PDBsum entry 1lm6

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Hydrolase PDB id
Protein chain
191 a.a. *
Waters ×167
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of peptide deformylase from streptococcus
Structure: Peptide deformylase defb. Chain: a. Engineered: yes
Source: Streptococcus pneumoniae. Organism_taxid: 1313. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.75Å     R-factor:   0.208     R-free:   0.256
Authors: A.Kreusch,G.Spraggon,C.C.Lee,H.Klock,D.Mcmullan,K.Ng,T.Shin, J.Vincent,I.Warner,C.Ericson,S.A.Lesley
Key ref:
A.Kreusch et al. (2003). Structure analysis of peptide deformylases from Streptococcus pneumoniae, Staphylococcus aureus, Thermotoga maritima and Pseudomonas aeruginosa: snapshots of the oxygen sensitivity of peptide deformylase. J Mol Biol, 330, 309-321. PubMed id: 12823970 DOI: 10.1016/S0022-2836(03)00596-5
30-Apr-02     Release date:   24-Jun-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q9F2F0  (DEF_STRPN) -  Peptide deformylase
203 a.a.
191 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 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: 10.1016/S0022-2836(03)00596-5 J Mol Biol 330:309-321 (2003)
PubMed id: 12823970  
Structure analysis of peptide deformylases from Streptococcus pneumoniae, Staphylococcus aureus, Thermotoga maritima and Pseudomonas aeruginosa: snapshots of the oxygen sensitivity of peptide deformylase.
A.Kreusch, G.Spraggon, C.C.Lee, H.Klock, D.McMullan, K.Ng, T.Shin, J.Vincent, I.Warner, C.Ericson, S.A.Lesley.
Peptide deformylase (PDF) has received considerable attention during the last few years as a potential target for a new type of antibiotics. It is an essential enzyme in eubacteria for the removal of the formyl group from the N terminus of the nascent polypeptide chain. We have solved the X-ray structures of four members of this enzyme family, two from the Gram-positive pathogens Streptococcus pneumoniae and Staphylococcus aureus, and two from the Gram-negative bacteria Thermotoga maritima and Pseudomonas aeruginosa. Combined with the known structures from the Escherichia coli enzyme and the recently solved structure of the eukaryotic deformylase from Plasmodium falciparum, a complete picture of the peptide deformylase structure and function relationship is emerging. This understanding could help guide a more rational design of inhibitors. A structure-based comparison between PDFs reveals some conserved differences between type I and type II enzymes. Moreover, our structures provide insights into the known instability of PDF caused by oxidation of the metal-ligating cysteine residue.
  Selected figure(s)  
Figure 2.
Figure 2. Ribbon representation of the peptide deformylases from (a) S. aureus, (b) S. pneumoniae, (c) T. maritima, and (d) P. aeruginosa. The color coding is blue (N terminus) to red (C terminus). Metal ions are displayed as solid spheres (purple for S. aureus, S. pneumoniae, red for P. aeruginosa). Please note that the b sheet formed by b4 and b5 is much shorter in type II PDFs than in type I PDFs due to the outward shift of the loop preceeding b5 in type II PDFs.
Figure 4.
Figure 4. Stereo view of (a) the superposition of the metal-binding site of PDF from S. pneumoniae (green) onto T. maritima (light blue), including water molecules common to both structures. The metal ion of the S. pneumoniae protein is shown in red. The conformation of the fully oxidized Cys87 (Cys-SO[3]H) in the T. maritima structure prevents the appropriate binding of a metal ion. The numbering of residues follows the amino acid sequence of S. pneumoniae. (b) Superposition of PDFs from S. pneumoniae (dark blue), S. aureus (light blue), P. aeruginosa (green), and T. maritima (red), respectively. (c) Stereo view of the superposition of the peptide ligand (green carbon atoms) found in the S. aureus structure onto the bound conformations of actinonin (white carbon atoms, PDB code 1G2A) and the tripeptide Met-Ala-Ser (yellow carbon atoms, PDB code BS6). The superposition is based on protein C^a atoms.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2003, 330, 309-321) copyright 2003.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
17936604 A.Balakrishnan, L.Wang, X.Li, P.Ohman-Strickland, P.Malatesta, and H.Fan (2009).
Inhibition of chlamydial infection in the genital tract of female mice by topical application of a peptide deformylase inhibitor.
  Microbiol Res, 164, 338-346.  
19236878 S.Escobar-Alvarez, Y.Goldgur, G.Yang, O.Ouerfelli, Y.Li, and D.A.Scheinberg (2009).
Structure and activity of human mitochondrial peptide deformylase, a novel cancer target.
  J Mol Biol, 387, 1211-1228.
PDB codes: 3g5k 3g5p
18574247 R.Saxena, P.Kanudia, M.Datt, H.H.Dar, S.Karthikeyan, B.Singh, and P.K.Chakraborti (2008).
Three consecutive arginines are important for the mycobacterial Peptide deformylase enzyme activity.
  J Biol Chem, 283, 23754-23764.  
17220413 C.R.Dean, S.Narayan, J.Richards, D.M.Daigle, S.Esterow, J.A.Leeds, H.Kamp, X.Puyang, B.Wiedmann, D.Mueller, H.Voshol, J.van Oostrum, D.Wall, J.Koehn, J.Dzink-Fox, and N.S.Ryder (2007).
Reduced susceptibility of Haemophilus influenzae to the peptide deformylase inhibitor LBM415 can result from target protein overexpression due to amplified chromosomal def gene copy number.
  Antimicrob Agents Chemother, 51, 1004-1010.  
17977509 K.T.Nguyen, J.C.Wu, J.A.Boylan, F.C.Gherardini, and D.Pei (2007).
Zinc is the metal cofactor of Borrelia burgdorferi peptide deformylase.
  Arch Biochem Biophys, 468, 217-225.  
16049914 J.H.Moon, J.K.Park, and E.E.Kim (2005).
Structure analysis of peptide deformylase from Bacillus cereus.
  Proteins, 61, 217-220.
PDB codes: 1ws0 1ws1
  16508119 J.K.Park, J.H.Moon, J.H.Kim, and E.E.Kim (2005).
Crystallization and preliminary X-ray crystallographic analysis of peptide deformylase (PDF) from Bacillus cereus in ligand-free and actinonin-bound forms.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 150-152.  
15629931 K.Vido, H.Diemer, A.Van Dorsselaer, E.Leize, V.Juillard, A.Gruss, and P.Gaudu (2005).
Roles of thioredoxin reductase during the aerobic life of Lactococcus lactis.
  J Bacteriol, 187, 601-610.  
16291698 R.Saxena, and P.K.Chakraborti (2005).
Identification of regions involved in enzymatic stability of peptide deformylase of Mycobacterium tuberculosis.
  J Bacteriol, 187, 8216-8220.  
16239225 Z.Zhou, X.Song, and W.Gong (2005).
Novel conformational states of peptide deformylase from pathogenic bacterium Leptospira interrogans: implications for population shift.
  J Biol Chem, 280, 42391-42396.
PDB codes: 1sv2 1szz 1vev 1vey 1vez
15382235 H.J.Yoon, H.L.Kim, S.K.Lee, H.W.Kim, H.W.Kim, J.Y.Lee, B.Mikami, and S.W.Suh (2004).
Crystal structure of peptide deformylase from Staphylococcus aureus in complex with actinonin, a naturally occurring antibacterial agent.
  Proteins, 57, 639-642.
PDB codes: 1ix1 1q1y
15213398 M.Kamo, N.Kudo, W.C.Lee, H.Motoshima, and M.Tanokura (2004).
Crystallization and preliminary X-ray crystallographic analysis of peptide deformylase from Thermus thermophilus HB8.
  Acta Crystallogr D Biol Crystallogr, 60, 1299-1300.  
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. Where a reference describes a PDB structure, the PDB codes are shown on the right.