PDBsum entry 2ew6

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Hydrolase PDB id
Protein chain
166 a.a. *
Waters ×128
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Structure of helicobacter pylori peptide deformylase in complex with inhibitor
Structure: Peptide deformylase. Chain: a. Engineered: yes
Source: Helicobacter pylori. Organism_taxid: 210. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
2.20Å     R-factor:   0.204     R-free:   0.243
Authors: J.Cai
Key ref:
J.Cai et al. (2006). 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. PubMed id: 16882991 DOI: 10.1110/ps.062238406
02-Nov-05     Release date:   24-Oct-06    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q672W7  (Q672W7_HELPX) -  Peptide deformylase
174 a.a.
166 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Peptide deformylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Formyl-L-methionyl peptide + H2O = formate + methionyl peptide
Formyl-L-methionyl peptide
+ H(2)O
= formate
+ methionyl peptide
      Cofactor: Fe(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     translation   1 term 
  Biochemical function     hydrolase activity     4 terms  


DOI no: 10.1110/ps.062238406 Protein Sci 15:2071-2081 (2006)
PubMed id: 16882991  
Peptide deformylase is a potential target for anti-Helicobacter pylori drugs: reverse docking, enzymatic assay, and X-ray crystallography validation.
J.Cai, C.Han, T.Hu, J.Zhang, D.Wu, F.Wang, Y.Liu, J.Ding, K.Chen, J.Yue, X.Shen, H.Jiang.
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, 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.
  Selected figure(s)  
Figure 6.
Figure 6. Bindings of compounds 1 and 2 to HpPDF. (A) Comparison of the conformations of compounds 1 and 2 in the binding
  The above figure is reprinted by permission from the Protein Society: Protein Sci (2006, 15, 2071-2081) copyright 2006.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20808948 E.Defranchi, E.De Franchi, C.Schalon, M.Messa, F.Onofri, F.Benfenati, and D.Rognan (2010).
Binding of protein kinase inhibitors to synapsin I inferred from pair-wise binding site similarity measurements.
  PLoS One, 5, e12214.  
21058655 M.J.Keiser, J.J.Irwin, and B.K.Shoichet (2010).
The chemical basis of pharmacology.
  Biochemistry, 49, 10267-10276.  
20656778 P.Lin, T.Hu, J.Hu, W.Yu, C.Han, J.Zhang, G.Qin, K.Yu, F.Götz, X.Shen, H.Jiang, and D.Qu (2010).
Characterization of peptide deformylase homologues from Staphylococcus epidermidis.
  Microbiology, 156, 3194-3202.  
20594344 R.R.Thangudu, M.Tyagi, B.A.Shoemaker, S.H.Bryant, A.R.Panchenko, and T.Madej (2010).
Knowledge-based annotation of small molecule binding sites in proteins.
  BMC Bioinformatics, 11, 365.  
19735225 M.J.Duckworth, A.S.Okoli, and G.L.Mendz (2009).
Novel Helicobacter pylori therapeutic targets: the unusual suspects.
  Expert Rev Anti Infect Ther, 7, 835-867.  
19346246 Z.Zhou, Y.Hashimoto, and M.Kobayashi (2009).
Self-subunit Swapping Chaperone Needed for the Maturation of Multimeric Metalloenzyme Nitrile Hydratase by a Subunit Exchange Mechanism Also Carries Out the Oxidation of the Metal Ligand Cysteine Residues and Insertion of Cobalt.
  J Biol Chem, 284, 14930-14938.  
18282303 Z.Gao, H.Li, H.Zhang, X.Liu, L.Kang, X.Luo, W.Zhu, K.Chen, X.Wang, and H.Jiang (2008).
PDTD: a web-accessible protein database for drug target identification.
  BMC Bioinformatics, 9, 104.  
18033577 D.D.Baker, M.Chu, U.Oza, and V.Rajgarhia (2007).
The value of natural products to future pharmaceutical discovery.
  Nat Prod Rep, 24, 1225-1244.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.