Peptide deformylase is a potential target for anti-Helicobacter pylori drugs: Reverse docking, enzymatic assay, and X-ray crystallography validation

doi:10.1110/ps.062238406

IMR OpenIR

	Peptide deformylase is a potential target for anti-Helicobacter pylori drugs: Reverse docking, enzymatic assay, and X-ray crystallography validation
	Cai, Jianhua ; Han, Cong ; Hu, Tiancen ; Zhang, Jian ; Wu, Dalei ; Wang, Fangdao ; Liu, Yunqing ; Ding, Jianping ; Chen, Kaixian ; Yue, Jianmin ; Shen, Xu ; Jiang, Hualiang
通讯作者	Shen, Xu(xshen@mail.shcnc.ac.cn)
	2006-09-01
发表期刊	PROTEIN SCIENCE
ISSN	0961-8368
卷号	15 期号:9 页码:2071-2081
摘要	Colonization of human stomach by the bacterium Helicobacter pylori is a major causative factor for gastrointestinal illnesses and gastric cancer. However, the discovery of anti-H. pylori agents is a difficult task due to lack of mature protein targets. Therefore, identifying new molecular targets for developing new drugs against H. pylori is obviously necessary. In this study, the in-house potential drug target database (PDTD, http://www.dddc.ac.cn/tarfisdock/) was searched by the reverse docking approach using an active natural product (compound 1) discovered by anti-H. pylori screening as a probe. Homology search revealed that, among the 15 candidates discovered by reverse docking, only diaminopimelate decarboxylase (DC) and peptide deformylase (PDF) have homologous proteins in the genome of H. pylori. Enzymatic assay demonstrated compound 1 and its derivative compound 2 are the potent inhibitors against H. pylori PDF (HpPDF) with IC50 values of 10.8 and 1.25 mu M, respectively. X-ray crystal structures of HpPDF and the complexes of HpPDF with 1 and 2 were determined for the first time, indicating that these two inhibitors bind well with HpPDF binding pocket. All these results indicate that HpPDF is a potential target for screening new anti-H. pylori agents. In addition, compounds 1 and 2 were predicted to bind to HpPDF with relatively high selectivity, suggesting they can be used as leads for developing new anti-H. pylori agents. The results demonstrated that our strategy, reverse docking in conjunction with bioassay and structural biology, is effective and can be used as a complementary approach of functional genomics and chemical biology in target identification.
关键词	peptide deformylase protein crystallization reverse docking enzyme inhibitor Helicobacter pylori
DOI	10.1110/ps.062238406
收录类别	SCI
语种	英语
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000240156400005
出版者	COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
引用统计	被引频次：77[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.imr.ac.cn/handle/321006/88120
专题	中国科学院金属研究所
通讯作者	Shen, Xu
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci, Grad Sch Chinese Acad Sci, Shanghai Inst Mat Med,State Key Lab Drug Res,Drug, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Key Lab Prot, Shanghai 200031, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China 4.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
推荐引用方式 GB/T 7714	Cai, Jianhua,Han, Cong,Hu, Tiancen,et al. Peptide deformylase is a potential target for anti-Helicobacter pylori drugs: Reverse docking, enzymatic assay, and X-ray crystallography validation[J]. PROTEIN SCIENCE,2006,15(9):2071-2081.
APA	Cai, Jianhua.,Han, Cong.,Hu, Tiancen.,Zhang, Jian.,Wu, Dalei.,...&Jiang, Hualiang.(2006).Peptide deformylase is a potential target for anti-Helicobacter pylori drugs: Reverse docking, enzymatic assay, and X-ray crystallography validation.PROTEIN SCIENCE,15(9),2071-2081.
MLA	Cai, Jianhua,et al."Peptide deformylase is a potential target for anti-Helicobacter pylori drugs: Reverse docking, enzymatic assay, and X-ray crystallography validation".PROTEIN SCIENCE 15.9(2006):2071-2081.