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Computational investigation of interactions between Cdc37 and celastrol
Duan, Yaokai1; Jin, Hongwei1; Yu, Hui2; Wang, Zhanli3; Zhang, Liangren1; Huo, Jianxin3
关键词Cdc37 Celastrol Inhibitor Homology Modelling Docking Dynamics Simulation
刊名MOLECULAR SIMULATION
2013-04-01
DOI10.1080/08927022.2012.718439
39期:4页:270-278
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Physical ; Physics, Atomic, Molecular & Chemical
研究领域[WOS]Chemistry ; Physics
关键词[WOS]PROTEIN-KINASE-BINDING ; MOLECULAR-DYNAMICS ; GENETIC ALGORITHM ; HSP90 ; SIMULATIONS ; COCHAPERONE ; INHIBITION ; MECHANISM ; COMPLEX ; DOMAIN
英文摘要

Celastrol is a novel inhibitor of the human protein complex Hsp90Cdc37. It was found that the N-terminal domain of Cdc37 (Cdc37_N) was the molecular target for celastrol binding through covalent bonding. To get insight into the binding mode of celastrol in the active site of Cdc37, herein, the homology models of Cdc37_N and N-terminal/middle domain of Cdc37 (Cdc37_NM) were built. Moreover, a model of Cdc37 complexed with celastrol was obtained using docking and molecular dynamics (MD) approaches. Molecular modelling studies indicated that the middle domain of Cdc37 (Cdc37_M) might be an obbligato part of the binding pocket, which could make the pocket stable for celastrol docking. We also found that the S atom of Cys57 was closest to C6 atom of celastrol among all three cysteine residues (Cys54, Cys57 and Cys64) in the pocket, which implied that celastrol and Cys57 did have a good chance to form covalent bond. The covalent interaction between C6 atom of celastrol and Cys57 of Cdc37 could also explain the potency of celastrol to inhibit the interaction of Cdc37 and Hsp90. These findings can be used to develop novel Cdc37 inhibitors.

语种英语
WOS记录号WOS:000315942900003
项目编号2011BS1201 ; 20902068 ; 20972010
资助机构Natural Science Foundation of Inner Mongolia Autonomous Region, China ; National Natural Science Foundation of China
引用统计
被引频次:3[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51769
专题北京大学药学院
北京大学药学院_天然药物与仿生药物国家重点实验室
北京大学药学院_药物化学系
作者单位1.Peking Univ, State Key Lab Nat & Biomimet Drugs, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
2.Second Affiliated Hosp, Baotou Med Coll, Baotou 014010, Peoples R China
3.First Affiliated Hosp, Baotou Med Coll, Baotou 014010, Peoples R China
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GB/T 7714
Duan, Yaokai,Jin, Hongwei,Yu, Hui,et al. Computational investigation of interactions between Cdc37 and celastrol[J]. MOLECULAR SIMULATION,2013,39(4):270-278.
APA Duan, Yaokai,Jin, Hongwei,Yu, Hui,Wang, Zhanli,Zhang, Liangren,&Huo, Jianxin.(2013).Computational investigation of interactions between Cdc37 and celastrol.MOLECULAR SIMULATION,39(4),270-278.
MLA Duan, Yaokai,et al."Computational investigation of interactions between Cdc37 and celastrol".MOLECULAR SIMULATION 39.4(2013):270-278.
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