Structure of molybdenum ligands and mechanism of xanthine hydroxylation2005

    • Author(s)
      Takeshi Nishino
    • Organizer
      Structure and electronic state in molecular system
    • Place of Presentation
      Hyogo(SPring-8)
    • Year and Date
      2005-09-07
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Mechanism of molybdenum-dependent hydroxylation : Crystal structure of reaction intermediate and roles of amino acid residues in the molybdenum active site2005

    • Author(s)
      Takeshi Nishino
    • Organizer
      Gordon Research Conference
    • Place of Presentation
      イギリス
    • Year and Date
      2005-07-09
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Mechanism of molybdenum-dependent hydroxylation : Crystal structure of reaction intermediate and roles of amino acid residues in the molybdenum active site2005

    • Author(s)
      Takeshi Nishino
    • Organizer
      Gordon Research Conference
    • Place of Presentation
      U.K
    • Year and Date
      2005-07-05
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] HANDBOOK OF METALLOPROTEINS2008

    • Author(s)
      Takeshi Nishino, Emil F.Pai
    • Total Pages
      14
    • Publisher
      Wiley
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] FLAVINS AND FLAVOPROTEINS 20052005

    • Author(s)
      Ken Okamoto, et al
    • Total Pages
      12
    • Publisher
      ARchiTect.Inc.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] FLAVINS AND FLAVOPROTEINS 20052005

    • Author(s)
      Kiyohiko Igarashi, et al.
    • Total Pages
      4
    • Publisher
      ARchiTect.Inc.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] FLAVINS AND FLAVOPROTEINS 20052005

    • Author(s)
      Shiro Kondo, et al.
    • Total Pages
      4
    • Publisher
      ARchiTect.Inc.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] FLAVINS AND FLAVOPROTEINS 20052005

    • Author(s)
      Atsushi Fukunari, et al.
    • Total Pages
      6
    • Publisher
      ARchiTect.Inc.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] The Mammalian Xanthine Oxidoreductase : Mechanisms of Hydroxylation Reaction and Dehydrogenase/Oxidase Conversion (FLAVINS AND FLAVOPROTEINS 2005)2005

    • Author(s)
      Ken Okamoto et al.
    • Total Pages
      12
    • Related Report
      2005 Annual Research Report
  • [Book] Electron Transfer Chain Reaction of Celobiose Dehydrogenase from the Basidiomycete Phanerochaete chrysosporium (FLAVINS AND FLAVOPROTEINS 2005)2005

    • Author(s)
      Kiyohiko Igarashi et al.
    • Total Pages
      4
    • Related Report
      2005 Annual Research Report
  • [Book] Febuxostat, a Novel Non-Purine Selective Inhibitor of Xanthine Oxidase -Mechanism of Action and Clinical Application- (FLAVINS AND FLAVOPROTEINS 2005)2005

    • Author(s)
      Shiro Kondo et al.
    • Total Pages
      4
    • Related Report
      2005 Annual Research Report
  • [Book] Mechanism of Xanthine Oxidoreductase Inhibition by Y-700 and its Hypouricemic Effect in Humans (FLAVINS AND FLAVOPROTEINS 2005)2005

    • Author(s)
      Atsushi Fukunari et al.
    • Total Pages
      6
    • Related Report
      2005 Annual Research Report
  • [Patent(Industrial Property Rights)] 筋萎縮性側索硬化症治療薬2007

    • Inventor(s)
      西野武士, 阿部靖子, 加藤信介
    • Industrial Property Rights Holder
      日本医科大学・鳥取大学
    • Filing Date
      2007-07-13
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Overseas

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Published: 2004-04-01   Modified: 2016-04-21  

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