化学学报 ›› 2012, Vol. 70 ›› Issue (03): 217-222.DOI: 10.6023/A1108313    下一篇

研究论文

人参β-香树素合成酶同源模建及高通量虚拟筛选抑制剂的研究

詹冬玲a, 王嵩b, 韩葳葳c, 刘景圣a   

  1. a 吉林农业大学食品科学与工程学院 长春 130118;
    b 吉林大学理论化学研究所理论化学计算国家重点实验室 长春 130061;
    c 吉林大学分子酶学工程教育部重点实验室 长春130023
  • 收稿日期:2011-08-31 修回日期:2011-11-10 出版日期:2012-02-14 发布日期:2011-11-23
  • 通讯作者: 刘景圣 E-mail:liujs1007@vip.sina.com.cn
  • 基金资助:

    国家自然科学基金(No. 31070638)、吉林省自然科学基金(Nos. 20101552, 201015109)和教育部博士点专项基金(No. 20090061120101)资助项目.

Study of Homology Modeling and High-throughout Screening of a New Inhibitor of Panax β-AS

Zhan Donglinga, Wang Songb, Han Weiweic, Liu Jingshenga   

  1. a College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118;
    b State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun 130061;
    c Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, Changchun 130023
  • Received:2011-08-31 Revised:2011-11-10 Online:2012-02-14 Published:2011-11-23
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 31070638), Natural Science Foundation of Jilin province (Nos. 20101552, 201015109) and Doctoral Fund of Ministry of Education (No. 20090061120101).

人参β-香树素合成酶(β-AS)能催化氧鲨烯环化生成齐墩果烷型皂苷, 从而减少植物固醇的生成量, 有助于获得高效的人参皂苷. 因β-AS 的三维结构是未知的, 我们以氧鲨烯环化酶为模板, 对β-AS 进行三维结构搭建. 以抑制剂10-aza-10,11-dihydro-2,3-oxidosqualene 为先导化合物, 通过AutoDockvina 进行分子对接, 选取结合能量最低的新化合物进行研究. 研究结果表明: 新抑制剂8442257 比先导化合物10-aza-10,11-dihydro-2,3-oxidosqualene 的抑制效果更好.Leu287 与新抑制剂结合时能量最低, 是重要的残基位点; Ser413 和Trp613 通过氢键与新抑制剂结合, 在抑制过程中起重要作用. 我们的研究结果为人参β-香树素合成酶抑制剂的研究提供一个有利的依据.

关键词: 同源模建, β-香树素合成酶, 虚拟筛选, 分子对接

β-Amyrin synthase from P ginseng (β-AS) catalyzes the biosynthesis of the cyclization of oxidosqualene into Oleanane-type saponins, thereby reducing the amount of steroid formation. However, the 3D structure of β-AS has not been firmly established. To finding the novel inhibitors, a 3D structure model of β-AS protein was constructed based on the structure of the template human oxidosqualene cyclase. After virtual screening technique of β-AS, a novel natural compound (8442257) has been found with the lowest affinity energy. Then we identify that Leu287 is the most important anchoring residues for binding with 8442257 because it has strong vdW interaction with inhibitor. Ser413 and Trp613 are important residues because they make hydrogen bonds with inhibitor. Our results may be helpful for further experimental investigations.

Key words: homology modeling, β-amyrin synthase, virtual screening, molecular docking