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

新型强效抗 HIV 凝集素与 HIV-gp120 寡甘露糖复合物的结构基础

• 批准号: 23570147
• 负责人: TAKENAKA Akio
• 金额: $ 3.49万
• 依托单位: Iwaki Meisei University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23570147/
• 关键词: Ｘ線結晶解析; 抗ＨＩＶレクチン; オリゴマンノース; 抗HIVレクチン; 糖鎖認識機構; アクチノヒビン; X線構造解析; タンパク質の立体構造; HMTG結合機構

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.

凝集素放线菌素（AH）有望成为一种阻止HIV-1进入人类易感细胞的候选新药。为了揭示AH与HIV-1表面突出的HMTG特异性相互作用的结构细节，用X射线晶体学方法测定了AH与主要靶点α（1-2）甘露二糖和α（1-2）甘露三糖复合物的晶体结构，结果表明主要靶点α（1-2）甘露三糖呈双括号状构象，为刚性结构，AH与之结合，以严格地以锁和钥匙的方式识别靶标，除了氢键之外还有如此多的疏水相互作用。这些结构特征有助于开发AH作为更有效的抗逆转录病毒药物，以抑制HIV/AIDS的传染性扩展，并有助于在不久的将来加速结束HIV/AIDS的流行。

项目成果

The characteristic structure of anti-HIV actionhivin in complex with three HMTG-D1 chains of HIV-gp120

抗HIV Actionhivin与HIV-gp120的三个HMTG-D1链复合物的特征结构

• 发表时间: 2014
• 期刊: Acta Crystallogr. Sect. F.
• 作者: Fang Zhang;Mominul M. Hoq;Jiandong Jiang;Kaoru Suzuki;Masaru Tsunoda;Yoichi Takeda;Yukishige Ito;Haruo Tanaka and Akio Takenaka.
• 通讯作者: Haruo Tanaka and Akio Takenaka.

Structure insight of anti-HIV actinohivin in complex with a(1,2)mannotriose

抗 HIV 放线菌素与 (1,2) 甘露三糖复合物的结构洞察

• 发表时间: 2013
• 作者: F. Zhang;M.M. Hoque;K. Suzuki;M. Tsunoda;Y. Takeda;Y. Ito;H. Tanaka and Akio Takenak.
• 通讯作者: H. Tanaka and Akio Takenak.

The characteristic structure of anti-HIV actinohivin in complex with three HMTG-D1 chains of HIV-gp120

抗HIV放线菌素与HIV-gp120的三个HMTG-D1链复合物的特征结构

• 发表时间: 2014
• 期刊: Acta Crystallogr. Sect. D
• 作者: Fang Zhang;Mominul M. Hoq;Jiandong Jiang;Kaoru Suzuki;Masaru Tsunoda;Yoichi Takeda;Yukishige Ito;Haruo Tanaka and Akio Takénaka
• 通讯作者: Haruo Tanaka and Akio Takénaka

Structural insight of anti-HIV lectin actinohivin specifically bound to HMTG of gp120

与 gp120 的 HMTG 特异性结合的抗 HIV 凝集素放线菌素的结构见解

• 发表时间: 2013
• 作者: M. Tsunoda;M.M. Hoque;J. Jiang;K. Suzuki;Ohbayashi;X. Zhang;T. Sekiguchi;H. Tanaka and Akio Takenaka.;Akio Takenaka.
• 通讯作者: Akio Takenaka.

Specificity and efficiency in activity of anti-HIV actinohivin for sugar binding

抗 HIV 放线菌素糖结合活性的特异性和效率

• 发表时间: 2011
• 作者: M.M. Hoque;J. Jiang;K. Suzuki;M. Tsunoda;A. Takahashi;T. Sekiguchi;H. Tanaka and Akio Takenaka
• 通讯作者: H. Tanaka and Akio Takenaka