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 Smith, K. J. Articles by Christensen, S. B. Search for Related Content PubMed PubMed Citation Articles by Smith, K. J. Articles by Christensen, S. B. Social Bookmarking                   What's this?

Structural variation and inhibitor binding in polypeptide deformylase from four different bacterial species

¹ GlaxoSmithKline, Harlow, Essex CM19 5AW, UK
² GlaxoSmithKline, King of Prussia, Pennsylvania 19406, USA
³ Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK

Reprint requests to: Kathrine J. Smith, GlaxoSmithKline, NFSP (N), Structural Biology Group, CASS, Third Avenue, Harlow, Essex CM19 5AW, UK; e-mail: Kathrine_J_Smith{at}gsk.com; fax: 44 (0) 1279 627896.

Polypeptide deformylase (PDF) catalyzes the deformylation of polypeptide chains in bacteria. It is essential for bacterial cell viability and is a potential antibacterial drug target. Here, we report the crystal structures of polypeptide deformylase from four different species of bacteria: Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Escherichia coli. Comparison of these four structures reveals significant overall differences between the two Gram-negative species (E. coli and H. influenzae) and the two Gram-positive species (S. pneumoniae and S. aureus). Despite these differences and low overall sequence identity, the S1' pocket of PDF is well conserved among the four enzymes studied. We also describe the binding of nonpeptidic inhibitor molecules SB-485345, SB-543668, and SB-505684 to both S. pneumoniae and E. coli PDF. Comparison of these structures shows similar binding interactions with both Gram-negative and Gram-positive species. Understanding the similarities and subtle differences in active site structure between species will help to design broad-spectrum polypeptide deformylase inhibitor molecules.

Keywords: PDF; deformylase; crystal structure; Escherichia coli; Haemophilus influenzae; Staphylococcus aureus; Streptococcus pneumoniae

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				R. Saxena, P. Kanudia, M. Datt, H. H. Dar, S. Karthikeyan, B. Singh, and P. K. Chakraborti Three Consecutive Arginines Are Important for the Mycobacterial Peptide Deformylase Enzyme Activity J. Biol. Chem., August 29, 2008; 283(35): 23754 - 23764. [Abstract] [Full Text] [PDF]

				J. Huang, G. S. Van Aller, A. N. Taylor, J. J. Kerrigan, W.-S. Liu, J. M. Trulli, Z. Lai, D. Holmes, K. M. Aubart, J. R. Brown, et al. Phylogenomic and Biochemical Characterization of Three Legionella pneumophila Polypeptide Deformylases. J. Bacteriol., July 1, 2006; 188(14): 5249 - 5257. [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]

				I. T. Kudva, R. W. Griffin, J. M. Garren, S. B. Calderwood, and M. John Identification of a Protein Subset of the Anthrax Spore Immunome in Humans Immunized with the Anthrax Vaccine Adsorbed Preparation Infect. Immun., September 1, 2005; 73(9): 5685 - 5696. [Abstract] [Full Text] [PDF]