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Relation between the structure and the oxygen acitivation of heme oxygenase reaction

Research Project

Project/Area Number 12680625
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionYAMAGATA UNIVERSITY

Principal Investigator

YOSHIDA Tadashi  YAMAGATA UNIVERSIY SCHOOL OF MEDICINE, DEPARTMENT OF BIOCHEMISTRY, PROFESSOR, 医学部, 教授 (10004673)

Co-Investigator(Kenkyū-buntansha) FUJII Hiroshi  INSTITUTE FOR MOLECULAR SCIENCE, ASSOCIATE PROFESSOR, 分子科学研究所, 助教授 (80228957)
ZHANG Xuhong  YAMAGATA UNIVERSIY SCHOOL OF MEDICINE, DEPARTMENT OF BIOCHEMISTRY, INSTRUCTOR, 医学部, 助手 (10292442)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsHEME OXYGENASE / OXYGEN ACTIVATION / HEME DEGRADATION / INTERMEDIARY STEP / BILIVERDIN REDUCTASE / BILIVERDIN / BILIRUBIN / 酸素活性化機構 / ヘムの分解 / CO / 細菌のヘム分解酵素 / Hmu O / 酵素活性化機構 / ピリペルジン / ピリルビン
Research Abstract

(1)The hemin complex of HmuO, a 24-kDa soluble heme degradation enzyme in Corynebacterium diphtheriae, is coordinated axially to a neutral imidazole of a proximal histidine residue in HmuO. EPR of the NO-bound ferrous heme-HmuO mutant complexes reveals His20 as the proximal heme ligand in HmuO, and this is confirmed by resonance Raman result from the ligand free ferrous heme-H20A. When bound with exogenous imidazole, His20A mutant resumes full catalytic activity. Hence, it is the absence of the proximal His ligand, that is responsible for the inactivity of proximal His mutant.
(2)We found that the mutation of R183 to E or D of rat HO-1 changes the a-regioselectivity of the HO catalysis. The result shows the importance of the hydrogen bonding interaction between the arginine at position 183 and the carboxylates of the heme propionate group, as well as steric effect of the distal helix, for the a-regioselectivity.
(3)Wild-type enzyme of rat HO-1 degrades heme to verdoheme with hydrogen peroxide. However, D140A heme complex forms compound II with hydrogen oeroxide, and no heme degradation occurs. D140E mutant degrades heme normally, but D140N shows reactivity similar to that of D140A. These results indicate that the carboxylate at position 140 is essential to activate the iron-bound oxygen.
(4)We determined the crystal structure of rat biliverdine reductase. The structure contains two domains: an N-terminal domain characteristic of a nucleotide binding fold and a C-terminal domain. We proposed modes of binding for NADPH and biliverdin.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Yoshida Tadashi: "Mechanism of heme degradation by heme oxygenase"Journal of Inorganic Biochemistry. 82. 33-41 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Grace C.Chu: "Histicline 20, The crucial protimal oxial heme ligand of bacterial heme oxygenase Hum O from Corynebacterium"Journal of Biological Chemistry. 275. 17494-17500 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sun Danyu: "Crystallization and preliminary X-ray diffraction analysis of rat biliverdin redactase"Acta Crystallography. D56. 1180-1182 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Zhou Hong: "Participation of carboxylate amino acid chain in regisspecific oxidation of heme by heme oxygenase"Journal of America Chemical Society. 122. 8311-8312 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akira Kikuchi: "Crystal structure of rat biliverdin reductase"Nature Structural Biology. 8. 221-225 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujii Hiroshi: "A role for highly conserved carboxylate, aspartate-140, in oxygen activation and heme degradation by heme oxygenase-1"Journal of American Chemical Society. 123. 6475-6484 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Zhou, Hong et al.: "Basic amino acid residues of heme oxygenase for electron transfer between NADPH-cytochrom P-450 reductase and heme oxygenase as revealed by alanine-scanning mutagaenesis."Yamagata Med. J.. 18. 25-36 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Chu Grace C. et al.: "Histidine 20, the crutial proximal axial heme ligand of bacterial heme oxygenase Hmu 0 form Corynebacterium diphtheriae."J. Biol. Chem.. 275. 174949-17500 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sun, Danyu et al.: "Crystallization and preliminary X-ray diffraction analysis of rat biliverdin reductase."Acta Cryst.. D56. 1180-11820 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Zhou, Hong et al.: "Participation of carboxylate amino acid side chain in regiospecific oxidation of heme by heme oxygenase"J. Am. Chem. Soc.. 122. 8311-8312 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Chu GraceC. et al.: "Axial ligation states of five-coordinatgeheme oxygenase histidine mutants, as revealedby EPR and resonance Raman spectroscopy."J. Am. Chem. Soc.. 122. 12612-12613 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kikuchi Akihiro et al.: "Crystal structure of rat biliverdin reductase"Nat. Struct. Biol.. 8. 221-225 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujii, Hiroshi et al.: "A role of highly conserved carboxylate, asparatate-140 in oxygen activation and heme degradation by heme oxygenase-1"J. Am. Chem. Soc.. 123. 6475-6484 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Roman Davydov: "Catalytic mechanism of heme oxygenase throuth EPR and ENDOR of cryoreduced oxy-heme oxygenase and its Asp140 mutants"Journal of American Chemical Society. 124・8. 1798-1808 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujii Hiroshi: "A role for highly conserved carboxylate,aspartate-140,in oxyen activation and heme degradation by heme oxygenase-1"Journal of American Chemical Society. 123・27. 6475-6484 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Akihiro Kikuchi: "Crystal structure of rat biliverdin reductase"Nature Structural Biology. 8(3). 221-225 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Grace C.Chu: "Axial ligation state of five-coordinate Rene oxygenase proximal histidine mutant, as revealed by EPR"Journal of American Chemical Society. 122(50). 12612-12613 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Zhou Hong: "Participation of cartoxglate amins acid side chair in regiospecific oxidation of home by home oxygenase"Journal of American Chemical Society. 122(34). 8311-8312 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sun Danyu: "Crystallization and preliminary X-ray diffraction analysis of a rat biliverdin reductase"Acta Crystallography. D56. 1180-1182 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Grace C.Chu: "Histidine 20, the crucial proximal axial home ligand of bacterial home oxygenase Hum O from Corynebacterium"Journal of Biological Chemietry. 275(23). 17494-17500 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoshida Tadashi: "Mechanism of home degradation by home oxygenase"Journal of Inorganic Biochemistry. 82. 33-41 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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