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学科主题: 药学
题名:
Computational investigation of interactions between Cdc37 and celastrol
作者: 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
发表日期: 2013-04-01
DOI: 10.1080/08927022.2012.718439
卷: 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
所属项目编号: 2011BS1201 ; 20902068 ; 20972010
项目资助者: Natural Science Foundation of Inner Mongolia Autonomous Region, China ; National Natural Science Foundation of China
WOS记录号: WOS:000315942900003
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51769
Appears in Collections:北京大学药学院_期刊论文

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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

Recommended Citation:
Duan, Yaokai,Jin, Hongwei,Yu, Hui,et al. Computational investigation of interactions between Cdc37 and celastrol[J]. MOLECULAR SIMULATION,2013,39(4):270-278.
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