PMID:12538898

Citation	Smith, KJ, Petit, CM, Aubart, K, Smyth, M, McManus, E, Jones, J, Fosberry, A, Lewis, C, Lonetto, M and Christensen, SB (2003) Structural variation and inhibitor binding in polypeptide deformylase from four different bacterial species. Protein Sci. 12:349-60
Abstract	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.
Links	PubMed PMC2312423 Online version:10.1110/ps.0229303
Keywords	Amidohydrolases; Amino Acid Sequence; Aminopeptidases/antagonists & inhibitors; Aminopeptidases/chemistry; Aminopeptidases/metabolism; Bacterial Proteins/antagonists & inhibitors; Bacterial Proteins/chemistry; Bacterial Proteins/metabolism; Binding Sites; Crystallography, X-Ray; Enzyme Inhibitors/chemistry; Enzyme Inhibitors/metabolism; Enzyme Inhibitors/pharmacology; Escherichia coli/drug effects; Escherichia coli/enzymology; Haemophilus influenzae/drug effects; Haemophilus influenzae/enzymology; Kinetics; Microbial Sensitivity Tests; Models, Molecular; Molecular Sequence Data; Peptides; Protein Binding; Protein Conformation; Sequence Homology, Amino Acid; Staphylococcus aureus/drug effects; Staphylococcus aureus/enzymology; Streptococcus pneumoniae/drug effects; Streptococcus pneumoniae/enzymology
edit table

Significance

You can help EcoliWiki by summarizing why this paper is useful

Useful Materials and Methods

You can help Ecoliwiki by describing the useful materials (strains, plasmids, antibodies, etc) described in this paper.

Annotations

<annotationlinks/>

EcoliWiki Links

Add links to pages that link here (e.g. gene, product, method pages)

References

See Help:References for how to manage references in EcoliWiki.