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PDBsum entry 1dff
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protein metals links
Hydrolase PDB id
1dff

 

 

 

 

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Contents
Protein chain
164 a.a. *
Metals
_ZN
Waters ×47
* Residue conservation analysis
PDB id:
1dff
Name: Hydrolase
Title: Peptide deformylase
Structure: Peptide deformylase. Chain: a. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: the details of the expression may be found in biochemistry 36, 13910 (1997)
Resolution:
2.88Å     R-factor:   0.184     R-free:   0.289
Authors: M.K.Chan,W.Gong,P.T.R.Rajagopalan,B.Hao,C.M.Tsai,D.Pei
Key ref:
M.K.Chan et al. (1997). Crystal structure of the Escherichia coli peptide deformylase. Biochemistry, 36, 13904-13909. PubMed id: 9374869 DOI: 10.1021/bi9711543
Date:
19-Aug-97     Release date:   02-Sep-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P0A6K3  (DEF_ECOLI) -  Peptide deformylase from Escherichia coli (strain K12)
Seq:
Struc: 		169 a.a.
164 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.5.1.88  - peptide deformylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: N-terminal N-formyl-L-methionyl-[peptide] + H2O = N-terminal L-methionyl- [peptide] + formate
N-terminal N-formyl-L-methionyl-[peptide]
 + H2O
 = N-terminal L-methionyl- [peptide]
 + formate
      Cofactor: Fe(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Key reference    
 
 
DOI no: 10.1021/bi9711543 Biochemistry 36:13904-13909 (1997)
PubMed id: 9374869  
 
 
Crystal structure of the Escherichia coli peptide deformylase.
M.K.Chan, W.Gong, P.T.Rajagopalan, B.Hao, C.M.Tsai, D.Pei.
 
  ABSTRACT  
 
Protein synthesis in bacteria involves the formylation and deformylation of the N-terminal methionine. As eukaryotic organisms differ in their protein biosynthetic mechanisms, peptide deformylase, the bacterial enzyme responsible for deformylation, represents a potential target for antibiotic studies. Here we report the crystallization and 2.9 A X-ray structure solution of the zinc containing Escherichia coli peptide deformylase. While the primary sequence, tertiary structure, and use of coordinated cysteine suggest that E. coli deformylase belongs to a new subfamily of metalloproteases, the environment around the metal appears to have strong geometric similarity to the active sites of the thermolysin family. This suggests a possible similarity in their hydrolytic mechanisms. Another important issue is the origin of the enzyme's specificity for N-formylated over N-acetylated substrates. Based on the structure, the specificity appears to result from hydrogen-bonding interactions which orient the substrate for cleavage, and steric factors which physically limit the size of the N-terminal carbonyl group.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
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.  
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.  
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
18042674 A.K.Berg, S.Manokaran, D.Eiler, J.Kooren, S.Mallik, and D.K.Srivastava (2008).
Energetic rationale for an unexpected and abrupt reversal of guanidinium chloride-induced unfolding of peptide deformylase.
  Protein Sci, 17, 11-15.  
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.  
16966397 J.W.Teo, P.Thayalan, D.Beer, A.S.Yap, M.Nanjundappa, X.Ngew, J.Duraiswamy, S.Liung, V.Dartois, M.Schreiber, S.Hasan, M.Cynamon, N.S.Ryder, X.Yang, B.Weidmann, K.Bracken, T.Dick, and K.Mukherjee (2006).
Peptide deformylase inhibitors as potent antimycobacterial agents.
  Antimicrob Agents Chemother, 50, 3665-3673.  
16144495 D.Chen, and Z.Yuan (2005).
Therapeutic potential of peptide deformylase inhibitors.
  Expert Opin Investig Drugs, 14, 1107-1116.  
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
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
  15489958 M.D.Lee, Y.She, M.J.Soskis, C.P.Borella, J.R.Gardner, P.A.Hayes, B.M.Dy, M.L.Heaney, M.R.Philips, W.G.Bornmann, F.M.Sirotnak, and D.A.Scheinberg (2004).
Human mitochondrial peptide deformylase, a new anticancer target of actinonin-based antibiotics.
  J Clin Invest, 114, 1107-1116.  
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.  
12538898 K.J.Smith, C.M.Petit, K.Aubart, M.Smyth, E.McManus, J.Jones, A.Fosberry, C.Lewis, M.Lonetto, and S.B.Christensen (2003).
Structural variation and inhibitor binding in polypeptide deformylase from four different bacterial species.
  Protein Sci, 12, 349-360.
PDB codes: 2ai7 2ai8 2ai9 2aia 2aie
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.  
12070337 D.W.Byerly, C.A.McElroy, and M.P.Foster (2002).
Mapping the surface of Escherichia coli peptide deformylase by NMR with organic solvents.
  Protein Sci, 11, 1850-1853.  
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
11839307 J.W.Arndt, B.Hao, V.Ramakrishnan, T.Cheng, S.I.Chan, and M.K.Chan (2002).
Crystal structure of a novel carboxypeptidase from the hyperthermophilic archaeon Pyrococcus furiosus.
  Structure, 10, 215-224.
PDB codes: 1k9x 1ka2 1ka4
11976499 Y.Li, S.Ren, and W.Gong (2002).
Cloning, high-level expression, purification and crystallization of peptide deformylase from Leptospira interrogans.
  Acta Crystallogr D Biol Crystallogr, 58, 846-848.  
15992167 C.Giglione, and T.Meinnel (2001).
Peptide deformylase as an emerging target for antiparasitic agents.
  Expert Opin Ther Targets, 5, 41-57.  
11728875 D.McDevitt, and M.Rosenberg (2001).
Exploiting genomics to discover new antibiotics.
  Trends Microbiol, 9, 611-617.  
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
11553770 M.T.Hilgers, and M.L.Ludwig (2001).
Crystal structure of the quorum-sensing protein LuxS reveals a catalytic metal site.
  Proc Natl Acad Sci U S A, 98, 11169-11174.
PDB code: 1ie0
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.  
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.  
10200158 B.Hao, W.Gong, P.T.Rajagopalan, Y.Zhou, D.Pei, and M.K.Chan (1999).
Structural basis for the design of antibiotics targeting peptide deformylase.
  Biochemistry, 38, 4712-4719.
PDB codes: 1bsj 1bsk
  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.  
10226043 M.J.Maroney (1999).
Structure/function relationships in nickel metallobiochemistry.
  Curr Opin Chem Biol, 3, 188-199.  
10194346 T.Meinnel, L.Patiny, S.Ragusa, and S.Blanquet (1999).
Design and synthesis of substrate analogue inhibitors of peptide deformylase.
  Biochemistry, 38, 4287-4295.  
9888804 Y.J.Hu, Y.Wei, Y.Zhou, P.T.Rajagopalan, and D.Pei (1999).
Determination of substrate specificity for peptide deformylase through the screening of a combinatorial peptide library.
  Biochemistry, 38, 643-650.  
9846875 A.Becker, I.Schlichting, W.Kabsch, D.Groche, S.Schultz, and A.F.Wagner (1998).
Iron center, substrate recognition and mechanism of peptide deformylase.
  Nat Struct Biol, 5, 1053-1058.
PDB codes: 1bs4 1bs5 1bs6 1bs8 1bsz
9565550 A.Becker, I.Schlichting, W.Kabsch, S.Schultz, and A.F.Wagner (1998).
Structure of peptide deformylase and identification of the substrate binding site.
  J Biol Chem, 273, 11413-11416.
PDB codes: 1bs7 1icj
9712848 P.T.Rajagopalan, and D.Pei (1998).
Oxygen-mediated inactivation of peptide deformylase.
  J Biol Chem, 273, 22305-22310.  
9671518 T.L.Born, R.Zheng, and J.S.Blanchard (1998).
Hydrolysis of N-succinyl-L,L-diaminopimelic acid by the Haemophilus influenzae dapE-encoded desuccinylase: metal activation, solvent isotope effects, and kinetic mechanism.
  Biochemistry, 37, 10478-10487.  
9873565 Y.J.Hu, P.T.Rajagopalan, and D.Pei (1998).
H-phosphonate derivatives as novel peptide deformylase inhibitors.
  Bioorg Med Chem Lett, 8, 2479-2482.  
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.

 

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