草菇UBEV2蛋白同源模建筛选其小分子抑制剂  

Homology Modeling of Volvariella volvacea UBEV2 for Screening Its Small Molecule Inhibitory Compounds

作　　者：万佳宁[1] 尚俊军 汪滢[1] 李正鹏[1] 王莹[1] 唐利华[1] 茅文俊[1] 汪虹[1] 鲍大鹏[1] 龚明[1] WAN Jianing;SHANG Junjun;WANG Ying;LI Zhengpeng;WANG Ying;TANG Lihua;MAO Wenjun;WANG Hong;BAO Dapeng;GONG Ming(Institute of Edible Fungi,Shanghai Academy of Agricultural Sciences,Key Laboratory of Edible Fungi Resourcesand Utilization(South),Ministryof Agricultureand Rural Affairs,P R China,National Engineering Research Center of Edible Fungi,National R&D Center for Edible Fungi Processing,Shanghai 201403,China)

机构地区：[1]上海市农业科学院食用菌研究所,农业农村部南方食用菌资源利用重点实验室,国家食用菌工程技术研究中心,国家食用菌加工技术研发分中心,上海201403

出　　处：《食用菌学报》2020年第4期35-42,共8页Acta Edulis Fungi

基　　金：国家自然科学基金项目(32072642);上海市自然科学基金(18ZR1416800);上海市科技兴农项目(2018-02-08-00-12-F01555)。

摘　　要：草菇(Volvariella volvacea)具有典型的低温自溶特征,基于草菇低温自溶与一个泛素结合酶E2(ubiquitin-conjugating enzyme,UBE2)高表达及活性相关,采用虚拟筛选法获得潜在的草菇UBEV2抑制剂小分子化合物。结果表明:在2轮虚拟筛选方法得到500个靶中化合物的基础上,综合考虑可与UBEV2上的Thr73、Gly77、Ile78、Phe84、Gly85、Asp86、Tyr87、Asp79形成多个氢键,以及Ile78、Leu83、Phe84、Asp86、His138、Ile141等形成较强的疏水作用,最终人工挑选得到150个小分子化合物,对接打分值区间为6.58~8.06。抗冻实验结果提示筛选的化合物能够减轻低温对草菇的伤害。Volvariella volvacea is characterized by its cryogenic autolysis.Previous studies showed that cryogenic autolysis is associated with high expression and activity of a ubiquitin-binding enzyme E2(UBEV2).Using the virtual screening method,small molecule inhibitors of V.volvacea UBEV2 were obtained in this study.The results showed that 500 target compounds were obtained using the two-round virtual screening method.These target compounds were further manually selected for those forming multiple hydrogen bonds with Thr73,Gly77,Ile78,Phe84,Gly85,Asp86,Tyr87,and Asp79 of UBEV2,as well as strong hydrophobic interactions with Ile78,Leu83,Phe84,Asp86,His138,and Ile141 of UBEV2.As a result,150 small molecule compounds were picked manually with a docking score range of 6.58-8.06.Two of these compounds,S787-0059 and L345-0044,were then tested in the anti-freezing experiment and showed anti-freezing activity.

关 键 词：草菇 泛素结合酶E2 虚拟筛选 抗冻保鲜 

分 类 号：S646.13[农业科学—蔬菜学]