PDBsum entry 1bs4

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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
Protein chains
168 a.a. *
2PE ×3
SO4 ×2
_ZN ×3
Waters ×211
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Peptide deformylase as zn2+ containing form (native) in complex with inhibitor polyethylene glycol
Structure: Protein (peptide deformylase). Chain: a, b, c. Synonym: pdf. Engineered: yes. Other_details: pdf protein from escherichia coli is crystallized as zn2+ containing form, cocrystallized with inhibitor polyethylene glycol (peg)
Source: Escherichia coli. Organism_taxid: 562. Strain: jm109. Cellular_location: cytoplasma. Gene: def. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Monomer (from PDB file)
1.90Å     R-factor:   0.193     R-free:   0.240
Authors: A.Becker,I.Schlichting,W.Kabsch,D.Groche,S.Schultz, A.F.V.Wagner
Key ref:
A.Becker et al. (1998). Iron center, substrate recognition and mechanism of peptide deformylase. Nat Struct Biol, 5, 1053-1058. PubMed id: 9846875 DOI: 10.1038/4162
01-Sep-98     Release date:   27-Aug-99    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P0A6K3  (DEF_ECOLI) -  Peptide deformylase
169 a.a.
168 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   3 terms 
  Biochemical function     protein binding     8 terms  


DOI no: 10.1038/4162 Nat Struct Biol 5:1053-1058 (1998)
PubMed id: 9846875  
Iron center, substrate recognition and mechanism of peptide deformylase.
A.Becker, I.Schlichting, W.Kabsch, D.Groche, S.Schultz, A.F.Wagner.
Eubacterial proteins are synthesized with a formyl group at the N-terminus which is hydrolytically removed from the nascent chain by the mononuclear iron enzyme peptide deformylase. Catalytic efficiency strongly depends on the identity of the bound metal. We have determined by X-ray crystallography the Fe2+, Ni2+ and Zn2+ forms of the Escherichia coli enzyme and a structure in complex with the reaction product Met-Ala-Ser. The structure of the complex, with the tripeptide bound at the active site, suggests detailed models for the mechanism of substrate recognition and catalysis. Differences of the protein structures due to the identity of the bound metal are extremely small and account only for the observation that Zn2+ binds more tightly than Fe2+ or Ni2+. The striking loss of catalytic activity of the Zn2+ form could be caused by its reluctance to change between tetrahedral and five-fold metal coordination believed to occur during catalysis. N-terminal formylation and subsequent deformylation
  Selected figure(s)  
Figure 1.
Figure 1. a, Omit map of Met-Ala-Ser in the PDF−Ni/MAS structure contoured at 1 . Figure prepared with BobScript^25. b, Stereo-view of superimposed C -traces of the three crystallographically independent copies of peptide deformylase in complex with the reaction product Met-Ala-Ser. The numbers refer to amino acid residues. The transformations for optimal superposition were determined from equivalent C -atoms using molecule A as a reference and applied to the Ni^2+ ion (marked as Ni) and the peptide as well. Molecule complexes A, B, C are shown in green, magenta, blue, respectively. c, Active site of PDF−Ni (monomer A) with bound catalytic product Met-Ala-Ser, ordered water molecules W1, W2 and the Ni^2+ ion. d, A hypothetical model of PDF with bound substrate formyl-Met-Ala-Ser.
Figure 2.
Figure 2. Peptide deformylase in complex with the reaction product Met-Ala-Ser. a, Peptide binding scheme; Gly 45, Glu 88, Gly 89, His 132 and Glu 133 are conserved residues. Dashed lines indicate hydrogen bonds. Mean distances between donor and acceptor atoms as observed in the three crystallographically independent monomers are given in Å . The distance between the N-terminal amino group of the peptide to the Ni^2+-ion is 3.9 Å. b, Protein atoms (white, carbon; red, oxygen; dark blue, nitrogen; green, sulphur) and catalytic metal (magenta, Ni^2+) are depicted as space-filling spheres. Met-Ala-Ser is in ball-and-stick representation with carbon atoms and bonds colored yellow. Water molecules W1, W2 are shown as small light blue spheres. Figure prepared using MOLSCRIPT^26 and Raster3D^27.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (1998, 5, 1053-1058) copyright 1998.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19922819 A.K.Berg, Q.Yu, S.Y.Qian, M.K.Haldar, and D.K.Srivastava (2010).
Solvent-assisted slow conversion of a dithiazole derivative produces a competitive inhibitor of peptide deformylase.
  Biochim Biophys Acta, 1804, 704-713.  
20136146 M.Hernick, S.G.Gattis, J.E.Penner-Hahn, and C.A.Fierke (2010).
Activation of Escherichia coli UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase by Fe2+ yields a more efficient enzyme with altered ligand affinity.
  Biochemistry, 49, 2246-2255.  
19191548 A.K.Berg, and D.K.Srivastava (2009).
Delineation of alternative conformational states in Escherichia coli peptide deformylase via thermodynamic studies for the binding of actinonin.
  Biochemistry, 48, 1584-1594.  
19627112 C.D.Amero, D.W.Byerly, C.A.McElroy, A.Simmons, and M.P.Foster (2009).
Ligand-induced changes in the structure and dynamics of Escherichia coli peptide deformylase.
  Biochemistry, 48, 7595-7607.  
18781344 C.Y.Huang, C.C.Hsu, M.C.Chen, and Y.S.Yang (2009).
Effect of metal binding and posttranslational lysine carboxylation on the activity of recombinant hydantoinase.
  J Biol Inorg Chem, 14, 111-121.  
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
18400172 M.Selmer, and A.Liljas (2008).
Exit biology: battle for the nascent chain.
  Structure, 16, 498-500.  
18400179 P.Koenig, M.Oreb, A.Höfle, S.Kaltofen, K.Rippe, I.Sinning, E.Schleiff, and I.Tews (2008).
The GTPase cycle of the chloroplast import receptors Toc33/Toc34: implications from monomeric and dimeric structures.
  Structure, 16, 585-596.
PDB codes: 3bb1 3bb3 3bb4
  18997334 P.T.Ngo, J.K.Kim, H.Kim, J.Jung, Y.J.Ahn, J.G.Kim, B.M.Lee, and L.W.Kang (2008).
Expression, crystallization and preliminary X-ray crystallographic analysis of peptide deformylase from Xanthomonas oryzae pv. oryzae.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 1031-1033.  
18288106 R.Bingel-Erlenmeyer, R.Kohler, G.Kramer, A.Sandikci, S.Antolić, T.Maier, C.Schaffitzel, B.Wiedmann, B.Bukau, and N.Ban (2008).
A peptide deformylase-ribosome complex reveals mechanism of nascent chain processing.
  Nature, 452, 108-111.
PDB codes: 2vhm 2vhn 2vho 2vhp
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.  
18234665 S.Ravaud, G.Stjepanovic, K.Wild, and I.Sinning (2008).
The crystal structure of the periplasmic domain of the Escherichia coli membrane protein insertase YidC contains a substrate binding cleft.
  J Biol Chem, 283, 9350-9358.
PDB code: 3bs6
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.  
16645816 G.J.Kornhaber, D.Snyder, H.N.Moseley, and G.T.Montelione (2006).
Identification of zinc-ligated cysteine residues based on 13Calpha and 13Cbeta chemical shift data.
  J Biomol NMR, 34, 259-269.  
16471944 V.V.Karambelkar, C.Xiao, Y.Zhang, A.A.Sarjeant, and D.P.Goldberg (2006).
Geometric preferences in iron(II) and zinc(II) model complexes of peptide deformylase.
  Inorg Chem, 45, 1409-1411.  
16192279 S.Fieulaine, C.Juillan-Binard, A.Serero, F.Dardel, C.Giglione, T.Meinnel, and J.L.Ferrer (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.
PDB codes: 1zxz 1zy0 1zy1
14693547 D.Chen, C.Hackbarth, Z.J.Ni, C.Wu, W.Wang, R.Jain, Y.He, K.Bracken, B.Weidmann, D.V.Patel, J.Trias, R.J.White, and Z.Yuan (2004).
Peptide deformylase inhibitors as antibacterial agents: identification of VRC3375, a proline-3-alkylsuccinyl hydroxamate derivative, by using an integrated combinatorial and medicinal chemistry approach.
  Antimicrob Agents Chemother, 48, 250-261.  
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.  
12888556 O.Pylypenko, F.Vitali, K.Zerbe, J.A.Robinson, and I.Schlichting (2003).
Crystal structure of OxyC, a cytochrome P450 implicated in an oxidative C-C coupling reaction during vancomycin biosynthesis.
  J Biol Chem, 278, 46727-46733.
PDB code: 1ued
12005434 A.Kumar, K.T.Nguyen, S.Srivathsan, B.Ornstein, S.Turley, I.Hirsh, D.Pei, and W.G.Hol (2002).
Crystals of peptide deformylase from Plasmodium falciparum reveal critical characteristics of the active site for drug design.
  Structure, 10, 357-367.
PDB code: 1jym
12183225 C.J.Hackbarth, D.Z.Chen, J.G.Lewis, K.Clark, J.B.Mangold, J.A.Cramer, P.S.Margolis, W.Wang, J.Koehn, C.Wu, S.Lopez, G.Withers, H.Gu, E.Dunn, R.Kulathila, S.H.Pan, W.L.Porter, J.Jacobs, J.Trias, D.V.Patel, B.Weidmann, R.J.White, and Z.Yuan (2002).
N-alkyl urea hydroxamic acids as a new class of peptide deformylase inhibitors with antibacterial activity.
  Antimicrob Agents Chemother, 46, 2752-2764.  
12048187 E.T.Baldwin, M.S.Harris, A.W.Yem, C.L.Wolfe, A.F.Vosters, K.A.Curry, R.W.Murray, J.H.Bock, V.P.Marshall, J.I.Cialdella, M.H.Merchant, G.Choi, and M.R.Deibel (2002).
Crystal structure of type II peptide deformylase from Staphylococcus aureus.
  J Biol Chem, 277, 31163-31171.
PDB code: 1lmh
15992166 D.Pei (2001).
Peptide deformylase: a target for novel antibiotics?
  Expert Opin Ther Targets, 5, 23-40.  
11158755 J.M.Clements, R.P.Beckett, A.Brown, G.Catlin, M.Lobell, S.Palan, W.Thomas, M.Whittaker, S.Wood, S.Salama, P.J.Baker, H.F.Rodgers, V.Barynin, D.W.Rice, and M.G.Hunter (2001).
Antibiotic activity and characterization of BB-3497, a novel peptide deformylase inhibitor.
  Antimicrob Agents Chemother, 45, 563-570.
PDB codes: 1g27 1g2a
11502510 P.Margolis, C.Hackbarth, S.Lopez, M.Maniar, W.Wang, Z.Yuan, R.White, and J.Trias (2001).
Resistance of Streptococcus pneumoniae to deformylase inhibitors is due to mutations in defB.
  Antimicrob Agents Chemother, 45, 2432-2435.  
11546610 Z.Yuan, J.Trias, and R.J.White (2001).
Deformylase as a novel antibacterial target.
  Drug Discov Today, 6, 954-961.  
10931273 C.Giglione, M.Pierre, and T.Meinnel (2000).
Peptide deformylase as a target for new generation, broad spectrum antimicrobial agents.
  Mol Microbiol, 36, 1197-1205.  
10684604 D.Z.Chen, D.V.Patel, C.J.Hackbarth, W.Wang, G.Dreyer, D.C.Young, P.S.Margolis, C.Wu, Z.J.Ni, J.Trias, R.J.White, and Z.Yuan (2000).
Actinonin, a naturally occurring antibacterial agent, is a potent deformylase inhibitor.
  Biochemistry, 39, 1256-1262.  
10758004 K.M.Huntington, T.Yi, Y.Wei, and D.Pei (2000).
Synthesis and antibacterial activity of peptide deformylase inhibitors.
  Biochemistry, 39, 4543-4551.  
10858337 P.S.Margolis, C.J.Hackbarth, D.C.Young, W.Wang, D.Chen, Z.Yuan, R.White, and J.Trias (2000).
Peptide deformylase in Staphylococcus aureus: resistance to inhibition is mediated by mutations in the formyltransferase gene.
  Antimicrob Agents Chemother, 44, 1825-1831.  
10651644 P.T.Rajagopalan, S.Grimme, and D.Pei (2000).
Characterization of cobalt(II)-substituted peptide deformylase: function of the metal ion and the catalytic residue Glu-133.
  Biochemistry, 39, 779-790.  
  10595562 K.S.Makarova, and N.V.Grishin (1999).
Thermolysin and mitochondrial processing peptidase: how far structure-functional convergence goes.
  Protein Sci, 8, 2537-2540.  
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.