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Product release mechanism of Lipocalin-type Prostaglandin D synthase

Research Project

Project/Area Number 24790055
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Physical pharmacy
Research InstitutionKinki University

Principal Investigator

SHIMAMOTO Shigeru  近畿大学, 理工学部, 助教 (00610487)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywordsリポカリン型プロスタグランジンD合成酵素 / プロスタグランジンD2 / NMR / ITC / プロスタグランジンD
Research Abstract

Lipocalin-type Prostaglandin D synthase (L-PGDS) catalyzes the isomerization of prostaglandin H2 (PGH2) to produce prostaglandin D2 (PGD2), which acts as a potent endogenous somnogen in the brain. A number of studies of L-PGDS, as a drug target for sleep disorders, have been reported in attempts to understand its catalytic mechanism, and several substrate recognition models of L-PGDS have been proposed. However, details of the mechanism by which L-PDGS recognizes its substrates and products are obscure, since essential information, such as its binding affinity and stoichiometry, of the interactions between L-PGDS and its substrates and products remains unclear. Therefore, we carried out ITC and NMR experiments to characterize the binding properties. The results of the ITC and NMR measurements revealed that both the substrate and the product bind to L-PGDS in a stoichiometry of 2 to 1 and two binding sites, namely a high and a low affinity binding site, are present.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (17 results)

All 2014 2013 2012

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (8 results)

  • [Journal Article] Chemical methods and approaches to the regioselective formation of multiple disulfide bonds2014

    • Author(s)
      Shimamoto S., Katayama H., Okumura M., and Hidaka Y
    • Journal Title

      Curr. Protoc. Protein Sci

      Volume: 76

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chemical Assistance of Disulfide Coupled Peptide and Protein Folding2014

    • Author(s)
      Okumura M., Shimamoto S., and Hidaka Y
    • Journal Title

      Curr. Protoc. Protein Sci

      Volume: 76

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] ^1H, ^<13>C, and ^<15>N resonance assignments of mouse lipocalin-type prostaglandin D synthase/substrate analog complex2014

    • Author(s)
      Shimamoto S., Maruo H., Yoshida T., and Ohkubo T
    • Journal Title

      Biomol. NMR Assign

      Volume: 8(1) Pages: 129-132

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] (1)H, (13)C, and (15)N resonance assignments of mouse lipocalin-type prostaglandin D synthase/substrate analog complex.2014

    • Author(s)
      Shimamoto Shigeru, Maruo Hiroko, Yoshida Takuya, Ohkubo Tadayasu.
    • Journal Title

      Biomolecular NMR Assignments

      Volume: 8 Issue: 1 Pages: 129-132

    • DOI

      10.1007/s12104-013-9467-5

    • Related Report
      2013 Annual Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Folding of Peptides and Proteins : Role of Disulfide Bonds, Recent Developments2013

    • Author(s)
      Hidaka Y., and Shimamoto S
    • Journal Title

      Biomol. Concepts

      Volume: 4(6) Pages: 597-604

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Folding of Peptides and Proteins: Role of Disulfide Bonds, Recent Developments2013

    • Author(s)
      Hidaka Yuji, Shimamoto Shigeru.
    • Journal Title

      BioMolecular Concepts

      Volume: 4 Pages: 597-604

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of positively charged redox molecules on disulfide-coupled protein folding2012

    • Author(s)
      Okumura M., Shimamoto S., Nakanishi T., Yoshida Y., Konogami T., Maeda S., and Hidaka Y
    • Journal Title

      FEBS Lett

      Volume: 586(21) Pages: 3926-3930

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A chemical method for investigating disulfide-coupled peptide and protein folding2012

    • Author(s)
      Okumura M., Shimamoto S., and Hidaka Y
    • Journal Title

      FEBS J

      Volume: 279(13) Pages: 2283-2295

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Drug delivery system for poorly water-soluble compounds using lipocalin-type prostaglandin D synthase2012

    • Author(s)
      Fukuhara A., Nakajima H., Miyamoto Y., Inoue K., Kume S., Lee Y.H., Noda M., Uchiyama S., Shimamoto S., Nishimura S., Ohkubo T., Goto Y., Takeuchi T., and Inui T
    • Journal Title

      J. Control. Release

      Volume: 159(1) Pages: 143-150

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] STRUCTURAL AND DYNAMIC ANALYSIS OF LIPOCALIN TYPE PROSTAGLANDIN D SYNTHASE IN ITS APO FORM AND SUBSTRATE ANALOG COMPLEX FORM2014

    • Author(s)
      Shimamoto S., Ohkubo T., Aritake K., Urade Y., and Hidaka Y
    • Organizer
      Biophysical Society 58th Annual Meeting (2014)
    • Place of Presentation
      San Francisco, California(262-Pos)
    • Related Report
      2013 Final Research Report
  • [Presentation] ANALYSES OF THE INTERACTION BETWEEN LIPOCALIN-TYPE PROSTAGLANDIN D SYNTHASE AND SUBSTRATE OR PRODUCT2014

    • Author(s)
      Fukuda Y., Maruno T., Kobayashi Y., Ohkubo T., Aritake K., Urade Y., Hidaka Y., and Shimamoto S
    • Organizer
      Society 58th Annual Meeting (2014)
    • Place of Presentation
      San Francisco, California(3422-Pos)
    • Related Report
      2013 Final Research Report
  • [Presentation] Analyses of the Interaction between Lipocalin-type Prostaglandin D Synthase and Substrate or Product2014

    • Author(s)
      Yutaro Fukuda, Takahiro Maruno, Yuji Kobayashi, Tadayasu Ohkubo, Kosuke Aritake, Yoshihiro Urade, Yuji Hidaka, Shigeru Shimamoto
    • Organizer
      58th Annual Meeting of the Biophysical Society
    • Place of Presentation
      San Francisco (USA)
    • Related Report
      2013 Annual Research Report
  • [Presentation] STRUCTURAL AND DYNAMIC ANALYSIS OF LIPOCALIN TYPE PROSTAGLANDIN D SYNTHASE IN ITS APO FORM AND SUBSTRATE ANALOG COMPLEX FORM.2014

    • Author(s)
      Shigeru Shimamoto, Tadayasu Ohkubo, Kosuke Aritake, Yoshihiro Urade, Yuji Hidaka
    • Organizer
      58th Annual Meeting of the Biophysical Society
    • Place of Presentation
      San Francisco (USA)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Analyses of the Interaction between Lipocalin-type Prostaglandin D Synthase and Substrate or Product2013

    • Author(s)
      Fukuda Y., Maruno T., Kobayashi Y., Ohkubo T., Aritake K., Urade Y., Hidaka Y., and Shimamoto S
    • Organizer
      4th Asia-Pacific International Peptide Symposium (2013)
    • Place of Presentation
      大阪(P-054)
    • Related Report
      2013 Final Research Report
  • [Presentation] リポカリン型プロスタグランジンD合成酵素と基質・生成物の相互作用解析2013

    • Author(s)
      福田裕太郎、島本茂、丸野孝浩、小林祐次、大久保忠恭、有竹浩介、裏出良博、日高雄二
    • Organizer
      第13回日本蛋白質科学会(2013)
    • Place of Presentation
      鳥取(1P-079)
    • Related Report
      2013 Final Research Report
  • [Presentation] リポカリン型プロスタグランジンD合成酵素と基質・生成物の相互作用解析2013

    • Author(s)
      福田裕太郎、島本茂、丸野孝浩、小林祐次、大久保忠保、有竹浩介、裏出良博、日高雄二
    • Organizer
      第13回 日本蛋白質科学会
    • Place of Presentation
      とりぎん文化会館(鳥取県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Analyses of the Interaction between Lipocalin-type Prostaglandin D Synthase and Substrate or Product2013

    • Author(s)
      Yutaro Fukuda, Takahiro Maruno, Yuji Kobayashi, Tadayasu Ohkubo, Kosuke Aritake, Yoshihiro Urade, Yuji Hidaka, Shigeru Shimamoto
    • Organizer
      4th asia-pacific international peptide symposium
    • Place of Presentation
      ホテル阪急エキスポ(大阪府)
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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