Break CDK2/Cyclin E1 Interface Allosterically with Small Peptides

doi:10.1371/journal.pone.0109154

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	Break CDK2/Cyclin E1 Interface Allosterically with Small Peptides
	Chen, Hao 2; Zhao, Yunjie 2; Li, Haotian 1; Zhang, Dongyan 1; Huang, Yanzhao 1; Shen, Qi 3; Van Duyne, Rachel 4,5; Kashanchi, Fatah 4; Zeng, Chen 1,2; Liu, Shiyong 1
刊名	PLOS ONE
	2014-10-07
卷号	9 期号:10
ISSN号	1932-6203
DOI	10.1371/journal.pone.0109154
英文摘要	Most inhibitors of Cyclin-dependent kinase 2 (CDK2) target its ATP-binding pocket. It is difficult, however, to use this pocket to design very specific inhibitors because this catalytic pocket is highly conserved in the protein family of CDKs. Here we report some short peptides targeting a noncatalytic pocket near the interface of the CDK2/Cyclin complex. Docking and molecular dynamics simulations were used to select the peptides, and detailed dynamical network analysis revealed that these peptides weaken the complex formation via allosteric interactions. Our experiments showed that upon binding to the noncatalytic pocket, these peptides break the CDK2/Cyclin complex partially and diminish its kinase activity in vitro. The binding affinity of these peptides measured by Surface Plasmon Resonance can reach as low as 0.5 mu M.
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000342798000040
内容类型	期刊论文
源URL	[http://ir.iccas.ac.cn/handle/121111/51279]
专题	中国科学院化学研究所
通讯作者	Liu, Shiyong
作者单位	1.Huazhong Univ Sci & Technol, Dept Phys, Wuhan 430074, Hubei, Peoples R China 2.George Washington Univ, Dept Phys, Washington, DC 20052 USA 3.Peking Univ, Ctr Quantitat Biol, BNLMS, Beijing 100871, Peoples R China 4.George Mason Univ, Natl Ctr Biodefense & Infect Dis, Manassas, VA USA 5.George Washington Univ, Med Ctr, Dept Microbiol Immunol & Trop Med, Washington, DC 20037 USA
推荐引用方式 GB/T 7714	Chen, Hao,Zhao, Yunjie,Li, Haotian,et al. Break CDK2/Cyclin E1 Interface Allosterically with Small Peptides[J]. PLOS ONE,2014,9(10).
APA	Chen, Hao.,Zhao, Yunjie.,Li, Haotian.,Zhang, Dongyan.,Huang, Yanzhao.,...&Liu, Shiyong.(2014).Break CDK2/Cyclin E1 Interface Allosterically with Small Peptides.PLOS ONE,9(10).
MLA	Chen, Hao,et al."Break CDK2/Cyclin E1 Interface Allosterically with Small Peptides".PLOS ONE 9.10(2014).