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The activating mechanism of the FGFR3 pathogenic mutants

Research Project

Project/Area Number 24590056
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Physical pharmacy
Research InstitutionOsaka Prefecture University

Principal Investigator

KINOSHITA Takayoshi  大阪府立大学, 理学(系)研究科(研究院), 准教授 (90405340)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords受容体型キナーゼ / 病原活性変異体 / X線結晶構造解析 / 酵素機能解析 / FGFR3 / 受容体型チロシンキナーゼ / 活性化機構 / がん / シグナル伝達 / X線結晶構造解析 / 活性変異体
Outline of Final Research Achievements

In order to facilitate drug discovery for cancer, we aim to elucidate the activating mechanism of the FGFR3 pathogenic mutants by the functional and crystallographic analyses. The Km (ATP) values of N540T, K650M, and G697C mutants varied from 0.30- to 108-hold compared with that of the wild type. The result implies that these mutants are activated via distinguished mechanisms. The exploration of crystallization condition has yielded the micro-crystals of the wild type and mutants. Ongoingly, we will perform the crystal analyses and elucidate the molecular mechanisms for the activation of the active mutants.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (4 results)

All 2015 2014 2013 2012

All Presentation (4 results)

  • [Presentation] 病原性FGFR3活性変異体の構造機能解析2015

    • Author(s)
      露口正人、力津朗、藤井翔太、木下誉富
    • Organizer
      バイオメディカルフォーラム2015
    • Place of Presentation
      大阪府立大学
    • Year and Date
      2015-01-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] 恒常活性を示すFGFR3病原活性変異体の構造機能研究2014

    • Author(s)
      露口正人、力津朗、藤井翔太、曽我部祐里、桐井康行、木下誉富
    • Organizer
      平成26年度日本結晶学会年会
    • Place of Presentation
      東京大学
    • Year and Date
      2014-11-01 – 2014-11-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] FGFR3病原活性変異体の構造機能研究2013

    • Author(s)
      露口正人、力津朗、藤井翔太、曽我部祐里、合田正貴、桐井康行、木下誉富
    • Organizer
      第13回日本蛋白質科学会年会
    • Place of Presentation
      鳥取
    • Related Report
      2013 Research-status Report
  • [Presentation] 受容体チロシンキナーゼFGFR3のX線結晶構造解析2012

    • Author(s)
      藤井翔太、力津朗、桐井康行、合田正貴、多田俊治、木下誉富
    • Organizer
      平成24年度日本結晶学会年会
    • Place of Presentation
      東北大学
    • Related Report
      2012 Research-status Report

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

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