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1994 Fiscal Year Final Research Report Summary

Elucidation of the steric bases of anticancer activities of interferons through a combined approach by X-ray crystal structure analyzes and protein engineering.

Research Project

Project/Area Number 04404088
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field 結晶学
Research InstitutionNagaoka University of Thchnology

Principal Investigator

MITSUI Yukio  Nagaoka University of Technology Faculty of Engineering, Professor, 工学部, 教授 (40012637)

Co-Investigator(Kenkyū-buntansha) KAWANO Genji  Toray Industries Inc., Institute for Biomedical Research, Pricipal Investigator, 医療システム研究所, 主席研究員
Project Period (FY) 1992 – 1994
KeywordsTwo-dimensional X-ray diffractometer / Protein crystallography / Cytokine / Interferon / X-ray crystal structure analysis / Protein engineering / Structure-activity relationship
Research Abstract

1) Set-up of the X-ray diffractometer system.
The "recording device for diffracted X-ray beam", whcih was purchased by the present grant, completed the set-up of the two-dimensional X-ray diffraactometer using Imaging Plates.
2) Set-up of the computer graphics system.
The "CPU-upgrading system" purchased by the present grant, was succesfully incorporated into the existing system extensively upgrading its performance.
3) Refinement of the crystal structure of murine interferon-beta
Using the systems 1) and 2) above, the structure has been refined at 2.15 A resolution to an R-factor of 19.1%. Extensive modification was found necessary for the A-Helix portion (EMBO Journal 4,3193-3201 (1993) ; also submitted to J.Mol.Biol.)
4) Prediction of the three-dimensional structures for various Type I interferons.
Structure prediction was done for the following four interferons : human-alphaD,human-beta, bovine & ovine tau's. A huge data set of the structure-activity relationship studiesdirected for Type I interferons were compiled and systematically evaluated based on the established three-dimensional structure(Pharmacology & Therapeutics, 58,93-132 (1993)).
5) Yet another challenege for the crystallization of human interferon-alpha.13EA10 : The attempt failed as before indicating that there must be some fundamental reason for non-crystallizability. More systematic approaches making use of a dynamic light scattering device (for example) would be necessary.

  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] T.Senda,T.Shimazu,S.Matsuda,Y.Mitsui: "Three-dimensional crystal structure of recombinant murine interferon-β" EMBO Journal. 11. 3193-3201 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Takeuchi,T.Nonaka,Y.Mitsui: "Crystal structure of an engineered subtilisin inhibitor complexed with bovine trypsin" Proc.Natl.Acad.Sci.(USA). 89. 4407-4411 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mitsui,Y. Senda,T.Shimazu,T.,Matsuda,S.and Utsumi J.: "Structural implications of the threedimensional structure of interferon-β." Pharmacology and Therapeutics. 58. 93-132 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nonaka,T.,Nakamura,K.T.,Uesugi.S.,Ikehara,M.,Irie,M.and Mitsui Y.: "Crystal structure of ribonuclease Ms complexed with a GpC analogue." Biochemistry. 32. 11825-11837 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 三井幸雄、千田俊哉、野中孝昌: "広がる放射光利用-蛋白質の構造解析-" 放射線と産業. 60. 25-29 (1993)

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      「研究成果報告書概要(和文)」より
  • [Publications] 野中孝昌、三井幸雄: "生体高分子のX線解析-最近の進歩-" 有機合成化学協会誌. 51. 551-562 (1993)

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      「研究成果報告書概要(和文)」より
  • [Publications] 千田俊哉、三井幸雄、野中孝昌: "迅速な蛋白質立体構造決定システム" 学術月報. 48. 203-203 (1994)

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      「研究成果報告書概要(和文)」より
  • [Publications] Irie,M.,Ohgi,K.,Watanabe,H.,Iwama,M.,Nakamura,K.T.Kurihara,H.,Nonaka,,T., Mitsui,Y.,Horiuchi,H.& Takagi,M.: "pH Profile of kinetic constants of RNase Rh and possible mechanism of the enzyme." J.Biochem.(Tokyo). 115. 1083-1087 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sugiyama,K.,Senda,T.,Narita,H.,Yamamoto,T.,Kimbara,K.,Fukuda,M.,Yano,K.& Mitsui,Y: "Three-dimensional structure of 2,3-dihydroxy-phenyl dioxygenase from Pseudomonas" Proc.Japan Acad.71B. 32-35 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sugiyama,K.Narita,H.,yamamoro,T.,Senda,T.,Kimbara,K.,Inokuchi,N.,Iwama,M.,Irie,M.,Fukuda,M.,Yano,K.& Mitsui,Y: "Crystallization of a 2,3-dihydroxybiphenyl dioxygenase from Pseudomonas" Proteins:Structure,Function and Evolution,. (in press.). (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Senda,T.Saitoh,S.& Mitsui,Y.: "Refined crystal structure of recombinant murine interferon at 2.15 A resolution." J.Mol.Biol.,. (in press.). (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 野中孝昌、三井幸雄: "リボヌクレアーゼの立体構造と反応機構" 蛋白質・核酸・酵素 増刊号「核酸化学の新展開」. (印刷中). (1995)

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      「研究成果報告書概要(和文)」より
  • [Publications] Kohno,T.,Senda,T.,Narumi,H.,Kimura,S.& Mitsui,Y.: "3D-structure of abrin-a A-chain having ribosome inactivating activity" Proc.Japan Acad.72B(in press.). (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Senda,T.,Nonaka,T.,Nakamura,K.T.& Mitsui,Y.: "“Synchrotron Radiation in Biosciences"" Clarendon Press, 8 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 野中孝昌、三井幸雄(共著): "蛋白質プロテアーゼ・インヒビターによるプロテアーゼの分子識別" 共立出版(三浦謹一郎 編), 7 (1993)

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      「研究成果報告書概要(和文)」より
  • [Publications] 三井幸雄(共著): "生命分子工学" 裳華房, 20 (1992)

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      「研究成果報告書概要(和文)」より
  • [Publications] Asano, K., Fujita, S., Senda, T., & Mitsui, Y.: "Crystal structure of rionuclease S under microgravity" J.Cryst. Growth. 182. 323-329 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeuchi, Y., Nonaka, T., Nakamura, K.T., Kojima, S., Miura, K.& Mitsui, Y.: "Crystal structure of an engineered subtilisin inhibitor complexed with bovine trypsin." Proc. Natl. Acad. Sci. (USA). 89. 4407-4411 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Senda, T., Shimizu, T., Matsuda, S., Kawano, G., Shimizu, H., Nakamura, K.T., & Mitsui, Y.: "Three-dimensional crystal structure of recombinant murine interferon-beta." EMBO J.11. 3193-3201 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kurihara, H., Mitsui, Y., Ohgi, K., Irie, M., Mizuno, H.& Nakamura, K.T.: "Crystal and molecular structure of RNase Rh, a new class of microbial ribonuclease from Rhizopus niveus." FEBS Letters. 306. 189-192 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nonaka, T., Nakamura, K.T., Uesugi, S., Ikehara, M., Irie, M.& Mitsui, Y.: "Crystal structure of ribonuclease Ms (as an ribonuclease T1 homologue) complexed with a guanylyl-3', 5'-cytidine analogue." Biochemistry. 32. 11825-11837 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mitsui, Y., Senda, T., Shimazu, T., Matsuda, S.& Utsumi, J.: "Structural, functional and evolutionary implications of the three-dimensional structure of murine interferon-beta." Pharmacology and Therapeutics. 58. 93-132 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Senda, T., Nonaka, T., Nakamura, K.T.& Mitsui, Y.: "Protein structure analyzes exploiting the data collection efficiency and precision provided by the macromolecule-oriented Weissenberg camera installed at Beam Line 6A2 of the Photon Factory, Tsukuba." In "Synchrotron Radiation in Biosciences" (Chance, B., Sakabe, N.et al.eds.) Clarendon Press.77-85 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Irie, M., Ohgi, K., Watanabe, H., Iwama, M., Nakamura, K.T., Kurihara, H., Nonaka, T., Mitsui, Y., Horiuchi, H.& Takagi, M.: "pH Profile of kinetic constants of RNase Rh from Rhizoppus niveus and its mutant enzymes towards UpU and possible mechanisms of RNase Rh. J.Biochem. (Tokyo)" 115. 1083-1087 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sugiyama, K., Senda, T., Narita, H., Yamamoto, T., Kimbara, K.Fukuda, M., Yano, K.& Mitsui, Y.: "Three-dimenaional structure of 2,3-dihdroxyphenyl dioxygenase from Pseudomonas sp.strain KKS102 having polychlorinated biphenyl (PCB)-degrading activity." Proc.Japan Acad.71B. 32-35 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kohno, T., Senda, T., Narumi, H., Kimmura, S.& Mitsui, Y.: "Three-dimensional structure of abrin-a A-chain having ribosome inactivating activity." Proc.Japan Acad.(in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sugiyama, K., Narita, H., Yamamoto, T., Senda, T., Kimbara, K., Inokuchi, N., Iwama, M., Irie, M., Fukuda, M., Yano, K.& Mitsui, Y.: "Crystallozation and preliminary crystallographic analysis of a 2,3-dihydroxybiphenyl dioxy-genase from Pseudomonas sp.strain KKA102 having polychlorinated biphenyl (PCB) degrading activity." Proteins : Structure, Function and Evolution. (in press.). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Senda, T., Saitoh, S.& Mitsui, Y.: "Refined crystal structure of recombinant murine interferon-beta at 2.15 A resolution and its relationship to those of the other Type I interferons." J.Mol.Biol.(in press.). (1995)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1996-04-15  

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