PDBsum entry 1bs7

Hydrolase

PDB id

1bs7

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Contents

			Protein chains

					168 a.a. *

			Ligands

					SO4 ×2

			Metals

					_NI ×3

			Waters ×131

* Residue conservation analysis

PDB id:

1bs7

Links

Name:

Hydrolase

Title:

Peptide deformylase as ni2+ containing form

Structure:

Protein (peptide deformylase). Chain: a, b, c. Synonym: pdf. Engineered: yes. Other_details: pdf protein from escherichia coli is crystallized as ni2+ containing form

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)

Resolution:

2.50Å

R-factor:

0.203

R-free:

0.272

Authors:

A.Becker,I.Schlichting,W.Kabsch,D.Groche,S.Schultz,A.F.V.Wagner

Key ref:

A.Becker et al. (1998). Structure of peptide deformylase and identification of the substrate binding site. J Biol Chem, 273, 11413-11416. PubMed id: 9565550 DOI: 10.1074/jbc.273.19.11413

Date:

01-Sep-98

Release date:

27-Aug-99

PROCHECK

	Headers

	References

Protein chains

P0A6K3 (DEF_ECOLI) - Peptide deformylase from Escherichia coli (strain K12)

Seq: Struc:					169 a.a. 168 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: 10.1074/jbc.273.19.11413	J Biol Chem 273:11413-11416 (1998)
PubMed id: 9565550

Structure of peptide deformylase and identification of the substrate binding site.
A.Becker, I.Schlichting, W.Kabsch, S.Schultz, A.F.Wagner.

ABSTRACT

Peptide deformylase is an essential metalloenzyme required for the removal of the formyl group at the N terminus of nascent polypeptide chains in eubacteria. The Escherichia coli enzyme uses Fe2+ and nearly retains its activity on substitution of the metal ion by Ni2+. We have solved the structure of the Ni2+ enzyme at 1.9-A resolution by x-ray crystallography. Each of the three monomers in the asymmetric unit contains one Ni2+ ion and, in close proximity, one molecule of polyethylene glycol. Polyethylene glycol is shown to be a competitive inhibitor with a KI value of 6 mM with respect to formylmethionine under conditions similar to those used for crystallization. We have also solved the structure of the inhibitor-free enzyme at 2.5-A resolution. The two structures are identical within the estimated errors of the models. The hydrogen bond network stabilizing the active site involves nearly all conserved amino acid residues and well defined water molecules, one of which ligates to the tetrahedrally coordinated Ni2+ ion.

Selected figure(s)



	Figure 2. Fig. 2. Schematic representation of secondary structure as analyzed by the program DSSP (14). First and last amino acid residues in the helices and sheet strands are specified.		Figure 5. Fig. 5. Interaction scheme between the catalytic Ni2+ ion, water molecules W1, W2, W3, and amino acid residues in the active site of peptide deformylase. With the exception of Leu-6, all residues shown in the figure are well conserved. Bonds and bond angles between the Ni2+ ion and its ligands are shown. Dashed lines indicate hydrogen bonds with distances between donor and acceptor atom given in Å. The second proton of W1 and the distance to the side chain of Gln-50 are in brackets to indicate the absence of a hydrogen bond.

Figures were selected by the author.

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.

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

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.

16342948

A.L.McClerren, S.Endsley, J.L.Bowman, N.H.Andersen, Z.Guan, J.Rudolph, and C.R.Raetz (2005).
A slow, tight-binding inhibitor of the zinc-dependent deacetylase LpxC of lipid A biosynthesis with antibiotic activity comparable to ciprofloxacin.

Biochemistry, 44, 16574-16583.

15937276

S.W.Aufhammer, E.Warkentin, U.Ermler, C.H.Hagemeier, R.K.Thauer, and S.Shima (2005).
Crystal structure of methylenetetrahydromethanopterin reductase (Mer) in complex with coenzyme F420: Architecture of the F420/FMN binding site of enzymes within the nonprolyl cis-peptide containing bacterial luciferase family.

Protein Sci, 14, 1840-1849.

PDB code:

1z69

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

12829270

S.B.Mulrooney, and R.P.Hausinger (2003).
Nickel uptake and utilization by microorganisms.

FEMS Microbiol Rev, 27, 239-261.

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.

11754252

P.A.Wabnitz, and J.A.Loo (2002).
Drug screening of pharmaceutical discovery compounds by micro-size exclusion chromatography/mass spectrometry.

Rapid Commun Mass Spectrom, 16, 85-91.

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

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.

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.

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

10226043

M.J.Maroney (1999).
Structure/function relationships in nickel metallobiochemistry.

Curr Opin Chem Biol, 3, 188-199.

10647182

P.Gouet, B.Fabry, V.Guillet, C.Birck, L.Mourey, D.Kahn, and J.P.Samama (1999).
Structural transitions in the FixJ receiver domain.

Structure, 7, 1517-1526.

PDB codes:

1dbw 1dck 1dcm

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

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.