2ew5: Difference between revisions
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[[Image:2ew5.gif|left|200px]] | [[Image:2ew5.gif|left|200px]] | ||
'''Structure of Helicobacter Pylori peptide deformylase in complex with inhibitor''' | {{Structure | ||
|PDB= 2ew5 |SIZE=350|CAPTION= <scene name='initialview01'>2ew5</scene>, resolution 2.2Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene> and <scene name='pdbligand=Y12:4-{(1E)-3-OXO-3-[(2-PHENYLETHYL)AMINO]PROP-1-EN-1-YL}-1,2-PHENYLENE DIACETATE'>Y12</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Peptide_deformylase Peptide deformylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.88 3.5.1.88] | |||
|GENE= | |||
}} | |||
'''Structure of Helicobacter Pylori peptide deformylase in complex with inhibitor''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2EW5 is a [ | 2EW5 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Helicobacter_pylori Helicobacter pylori]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EW5 OCA]. | ||
==Reference== | ==Reference== | ||
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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/16882991 16882991] | ||
[[Category: Helicobacter pylori]] | [[Category: Helicobacter pylori]] | ||
[[Category: Peptide deformylase]] | [[Category: Peptide deformylase]] | ||
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[[Category: inhibitor]] | [[Category: inhibitor]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:45:07 2008'' | ||
Revision as of 17:45, 20 March 2008
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| , resolution 2.2Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Activity: | Peptide deformylase, with EC number 3.5.1.88 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of Helicobacter Pylori peptide deformylase in complex with inhibitor
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
2EW5 is a Single protein structure of sequence from Helicobacter pylori. 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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