HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Becker, A. Articles by Wagner, A. F. V. Search for Related Content PubMed PubMed Citation Articles by Becker, A. Articles by Wagner, A. F. V. Social Bookmarking                      What's this?

J Biol Chem, Vol. 273, Issue 19, 11413-11416, May 8, 1998

COMMUNICATION
Structure of Peptide Deformylase and Identification of the Substrate Binding Site

Andreas Becker, Ilme Schlichting^§, Wolfgang Kabsch, Sabine Schultz, and A. F. Volker Wagner

From the  Max-Planck-Institut für medizinische Forschung, Abteilung Biophysik, Jahnstrasse 29, 69120 Heidelberg, Germany, ^§ Max-Planck-Institut für molekulare Physiologie, Abteilung Physikalische Biochemie, Rheinlanddamm 201, 44139 Dortmund, Germany, and  Biochemie-Zentrum Heidelberg, Ruprecht-Karls Universität, Im Neuenheimer Feld 501, 69120 Heidelberg, Germany

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-Å 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 K_I 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-Å 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.

---

Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				S. Ravaud, G. Stjepanovic, K. Wild, and I. Sinning The Crystal Structure of the Periplasmic Domain of the Escherichia coli Membrane Protein Insertase YidC Contains a Substrate Binding Cleft J. Biol. Chem., April 4, 2008; 283(14): 9350 - 9358. [Abstract] [Full Text] [PDF]

				A. A. Watters, R. N. Jones, J. A. Leeds, G. Denys, H. S. Sader, and T. R. Fritsche Antimicrobial activity of a novel peptide deformylase inhibitor, LBM415, tested against respiratory tract and cutaneous infection pathogens: a global surveillance report (2003-2004) J. Antimicrob. Chemother., May 1, 2006; 57(5): 914 - 923. [Abstract] [Full Text] [PDF]

				S. Fieulaine, C. Juillan-Binard, A. Serero, F. Dardel, C. Giglione, T. Meinnel, and J.-L. Ferrer 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., December 23, 2005; 280(51): 42315 - 42324. [Abstract] [Full Text] [PDF]

				S. W. Aufhammer, E. Warkentin, U. Ermler, C. H. Hagemeier, R. K. Thauer, and S. Shima 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., July 1, 2005; 14(7): 1840 - 1849. [Abstract] [Full Text] [PDF]

				O. Pylypenko, F. Vitali, K. Zerbe, J. A. Robinson, and I. Schlichting Crystal Structure of OxyC, a Cytochrome P450 Implicated in an Oxidative C-C Coupling Reaction during Vancomycin Biosynthesis J. Biol. Chem., November 21, 2003; 278(47): 46727 - 46733. [Abstract] [Full Text] [PDF]

				K. J. Smith, C. M. Petit, K. Aubart, M. Smyth, E. McManus, J. Jones, A. Fosberry, C. Lewis, M. Lonetto, and S. B. Christensen Structural variation and inhibitor binding in polypeptide deformylase from four different bacterial species Protein Sci., February 1, 2003; 12(2): 349 - 360. [Abstract] [Full Text] [PDF]

				S. Sheng, C. J. Perry, and T. R. Kleyman External Nickel Inhibits Epithelial Sodium Channel by Binding to Histidine Residues within the Extracellular Domains of alpha and gamma Subunits and Reducing Channel Open Probability J. Biol. Chem., December 13, 2002; 277(51): 50098 - 50111. [Abstract] [Full Text] [PDF]

				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, et al. N-Alkyl Urea Hydroxamic Acids as a New Class of Peptide Deformylase Inhibitors with Antibacterial Activity Antimicrob. Agents Chemother., September 1, 2002; 46(9): 2752 - 2764. [Abstract] [Full Text] [PDF]

				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, et al. Crystal Structure of Type II Peptide Deformylase from Staphylococcus aureus J. Biol. Chem., August 16, 2002; 277(34): 31163 - 31171. [Abstract] [Full Text] [PDF]

				D. W. Byerly, C. A. McElroy, and M. P. Foster Mapping the surface of Escherichia coli peptide deformylase by NMR with organic solvents Protein Sci., July 1, 2002; 11(7): 1850 - 1853. [Abstract] [Full Text] [PDF]

				P. Margolis, C. Hackbarth, S. Lopez, M. Maniar, W. Wang, Z. Yuan, R. White, and J. Trias Resistance of Streptococcus pneumoniae to Deformylase Inhibitors Is Due to Mutations in defB Antimicrob. Agents Chemother., September 1, 2001; 45(9): 2432 - 2435. [Abstract] [Full Text] [PDF]

				L. M.A. Dirk, M. A. Williams, and R. L. Houtz Eukaryotic Peptide Deformylases. Nuclear-Encoded and Chloroplast-Targeted Enzymes in Arabidopsis Plant Physiology, September 1, 2001; 127(1): 97 - 107. [Abstract] [Full Text] [PDF]

				J. M. Clements, R. P. Beckett, A. Brown, G. Catlin, M. Lobell, S. Palan, W. Thomas, M. Whittaker, S. Wood, S. Salama, et al. Antibiotic Activity and Characterization of BB-3497, a Novel Peptide Deformylase Inhibitor Antimicrob. Agents Chemother., February 1, 2001; 45(2): 563 - 570. [Abstract] [Full Text]

				P. S. Margolis, C. J. Hackbarth, D. C. Young, W. Wang, D. Chen, Z. Yuan, R. White, and J. Trias Peptide Deformylase in Staphylococcus aureus: Resistance to Inhibition Is Mediated by Mutations in the Formyltransferase Gene Antimicrob. Agents Chemother., July 1, 2000; 44(7): 1825 - 1831. [Abstract] [Full Text]

				P. T. R. Rajagopalan and D. Pei Oxygen-mediated Inactivation of Peptide Deformylase J. Biol. Chem., August 28, 1998; 273(35): 22305 - 22310. [Abstract] [Full Text] [PDF]