• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Control of Regioselectivity of Heme Oxygenase by Reconstruction of Hydrogen-Bonding Interactions between Substrate and Enzyme

Research Project

Project/Area Number 16350094
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemistry related to living body
Research InstitutionNational Institutes of Natural Sciences

Principal Investigator

FUJII Hiroshi  National Institutes of Natural Sciences, Okazaki Institute for Integrative Bioscience, Associate Professor, 岡崎統合バイオサイエンスセンター, 准教授 (80228957)

Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥15,600,000 (Direct Cost: ¥15,600,000)
Fiscal Year 2006: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2005: ¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 2004: ¥5,600,000 (Direct Cost: ¥5,600,000)
KeywordsArtificial enzyme / Chemoselectivity / Function alteration / Heme oxygenase / Oxygen activation / Heme
Research Abstract

Regioselective reactions catalyzed by enzymes are very important biologically and chemically. Therefore, molecular mechanisms of regioselective reactions have been studied for various enzymes with various spectroscopic methods. We have studied the molecular mechanism of heme oxygenase (HO), which catalyzes regioselective degradation of heme (iron protoporphyrinIX) to α-biliverdin, CO, and free iron ion. Interestingly, HO regiospecifically oxidize the α-meso position of the heme to form α-biliverdin isomer while non-enzymatic heme degradation forms all four possible α, β, γ, δ-biliverdin isomers at nearly identical yield. We have found two essential amino acid residues, Asp-140 and Arg-183 in rat-HO, for the a-regioselective heme degradation. We showed that the Asp-140 and Arg-183 residues control oxygen activation process and the substate (heme) binding process via hydrogen-bonding interactions, respectively. With combination of the Asp-140 and Arg-183 residues, the a-meso position of the heme is placed at the nearest position from the activated oxygen species, resulting in the a-regioselective reaction. This mechanism let us imagine that we can switch the regioselectivity of HO if we can control an orientation of the heme in HO so that the other meso position is placed at the nearest position from the activated oxygen species. To realize this idea, on the basis of the crystal structure of the wild type HO, we designed a mutant, in which the other meso position is placed at the nearest position from the activated oxygen species. In this project, we succeeded in conversion of α-selective HO to δ-selective HO with the present strategy. Furthermore, we also succeeded in controlling heme orientation in HO with mutation of amino acid residues, which results in β-selective and δ-selective HO.

Report

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

    (7 results)

All 2006 2005 2004

All Journal Article (7 results)

  • [Journal Article] ^<13>C and ^<15>N NMR Studies of Iron-Bound Cyanides of Heme proteins and related model complexes : Sensitive Probe for Detecting Hydrogen Bonding Interactions at the Proximal and Distal Sides2006

    • Author(s)
      Hiroshi Fujii
    • Journal Title

      Inorg. Chem. 45

      Pages: 6816-6827

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] ^<13>C and ^<15>N NMR Studies of Iron-Bound Cyanides of Heme proteins and related model complexes : Sensitive Probe for Detecting Hydrogen Bonding Interactions at the Proximal and Distal Sides2006

    • Author(s)
      Hiroshi Fujii
    • Journal Title

      Inorg.Chem. 45

      Pages: 6816-6827

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] ^<13>C and ^<13>N NMR Studies of Iron-Bound Cyanides of Heme proteins and related model complexes : Sensitive Probe for Detecting Hydrogen Bonding Interactions at the Proximal and Distal Sides2006

    • Author(s)
      Hiroshi Fujii
    • Journal Title

      Inorg.Chem. 45

      Pages: 6816-6827

    • Related Report
      2006 Annual Research Report
  • [Journal Article] O_2- and H_2O_2-dependent Verdoheme Degradation by Heme Oxygenase. Reaction Mechanisms and Potential Physiological Roles of The Dual Pathway Degradation2005

    • Author(s)
      T.Matsui
    • Journal Title

      J. Biol. Chem. 280

      Pages: 36833-36840

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] O_2-and H_2O_2-dependent Verdoheme Degradation by Heme Oxygenase. Reaction Mechanisms and Potential Physiological Roles of The Dual Pathway Degradation2005

    • Author(s)
      T.Matsui
    • Journal Title

      J.Biol.Chem. 280

      Pages: 36833-36840

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] O_2- and H_2O_2 -dependent Verdoheme Degradation by Heme Oxygenase. Reaction Mechanisms and Potential Physiological Roles of The Dual Pathway Degradation2005

    • Author(s)
      T.Matsui
    • Journal Title

      J.Biol.Chem. 280

      Pages: 36833-36840

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Essential Amino Acid Residues Controlling the Unique Regioselectivity of Heme Oxygenase in Psudomonas aeruginosa2004

    • Author(s)
      Hiroshi Fujii
    • Journal Title

      J.Am.Chem.Soc. 126

      Pages: 4466-4467

    • Related Report
      2004 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi