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Multidimensional energy analysis of pyridoxal-enzyme and quinoenzyme reactions

Research Project

Project/Area Number 21570120
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Structural biochemistry
Research InstitutionOsaka Medical College

Principal Investigator

HAYASHI Hideyuki  大阪医科大学, 医学部, 教授 (00183913)

Co-Investigator(Kenkyū-buntansha) TAKESHI Murakawa  大阪医科大学, 医学部, 助教 (90445990)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsプロトン移動 / ピリドキサール酵素 / キノン酵素 / 反応機構 / エネルギー準位 / セリンパルミトイル転移酵素 / トレオニン合成酵素 / 銅アミン酸化酵素 / 立体化学 / 酵素反応機構 / 遷移相速度論 / X線結晶解析 / ピリドキサールリン酸 / タンパク質のゆらぎ / 計算化学 / エネルギー進位
Research Abstract

Multidimensional free energy analysis of the reactions of the catalytic reactions of two pyridoxal enzymes(serine palmitoyltransferase and threonine synthase) and a quinoenzyme cupper amine oxidase were carried out to elucidate the energetic mechanism of these enzymes. The mechanisms by which the versatile catalyst pyridoxal phosphate is organized to catalyze only one type of reaction, i. e., a stereochemical mechanism and the product-assisted catalysis, were clarified. Analysis of the reaction of cupper amine oxidase, together with the ultra-high-resolution structure of the enzyme, revealed that the dynamic motion of the enzyme provides the basis for the quantum tunneling effect that promotes its catalysis.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (22 results)

All 2012 2011 2010 2009

All Journal Article (13 results) (of which Peer Reviewed: 7 results) Presentation (9 results)

  • [Journal Article] Structural insights into the substrate specificity of bacterial copper amine oxidase obtained by using irreversible inhibitors2012

    • Author(s)
      Murakawa T, Hayashi H, Taki M, Yamamoto Y, Kawano Y, Tanizawa K, Okajima T.
    • Journal Title

      J Biochem

      Volume: 151 Pages: 167-178

    • NAID

      10031166055

    • Related Report
      2011 Final Research Report
  • [Journal Article] Structural insights into the substrate specificity of bacterial copper amine oxidase obtained by using irreversible inhibitors2012

    • Author(s)
      Hideyuki Hayashi, Takeshi Murakawa
    • Journal Title

      J.Biochem.

      Volume: 151 Issue: 2 Pages: 167-178

    • DOI

      10.1093/jb/mvr125

    • NAID

      10031166055

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of a conserved arginine residue during catalysis in serine palmitoyltransferase2011

    • Author(s)
      Lowther, J., Charmier, G., Raman, M. C., Ikushiro, H., Hayashi, H., Campopiano, D. J.
    • Journal Title

      FEBS Lett

      Volume: 585 Pages: 1729-1734

    • Related Report
      2011 Final Research Report
  • [Journal Article] Product-assisted catalysis as the basis of the reaction specificity of threonine synthase2011

    • Author(s)
      Murakawa, T., Machida, Y., Hideyuki Hayashi
    • Journal Title

      J. Biol. Chem

      Volume: 286 Pages: 2774-2784

    • Related Report
      2011 Final Research Report
  • [Journal Article] Analysis of mammalian histidine decarboxylase dimerization interface reveals an electrostatic hotspot important for catalytic site topology and function2011

    • Author(s)
      Moya-Garcia, A. A., Rodriguez-Agudo, D., Hayashi, H., Medina, M. A., Urdiales, J. L., Sanchez-Jimenez, F.
    • Journal Title

      J. Chem. Theory. Comput

      Volume: 7 Pages: 1935-1942

    • Related Report
      2011 Final Research Report
  • [Journal Article] Analysis of mammalian histidine decarboxylase dimerization interface reveals an electrostatic hotspot important for catalytic site topology and function2011

    • Author(s)
      Hideyuki Hayashi
    • Journal Title

      J.Chem.Theory Comput.

      Volume: 7 Issue: 6 Pages: 1935-1942

    • DOI

      10.1021/ct100690p

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of a conserved arginine residue during catalysis in serine palmitoyltransferase2011

    • Author(s)
      Hideyuki Hayashi
    • Journal Title

      FEBS Lett.

      Volume: 585 Issue: 12 Pages: 1729-1734

    • DOI

      10.1016/j.febslet.2011.04.013

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Product-assisted catalysis as the basis of the reaction specificity of threonine synthase2011

    • Author(s)
      Murakawa
    • Journal Title

      J.Biol.Chem.

      Volume: 286 Pages: 2774-2784

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reaction mechanism and molecular basis for selenium/sulfur discrimination of selenocysteine lyase2010

    • Author(s)
      Omi
    • Journal Title

      J.Biol.Chem.

      Volume: 285 Pages: 12133-12139

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multifunctional role of His159 in the catalytic reaction of serine palmitoyltransferase2009

    • Author(s)
      Shiraiwa, Y., Ikushiro, H., Hayashi, H.
    • Journal Title

      J. Biol. Chem

      Volume: Vol.284 Pages: 15487-15495

    • NAID

      110007730458

    • Related Report
      2011 Final Research Report
  • [Journal Article] Structural insights into the enzymatic mechanism of serine palmitoyltransferase from Sphingobacterium multivorum2009

    • Author(s)
      Ikushiro, H., Islam, M. M., Okamoto, A., Hoseki, J., Murakawa, T., Fujii, S., Miyahara, I., Hayashi, H.
    • Journal Title

      J Biochem

      Volume: 146 Pages: 549-562

    • NAID

      10026304060

    • Related Report
      2011 Final Research Report
  • [Journal Article] Multifunctional role of His159 in the catalytic reaction of serine palmitoyltransferase2009

    • Author(s)
      Shiraiwa, Yuka
    • Journal Title

      J.Biol.Chem. 284

      Pages: 15487-15495

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural insights into the enzymatic mechanism of serine palmitoyltransferase from Sphingobacterium multivorum2009

    • Author(s)
      Ikushiro, Hiroko
    • Journal Title

      J.Biochem. 146

      Pages: 549-562

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Acid-base chemistry of the catalytic reaction of the bacterial copper amine oxidase2011

    • Author(s)
      村川武志, 岡島俊英, 濱口章央, 谷澤克行, 林秀行
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都
    • Year and Date
      2011-09-22
    • Related Report
      2011 Final Research Report
  • [Presentation] Product-assisted catalysis is the basis of the reaction specificity of threonine synthase2011

    • Author(s)
      Hideyuki Hayashi
    • Organizer
      The Third International Conference on Cofactors
    • Place of Presentation
      University of Turku, Turku, Finland
    • Year and Date
      2011-07-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] 生成物支援触媒によってもたらされる酵素の反応特異性2011

    • Author(s)
      村川武志, 林秀行
    • Organizer
      第11回日本蛋白質科学会年会
    • Place of Presentation
      吹田
    • Year and Date
      2011-06-08
    • Related Report
      2011 Final Research Report
  • [Presentation] 銅含有アミン酸化酵素の触媒機構:酸化的半反応中間体の立体構造解析2010

    • Author(s)
      喜久川政吾, 岡島俊英, 濱口章央, 村川武志, 林秀行, 谷澤克行
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-07
    • Related Report
      2011 Final Research Report
  • [Presentation] トレオニン合成酵素の分光学的および速度論的解析2010

    • Author(s)
      村川武志, 林秀行
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-07
    • Related Report
      2011 Final Research Report
  • [Presentation] 銅アミン酸化酵素反応はトパセミキノンラジカル中間体を経由して進行する2009

    • Author(s)
      濱口章央, 岡島俊英, 谷澤克行, 村川武志, 林秀行
    • 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
      2011 Final Research Report
  • [Presentation] 速度論および構造解析に基づく酵素触媒反応におけるプロトントンネリング機構の解析2009

    • Author(s)
      村川武志, 岡島俊英, 谷澤克行, 林秀行
    • 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
      2011 Final Research Report
  • [Presentation] 銅アミン酸化酵素反応はトパセミキノンラジカル中間体を経由して進行する2009

    • Author(s)
      濱口章央
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド(兵庫)
    • Year and Date
      2009-10-22
    • Related Report
      2009 Annual Research Report
  • [Presentation] 速度論および構造解析に基づく酵素触媒反応におけるプロトントンネリング機構の解析2009

    • Author(s)
      村川武志
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド(兵庫)
    • Year and Date
      2009-10-22
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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