Structural basis on a new potent anti-HIV lectin in complex with oligomannoses of HIV-gp120

2013 Fiscal Year Final Research Report

• Project/Area Number: 23570147
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Iwaki Meisei University
• Principal Investigator: TAKENAKA Akio いわき明星大学, 薬学部, 研究員 (80016146)
• Project Period (FY): 2011 – 2013
• Keywords: Ｘ線結晶解析 / 抗ＨＩＶレクチン / オリゴマンノース

Research Abstract

Lectin actinohivin (AH) is expected as a new drug candidate that blocks entry of HIV-1 into human susceptible cells. In order to reveal the structural details of AH in the specific interaction with HMTG protruded from HIV-1 surface, several crystal structures of AH in complex with the targets alpha(1-2)mannobiose and alpha(1-2)mannotriose have been determined by X-ray crystallography.
These structures show that alpha(1-2)mannotriose of the principal target adopts a double bracket-shape conformation as a rigid structure, to which AH binds to recognize the target strictly in a Lock-and-Key fashion with so many hydrophobic interactions in addition to the hydrogen bonds. These structural features are useful for developing AH as a more effective antiretroviral drug to suppress the infectious expansion of HIV/AIDS and help expedite an end to the HIV/AIDS pandemic in the near future.

Research Products

• [Journal Article] The characteristic structure of anti-HIV actionhivin in complex with three HMTG-D1 chains of HIV-gp120 (2014)
  • Author(s): Fang Zhang, Mominul M. Hoq, Jiandong Jiang, Kaoru Suzuki, Masaru Tsunoda, Yoichi Takeda, Yukishige Ito, Haruo Tanaka and Akio Takenaka.
  • Journal Title: Acta Crystallogr. Sect. F. Volume: 70 Pages: (submitted)
  • Peer Reviewed
• [Journal Article] Peculiarity in crystal packing of anti-HIV lectin actinohivin in complex with a(1-2)mannobiose (2013)
  • Author(s): Kaoru Suzuki, Masaru Tsunoda, M. Mominul Hoque, Fang Zhang, Jiandong Jiang, Xiaoxue Zhang, Naomi Ohbayashi, Haruo Tanaka and Akio Takenaka.
  • Journal Title: Acta Crystallogr. Sect. D.
  • DOI: 10.1107/S0907444913017812
  • Peer Reviewed
• [Journal Article] Structural insights into the specific anti-HIV property of actinohivin; Crystal structure of its complex with the a(1-2)mannobiose moiety of gp120 (2012)
  • 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 Takénaka.
  • Journal Title: Acta Crystallogr. Sect. D. Volume: 68 Pages: 1671–1679
  • DOI: 10.1107/S0907444912040498
  • Peer Reviewed
• [Journal Article] Crystallographic study of the interaction of the anti-HIV lectin actinohivin with the a(1-2)mannobiose moiety of gp120 HMTG (2012)
  • 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 Pages: 1060–1063
  • DOI: 10.1107/S1744309112031077
  • Peer Reviewed
• [Presentation] アクチノヒビンが示す標的a(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): M. Tsunoda, M.M. Hoque, J. Jiang, K. Suzuki, Ohbayashi, X. Zhang, T. Sekiguchi, H. Tanaka and Akio Takenaka.
  • Organizer: 平成25年度日本結晶学会年会CrSJ-2013
  • Place of Presentation: 熊本, 日本
  • Year and Date: 20131011-13
• [Presentation] Structural insight of anti-HIV lectin actinohivin specifically bound to HMTG of gp120 (2013)
  • Author(s): Akio Takenaka.
  • Organizer: 瀋陽薬科大学セミナー
  • Place of Presentation: 瀋陽, 中国
  • Year and Date: 20130506-11
• [Presentation] The peculiar property in crystal packing of anti-HIV-1 lectin actinohivin (AH) complexed with the target a(1-2)mannobiose (MB) (2013)
  • Author(s): Akio Takenaka.
  • Organizer: IGBMC-CNRSセミナー
  • Place of Presentation: Strasbourg, France
  • Year and Date: 2013-09-02
• [Presentation] Structure insight of anti-HIV actinohivin in complex with a(1,2)mannotriose (2013)
  • Author(s): F. Zhang, M.M. Hoque, K. Suzuki, M. Tsunoda, Y. Takeda, Y. Ito, H. Tanaka and Akio Takenak.
  • Organizer: ヨーロッパ結晶学国際会議ECM28
  • Place of Presentation: Warwick, United Kingdom
  • Year and Date: 2013-08-25
• [Presentation] Structural insights of a potent anti-HIV actinohivin upon binding specifically to the target oligomannose of HMTG attached to HIV-gp120 (2012)
  • Author(s): M.M. Hoque, K. Suzuki, M. Tsunoda, J. Jiang, F. Zhang, A. Takahashi, N. Ohbayashi, X. Zhang, H. Tanaka and Akio Takenaka.
  • Organizer: アジア結晶学国際会議AsCA12
  • Place of Presentation: Adelaide, Australia
  • Year and Date: 20121202-06
• [Presentation] Structural insights of a potent anti-HIV actinohivin upon binding specifically to the target oligomannose of HMTG attached to HIV-gp120 (2012)
  • Author(s): M.M. Hoque, K. Suzuki, M. Tsunoda, J. Jiang, F. Zhang, A. Takahashi, N. Ohbayashi, X. Zhang, H. Tanaka and A. Takenaka.
  • Organizer: 日本結晶学会年会CrSJ2012
  • Place of Presentation: 仙台, 日本
  • Year and Date: 20121025-26
• [Presentation] Structural evidence of anti-HIV lectin actinohivin specific to HMTG of gp120 (2012)
  • Author(s): M.M. Hoque, J. Jiang, K. Suzuki, M. Tsunoda, N. Ohbayashi, X. Zhang, T. Sekiguchi, H. Tanaka and Akio Takenaka.
  • Organizer: ヨーロッパ結晶学国際会議ECM27
  • Place of Presentation: Bergen, Norway
  • Year and Date: 20120806-11
• [Presentation] Specificity and efficiency in activity of anti-HIV actinohivin for sugar binding (2011)
  • Author(s): M.M. Hoque, J. Jiang, K. Suzuki, M. Tsunoda, A. Takahashi, T. Sekiguchi, H. Tanaka and Akio Takenaka
  • Organizer: 国際結晶学連合大会IUCr-2011
  • Place of Presentation: Madrid, Spain
  • Year and Date: 20110822-30
• [Presentation] Structure determination (2) of anti-HIV actinohivin in complex with mannobioses (2011)
  • Author(s): J. Jiang, M.M. Hoque, K. Suzuki, M. Tsunoda A. Takahashi, T. Sekiguchi, H. Tanaka and Akio Takenaka.
  • Organizer: 国際結晶学連合大会IUCr-2011
  • Place of Presentation: Madrid, Spain
  • Year and Date: 20110822-30
• [Book] X線・中性子の散乱理論入門(和訳) (2014)
  • Author(s): 竹中章邛・藤井保彦
  • Total Pages: 211
  • Publisher: 森北出版
• [Remarks] 福島民報,平成24年12月21日(金), "抗HIVタンパク質アクチノヒビン,C型肝炎にも効果,いわき明星大研究チーム発見"
• [Remarks] 福島民友,平成24年12月21日(金), "C型肝炎治療へ一歩,HIV研究で解明,タンパク質に抑制機能"
• [Remarks] いわき民報,平成24年12月21日(金), "明星大学の研究グループ,C型肝炎への効果も発見アクチノヒビン"
• [Remarks]
  • URL: http://www.xtal.jp/BioSC/reports/index.html