Peptide deformylase is a potential target for anti-Helicobacter pylori drugs: Reverse docking, enzymatic assay, and X-ray crystallography validation
文献类型：期刊论文
| 作者 | Cai, Jianhua; Han, Cong; Hu, Tiancen; Zhang, Jian; Wu, Dalei; Wang, Fangdao; Liu, Yunqing; Ding, Jianping; Chen, Kaixian; Yue, Jianmin |
| 刊名 | PROTEIN SCIENCE
 |
| 出版日期 | 2006-09-01 |
| 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 |
| 通讯作者 | Shen, Xu(xshen@mail.shcnc.ac.cn) |
| 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研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000240156400005 |
| 出版者 | COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT |
| 源URL | [http://ir.imr.ac.cn/handle/321006/88119]  |
| 专题 | 金属研究所_中国科学院金属研究所 |
| 通讯作者 | Shen, Xu |
| 作者单位 | 1.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China 2.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 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Key Lab Prot, Shanghai 200031, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, 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. |
入库方式： OAI收割
来源：金属研究所
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