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

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	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
刊名	PROTEIN SCIENCE
	2006-09
卷号	15 期号:9 页码:2071-2081
关键词	peptide deformylase protein crystallization reverse docking enzyme inhibitor Helicobacter pylori
ISSN号	0961-8368
DOI	10.1110/ps.062238406
文献子类	Article
英文摘要	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.
WOS关键词	SPECTROPHOTOMETRIC ASSAY ; ANTIBIOTIC-RESISTANCE ; DESIGN ; ERADICATION ; ACTINONIN ; IDENTIFICATION ; INHIBITION ; AGENTS
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
WOS记录号	WOS:000240156400005
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273515]
专题	天然药物化学研究室中科院受体结构与功能重点实验室新药研究国家重点实验室药物发现与设计中心药理学第三研究室
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.