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Revealing structural basis for development of a novel drug against multidrug-resistant HIV

Research Project

Project/Area Number 24790049
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Physical pharmacy
Research InstitutionIwaki Meisei University

Principal Investigator

suzuki kaoru  いわき明星大学, 薬学部, 客員研究員 (90382788)

Project Period (FY) 2012-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsHIV感染 / 抗HIV薬 / タンパク質 / 糖鎖 / レクチン / X線結晶構造解析 / 感染症 / 薬学 / HIV感染 / HIV感染予防 / HIV感染予防 / X線 / 構造解析 / 構造薬学
Outline of Final Research Achievements

HIV/AIDS is a major health concern, it is a global pandemic which remains relatively uncontrolled infectious disease. We independently succeeded in discovering a new lectin, actinohivin (hereafter designate AH), from actinomycete. AH is an excellent candidate for development as an antiretrovial drug to treat or prevent HIV infection.
In order to obtain structural insights into the anti-HIV activity of AH, we crystallized AH and in complex with the target α(1-2)mannobiose (Man2) and α(1-2)(1-2)mannotriose (Man3) moiety of the high-mannose-type glycan (HMTG) attached to HIV-1 gp120. Its crystal structure was successfully solved, revealing that AH is composed of three repeated modules that are closely associated with each other.The present study confirmed that the three mannobiose-binding pockets of AH are almost the same or equivalent and that their tertiary structures are rather rigid.

Report

(6 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (7 results)

All 2014 2013 2012

All Journal Article (4 results) (of which Peer Reviewed: 3 results) Presentation (3 results)

  • [Journal Article] Structural analyses of actinohivin with glucan for development of HIV preventer2014

    • Author(s)
      Masaru Tsunoda, Kaoru Suzuki, Yoichi Takeda and Yukishige Ito
    • Journal Title

      Photon Factory Activity Report 2013

      Volume: 31 Pages: 395-395

    • Related Report
      2014 Research-status Report
  • [Journal Article] Peculiarity in crystal packing of anti-HIV lectin actinohivin in complex with α(1-2)mannobiose2013

    • Author(s)
      Kaoru Suzuki, Masaru Tsunoda, M. Mominul Hoque, Fang Zhang, Jiandong Jiang, Xiaoxue Zhang, Naomi Ohbayashi, Haruo Tanaka & Akio Takénaka
    • Journal Title

      Acta Crystallogr. Sect. D

      Volume: D69 Issue: 9 Pages: 1818-1825

    • DOI

      10.1107/s0907444913017812

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Crystallographic study of the interaction of the anti-HIV lectin actinohivin with the alpha(1-2)mannobiose moiety of gp120 HMTG2012

    • Author(s)
      Kaoru Suzuki, Naomi Ohbayashi, Jiandong Jiang, Xiaoxue Zhang, M. Mominul Hoque, Masaru Tsunoda, Kazutaka Murayama, Haruo Tanaka and Akio Takenaka
    • Journal Title

      Acta Crystallogr. Sect. F

      Volume: 68 Issue: 9 Pages: 1060-1063

    • DOI

      10.1107/s1744309112031077

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Structural insights into the specific anti-HIV property of actinohivin; Crystal structure of its complex with the alpha(1-2)mannobiose moiety of gp1202012

    • Author(s)
      M. Mominul Hoque, Kaoru Suzuki, Masaru Tsunoda, Jiandong Jiang, Fang Zhang, Atsushi Takahashi, Naomi Ohbayashi, Xiaoxue Zhang, Haruo Tanaka, Satoshi Omura and Akio Takenaka
    • Journal Title

      Acta Crystallogr. Sect. D

      Volume: 68 Issue: 12 Pages: 1671-1679

    • DOI

      10.1107/s0907444912040498

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] アクチノヒビンが示す標的α(1-2)マンノビオースとの複合体の結晶構造における奇妙な性質2013

    • Author(s)
      角田大、鈴木薫
    • Organizer
      日本結晶学会
    • Place of Presentation
      熊本大学
    • Related Report
      2013 Research-status Report
  • [Presentation] Structural insights of a potent anti-HIV actinohivin upon binding specifically to the target oligomannose of HMTG attached to HIV-gp1202012

    • Author(s)
      鈴木薫
    • Organizer
      日本結晶学会
    • Place of Presentation
      東北大学
    • Related Report
      2012 Research-status Report
  • [Presentation] Structural insights of a potent anti-HIV actinohivin upon binding specifically to the target oligomannose of HMTG attached to HIV-gp1202012

    • Author(s)
      角田大
    • Organizer
      AsCA 12/CRYSTAL 28 and Bragg Centennial Symposium
    • Place of Presentation
      Adelaide Convention Centre and Elder Hall, The University of Adelaide, Australia
    • Related Report
      2012 Research-status Report

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

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