PDBsum entry 1zxz

Go to PDB code: 
protein metals Protein-protein interface(s) links
Hydrolase PDB id
Jmol PyMol
Protein chains
192 a.a. *
_ZN ×2
Waters ×210
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: X-ray structure of peptide deformylase from arabidopsis thaliana (atpdf1a); crystals grown in peg-5000 mme as precipitant
Structure: Peptide deformylase, mitochondrial. Chain: a, b. Fragment: mature protein. Synonym: pdf. Polypeptide deformylase. Engineered: yes
Source: Arabidopsis thaliana. Thale cress. Organism_taxid: 3702. Gene: pdf1a. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
2.80Å     R-factor:   0.236     R-free:   0.291
Authors: S.Fieulaine,C.Juillan-Binard,A.Serero,F.Dardel,C.Giglione, T.Meinnel,J.-L.Ferrer
Key ref:
S.Fieulaine et al. (2005). The crystal structure of mitochondrial (Type 1A) peptide deformylase provides clear guidelines for the design of inhibitors specific for the bacterial forms. J Biol Chem, 280, 42315-42324. PubMed id: 16192279 DOI: 10.1074/jbc.M507155200
09-Jun-05     Release date:   27-Sep-05    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q9FV53  (DEF1A_ARATH) -  Peptide deformylase 1A, chloroplastic/mitochondrial
269 a.a.
192 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 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


DOI no: 10.1074/jbc.M507155200 J Biol Chem 280:42315-42324 (2005)
PubMed id: 16192279  
The crystal structure of mitochondrial (Type 1A) peptide deformylase provides clear guidelines for the design of inhibitors specific for the bacterial forms.
S.Fieulaine, C.Juillan-Binard, A.Serero, F.Dardel, C.Giglione, T.Meinnel, J.L.Ferrer.
Peptide deformylase (PDF) inhibitors have a strong potential to be used as a new class of antibiotics. However, recent studies have shown that the mitochondria of most eukaryotes, including humans, contain an essential PDF, PDF1A. The crystal structure of the Arabidopsis thaliana PDF1A (AtPDF1A), considered representative of PDF1As in general, has been determined. This structure displays several similarities to that of known bacterial PDFs. AtPDF1A behaves as a dimer, with the C-terminal residues responsible for linking the two subunits. This arrangement is similar to that of Leptospira interrogans PDF, the only other dimeric PDF identified to date. AtPDF1A is the first PDF for which zinc has been identified as the catalytic ion. However, the zinc binding pocket does not differ from the binding pockets of PDFs with iron rather than zinc. The crystal structure of AtPDF1A in complex with a substrate analog revealed that the substrate binding pocket of PDF1A displays strong modifications. The S1' binding pocket is significantly narrower, due to the creation of a floor from residues present in all PDF1As but not in bacterial PDFs. A true S3' pocket is created by the residues of a helical CD-loop, which is very long in PDF1As. Finally, these modified substrate binding pockets modify the position of the substrate in the active site. These differences provide guidelines for the design of bacterial PDF inhibitors that will not target mitochondrial PDFs.
  Selected figure(s)  
Figure 5.
FIGURE 5. Modeling of the human PDF from the A. thaliana PDF. The structural model of the tripeptide-binding site of HsPDF1A is represented as in Fig. 3C. The Met-Ala-Ser tripeptide is modeled from the complex between Met-Ala-Ser and AtPDF1A H.
Figure 6.
FIGURE 6. Comparison of the substrate-binding sites of PDF1A and PDF1B. The structures of PDF1B (Protein Data Bank entry 1BS6) (18) and PDF1A (A. thaliana) (this work) complexed to the reaction product, peptide Met-Ala-Ser, were used to calculate the solvent-accessible surface of the active site, using a radius of 1.4 Å for the solvent. The two structures were oriented similarly, using the methionine ligand atoms and the metal for local fitting. The ligand is shown as sticks, and the metal ion is shown as a green sphere. PDF1B shows an open S1' pocket, largely open to the solvent, and no S3' site, as opposed to PDF1A, which has a closed S1' pocket and a clear S3' site contributed by the CD-loop insertion specific to mitochondrial PDFs.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 42315-42324) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
19647435 C.Giglione, S.Fieulaine, and T.Meinnel (2009).
Cotranslational processing mechanisms: towards a dynamic 3D model.
  Trends Biochem Sci, 34, 417-426.  
19649280 L.Mamelli, S.Petit, J.Chevalier, C.Giglione, A.Lieutaud, T.Meinnel, I.Artaud, and J.M.Pagès (2009).
New antibiotic molecules: bypassing the membrane barrier of gram negative bacteria increases the activity of peptide deformylase inhibitors.
  PLoS One, 4, e6443.  
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
19053131 S.Petit, Y.Duroc, V.Larue, C.Giglione, C.Léon, C.Soulama, A.Denis, F.Dardel, T.Meinnel, and I.Artaud (2009).
Structure-activity relationship analysis of the peptide deformylase inhibitor 5-bromo-1H-indole-3-acetohydroxamic acid.
  ChemMedChem, 4, 261-275.  
17309682 C.X.Hou, L.M.Dirk, S.Pattanaik, N.C.Das, I.B.Maiti, R.L.Houtz, and M.A.Williams (2007).
Plant peptide deformylase: a novel selectable marker and herbicide target based on essential cotranslational chloroplast protein processing.
  Plant Biotechnol J, 5, 275-281.  
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.  
16733568 F.Namuswe, and D.P.Goldberg (2006).
A combinatorial approach to minimal peptide models of a metalloprotein active site.
  Chem Commun (Camb), (), 2326-2328.  
16597508 L.L.Walling (2006).
Recycling or regulation? The role of amino-terminal modifying enzymes.
  Curr Opin Plant Biol, 9, 227-233.  
16913833 T.Meinnel, A.Serero, and C.Giglione (2006).
Impact of the N-terminal amino acid on targeted protein degradation.
  Biol Chem, 387, 839-851.  
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.