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.
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.
1 Zhu, G.-Y.; Li, Y.-W.; Hua, D.-K.; Jiang, Z.-H.; Yu, Z.-L.; Fong, W.-F. J. Agric. Food Chem. 2011, 59(1), 200.
2 Li, J.; Xie, Z.-Z.; Tang, Y.-B.; Zhou, J.-G.; Guan, Y.-Y. Eur. J. Pharmacol. 2011, 652, 104.
3 Han, J.-Y.; In, J. G.; Kwon, Y. S.; Choi, Y. E. Phytochemistry2010 , 71(1), 36.
4 Tetsuo, K.; Masaaki, S.; Yutaka, E. Eur. J. Biochem. 1998,256, 238.
5 Zhao, X.; Wang, S.; Xu, X.-H.; Huang, X.-R. Acta Chim. Sinica 2009, 67, 1835 (in Chinese). (赵熹, 王嵩, 徐晓华, 黄旭日, 化学学报, 2009, 67,1835.)
6 Wang, S.; Huang, X.-R.; Gao, X.-F.; Zhao, X.; Sun, C.-C. Chem. J. Chin. Univ. 2006, 27(3), 535 (in Chinese). (王嵩, 黄旭日, 高雪峰, 赵熹, 孙家钟, 高等学校化 学学报, 2006, 27(3), 535.)
7 Kiefer, F.; Arnold, K.; Künzli, M.; Bordoli, L.; Schwede, T.Nucleic Acids Res. 2009, 37, 387.
8 Arnold, K.; Bordoli, L.; Kopp, J.; Schwede, T. Bioinformatics 2006, 22, 195.
9 Trott, O.; Olson, A. J. J. Comput. Chem. 2010, 31, 455.
10 Huey, H.; Morris, G. M.; Olson, A. J. J. Comput. Chem.2007, 28, 1145.
11 Han, W.-W.; Zhou, Y.-H.; Yao, Y.; Li, Z.-S. Polymer 2006,47, 7953.
12 Han, W.-W.; Li, Z.-S.; Zheng, Q.-C.; Sun, C.-C. J. Theor. Comput. Chem. 2006, 5, 433.
13 Affinity User Guide, Accelrys Inc, San Diego, USA, 1999.
14 Han, W.-W.; Zhou, Y.-H.; Yao, Y.; Li, Z.-S. J. Mol. Struct.2007, 815, 87.
15 Thoma, R.; Schulz-Gasch, T.; D-Arcy, B.; Benz, J.; Aebi, J.; Dehmlow, H.; Hennig, M.; Stihle, M.; Ruf, A. Nature 2004, 432, 118.
16 Benkert, P.; Künzli, M.; Schwede, T. Nucleic Acids Res. 2009, 37, 510.
