2EW5

Structure of Helicobacter Pylori peptide deformylase in complex with inhibitor

2EW5 の概要

• エントリーDOI: 10.2210/pdb2ew5/pdb
• 関連するPDBエントリー: 2EW6 2EW7
• 分子名称: peptide deformylase, COBALT (II) ION, 4-{(1E)-3-OXO-3-[(2-PHENYLETHYL)AMINO]PROP-1-EN-1-YL}-1,2-PHENYLENE DIACETATE, ... (4 entities in total)
• 機能のキーワード: cobalt helicobacter pylori peptide deformylase, inhibitor, hydrolase
• 由来する生物種: Helicobacter pylori
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 21434.79

構造登録者

Cai, J. (登録日: 2005-11-02, 公開日: 2006-10-24, 最終更新日: 2023-10-25)

主引用文献

Cai, J.,Han, C.,Hu, T.,Zhang, J.,Wu, D.,Wang, F.,Liu, Y.,Ding, J.,Chen, K.,Yue, J.,Shen, X.,Jiang, H.
Peptide deformylase is a potential target for anti-Helicobacter pylori drugs: reverse docking, enzymatic assay, and X-ray crystallography validation
Protein Sci., 15:2071-2081, 2006

PubMed Abstract: 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 microM, 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.

PubMed: 16882991
DOI: 10.1110/ps.062238406

実験手法

X-RAY DIFFRACTION (2.2 Å)