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

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Smith KJ, Petit CM, Aubart K, Smyth M, McManus E, Jones J, Fosberry A, Lewis C, Lonetto M, Christensen SB

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

Protein Sci. 2003 Feb;12(2):349-60.

PubMed ID
12538898 [ View in PubMed
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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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
2-(3-BENZOYLPHENOXY)ETHYL(HYDROXY)FORMAMIDEPeptide deformylaseIC 50 (nM)39007.625Details
HYDROXY[3-(6-METHYLPYRIDIN-2-YL)PROPYL]FORMAMIDEPeptide deformylaseIC 50 (nM)22007.625Details