2ew7
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Crystal Structure of Helicobacter Pylori peptide deformylase
OverviewOverview
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.
About this StructureAbout this Structure
2EW7 is a Single protein structure of sequence from Helicobacter pylori with as ligand. Active as Peptide deformylase, with EC number 3.5.1.88 Full crystallographic information is available from OCA.
ReferenceReference
Peptide deformylase is a potential target for anti-Helicobacter pylori drugs: reverse docking, enzymatic assay, and X-ray crystallography validation., Cai J, Han C, Hu T, Zhang J, Wu D, Wang F, Liu Y, Ding J, Chen K, Yue J, Shen X, Jiang H, Protein Sci. 2006 Sep;15(9):2071-81. Epub 2006 Aug 1. PMID:16882991
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