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Density Functional Theory Approach to Biochemical Reactions

Research Project

Project/Area Number 14390039
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 広領域
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

YOSHIZAWA Kazunari  Kyushu University, Institute for Materials Chemistry and Engineering, Processor, 先導物質化学研究所, 教授 (30273486)

Co-Investigator(Kenkyū-buntansha) SHIOTA Yoshihito  Kyushu University, Institutee for Materials Chemistry and Engineering, Research Associate, 先導物質化学研究所, 助手 (70335991)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥10,700,000 (Direct Cost: ¥10,700,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2003: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥5,200,000 (Direct Cost: ¥5,200,000)
KeywordsDensity functional theory / Metalloenzyme / Cytochrome p450 / Methane monooxygenase / Heme oxygenase / トラジェクトリ法
Research Abstract

Mechanistic and energetic aspects for the conversion of camphor to 5-exo-hydroxycamphor by the compound I iron-oxo species of cytochrome P450 are discussed from B3LYP DFT calculations. This reaction occurs in a two-step manner along the lines that the oxygen rebound mechanism suggests. The activation energy for the first transition state of the H-atom abstraction at the C5 atom of camphor is computed to be more the 20 kcal/mol. This H-atom abstraction is the rate-determining step in this hydroxylation reaction, leading to a reaction intermediate that involves a carbon radical species and the iron hydroxo species. The second transition state of the rebound step that connects the reaction intermediate and the product alcohol complex lies a few kcal/mol below that for the H-atom abstraction on the doublet and quartet potential energy surfaces. This energetic feature allows the virtually barrierless recombination in both spin states, being consistent with experimentally observed high stere … More oselectivity and brief lifetimes of the reaction intermediate. The overall energetic profile of the catalytic mechanism of camphor hydroxylation particularly with respect to why the high activation energy for the H-atom abstraction is accessible under physiological conditions is also considered and calculated. According to a proton source model involving Thr252,Asp251, and two solvent water molecules, the energetics for the conversion of the iron-peroxo species to compound I is studied. A significant energy over 50 kcal/mol is released in the course of this dioxygen activation process. Dopamine hydroxylation by the copper-superoxo, -hydroperoxo, and -oxo species of dopamine β-monooxygenase(DBM) is investigated from theoretical calculations to identify the active species in its reaction and to reveal the key functions of the surrounding amino acid residues in substrate binding. A 3D model of rat DBM is constructed by homology modeling using the crystal structure of peptidylglycine α-hydroxylating monooxygenase(PHM) with a high sequence identity of 30% as a template. In the constructed 3D model, the CuA site in domain 1 is coordinated by three histidine residues, His265, His266, and His336, while the CuB site in domain 2 is coordinated by two histidine residues, His415 and His417, and by a methionine residue Met490. The three Glu268, Glu369, and Tyr494 residues are suggested to play an important role in the substrate binding at the active site of DBM to enable the stereospecific hydrogen-atom abstraction. Quantum mechanical/molecular mechanical (QM/MM) calculations are performed to determine the structure and catalytic mechanism of the copper-superoxo, -hydroperoxo, and -oxo species in the whole-enzyme model with about 4,700 atoms. The reactivity of the copper-oxo species is significant from calculations of the whole-enzyme model. Less

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (29 results)

All 2004 2003 Other

All Journal Article (16 results) Book (1 results) Publications (12 results)

  • [Journal Article] How Heme Metabolism Occurs in Heme Oxygenase : Computational Study of Oxygen Donation Ability of the Oxo and Hydroperox2004

    • Author(s)
      T.Kamachi
    • Journal Title

      Journal of the American Chemical Society 126

      Pages: 3672-3673

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A Vibrational Analysis on Possible Peroxo Forms of Soluble Methane Monooxygenase2004

    • Author(s)
      T.Yumura
    • Journal Title

      Bulletin of the Chemical Society of Japan 77

      Pages: 1305-1311

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] QM/MM Study of the Mononuclear Non-heme Iron Active Site of Phenyl alanine Hydroxylase2004

    • Author(s)
      Y.Shiota
    • Journal Title

      Journal of Physical Chemistry B 108

      Pages: 17226-17237

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Catalytic Roles of the Active Site Aminoacid Residues of Coenzyme B12-Dependent Diol Dehydratase2004

    • Author(s)
      T.Kamachi
    • Journal Title

      Journal of the American Chemical Society 126

      Pages: 16207-16216

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Highly Versatile Organostibine Mediators for Living Radical Polymerization2004

    • Author(s)
      S.Yamago
    • Journal Title

      Journal of the American Chemical Society 126

      Pages: 13908-13909

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Theoretical Study of Thermal Isomerization of Silacyclobutene to Cyclopropene2004

    • Author(s)
      Y.Shiota
    • Journal Title

      Organometallics 23

      Pages: 4744-4749

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] How Heme Metabolism Occurs in Heme Oxygenase : Computational Study of Oxygen Donation Ability of the Oxo and Hydroperoxo Species2004

    • Author(s)
      T.Kamachi, A.F.Shestakov, K.Yoshizawa
    • Journal Title

      Journal of the American Chemical Society 126

      Pages: 3672-3673

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Highly Versatile Organostibine Mediators for Living Radical Polymerization2004

    • Author(s)
      S.Yamago, B.Ray, K.Iida, J.Yoshida, T.Tada, K.Yoshizawa, Y.Kwak, A.Goto, T.Fukuda
    • Journal Title

      Journal of the American Chemical Society 126

      Pages: 13908-13909

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Catalytic Roles of the Active Site Aminoacid Residues of Coenzyme B12-Dependent Diol Dehydratase : A Quantum Mechanical/Molecular Mechanical Study2004

    • Author(s)
      T.Kamachi, T.Toraya, K.Yoshizawa
    • Journal Title

      Journal of the American Chemical Society 126

      Pages: 16207-16216

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] QM/MM Study of the Mononuclear Non-heme Iron Active Site of Phenylalanine Hydroxylase2004

    • Author(s)
      Y.Shiota, K.Yoshizawa
    • Journal Title

      Journal of Physical Chemistry B 108

      Pages: 17226-17237

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A Vibrational Analysis on Possible Peroxo Forms of Soluble Methane Monooxygenase2004

    • Author(s)
      T.Yumura, K.Yoshizawa
    • Journal Title

      Bulletin of the Chemical Society of Japan 77

      Pages: 1305-1311

    • NAID

      10013278660

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Theoretical Study of Thermal Isomerization of Silacyclobutene to Cyclopropene2004

    • Author(s)
      Y.Shiota, M.Yasunaga, A.Naka, M.Ishikawa, K.Yoshizawa
    • Journal Title

      Organometallics 23

      Pages: 4744-4749

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] How Heme Metabolism Occurs in Heme Oxygenase : Computational Study Oxygen Donation Ability of the Oxo and Hydroperox2004

    • Author(s)
      T.Kamachi
    • Journal Title

      Journal of the American Chemical Society 126

      Pages: 3672-3673

    • Related Report
      2004 Annual Research Report
  • [Journal Article] QM/MM Study of the Mononuclear Non-heme Iron Active Site of Phenylalanine Hydroxylase2004

    • Author(s)
      Y.Shiota
    • Journal Title

      Journal of Physical Chemistry B 108

      Pages: 17226-17237

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A Theoretical Study on the Mechanism of Camphor Hydroxylation by Compound I of Cytochrome P4502003

    • Author(s)
      T.Kamachi, K.Yoshizawa
    • Journal Title

      Journal of the American Chemical Society 125

      Pages: 4652-4661

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A Non-Radical Mechanism for Methane Hydroxylation at the Diiron Active Site of Soluble Methane Monooxygenase2003

    • Author(s)
      K.Yoshizawa, T.Yumura
    • Journal Title

      Chemistry -A European Journal 9

      Pages: 2347-2358

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 化学結合の基礎2004

    • Author(s)
      吉澤
    • Total Pages
      155
    • Publisher
      化学同人
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Publications] Y.Shiota, K.Yoshizawa: "A Spin-Orbit Coupling Study on the Spin Inversion Processes in the Direct Methane-to-Methanol Conversion by FeO^+"Journal of Chemical Physics. 118. 5872-5879 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Yoshizawa et al.: "Does the Hydroperoxo Species of Cytochrome P450 Participate in Olefin Epoxidation with the Main Oxidant, Compound I? Criticism from Density Functioanl Theory Calculations"Bulletin of the Chemical Society of Japan. 76. 721-732 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] T.kamachi, K.Yoshizawa: "A Theoretical Study on the Mechanism of Camphor Hydroxylation by Compound I of Cytochrome P450"Journal of the American Chemical Society. 125. 4652-4661 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Yoshizawa, T.Yumura: "A Non-Radical Mechanism for Methane Hydroxylation at the Diiron Active Site of Soluble Methane Monooxygenase"Chemistry-A European Journal. 9. 2347-2358 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Yoshizawa et al.: "A Theoretical Study of Reactivity and Regioselectivity in the Hydroxylation of Adamantane by Ferrate(VI)"Journal of Organic Chemistry. 68. 3958-3965 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Yoshizawa et al.: "Mechanistic Proposals for Direct Benzene Hydroxylation over Fe-ZSM-5 Zeolite"Journal of Physical Chemistry B. 107. 11404-11410 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] T.Yumura: "Mechanism for the Formaldehyde to Formic Acid and the Formic Acid to Carbon Dioxide Conversious Mediated by FeO^+"J.Phy.Chem.B. 106. 621-630 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Yoshizawa: "Theoretical Study on Kinetic Isotope Effects in the C-H Bond Activation of Alkanes by Iron-Oxo Species"Coord.Chem.Rev.. 226. 251-259 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Eda: "Theoretical Predictions on the Mechanism of Catalysis of Coenzyme B_<12>-Dependent Diol Dehydratase"Bull.Chem.Soc.Jpn.. 75. 1469-1481 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Yoshizawa: "A Non-Radical Mechanism for Methane Hydroxylation at the Diiron Active Site of Soluble Methane Monooxygenase"Chem.Eur.J.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Kamachi: "A Theoretical Study on the Mechanism of Camphor Hydroxylation by Compound I of Cytochrome P450"J.Am.Chem.Soc.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Yoshizawa: "量子生物無機化学のすすめ"化学. 57・10. 18-22 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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