3u7n

Crystal structures of the Staphylococcus aureus peptide deformylase in complex with two classes of new inhibitors

spinqualitylabelsall models 3u7n, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3u7n is a 1 chain structure with sequence from Staphylococcus aureus subsp. aureus COL. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Ligands: CSD, UHF, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DEF_STAAC Removes the formyl group from the N-terminal Met of newly synthesized proteins. Requires at least a dipeptide for an efficient rate of reaction. N-terminal L-methionine is a prerequisite for activity but the enzyme has broad specificity at other positions.[HAMAP-Rule:MF_00163] Publication Abstract from PubMed Peptide deformylase (PDF) catalyzes the removal of the formyl group from the N-terminal methionine residue in newly synthesized polypeptides, which is an essential process in bacteria. Four new inhibitors of PDF that belong to two different classes, hydroxamate/pseudopeptide compounds [PMT387 (7a) and PMT497] and reverse-hydroxamate/nonpeptide compounds [PMT1039 (15e) and PMT1067], have been developed. These compounds inhibited the growth of several pathogens involved in respiratory-tract infections, such as Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae, and leading nosocomial pathogens such as Staphylococcus aureus and Klebsiella pneumoniae with a minimum inhibitory concentration (MIC) in the range 0.1-0.8 mg ml(-1). Interestingly, the reverse-hydroxamate/nonpeptide compounds showed a 250-fold higher antimicrobial activity towards S. aureus, although the four compounds showed similar K(i) values against S. aureus PDF enzymes, with K(i) values in the 11-85 nM range. To provide a structural basis for the discovery of additional PDF inhibitors, the crystal structures of S. aureus PDF in complex with the four inhibitors were determined at resolutions of 1.90-2.30 A. The inhibitor-bound structures displayed distinct deviations depending on the inhibitor class. The distance between the Zn(2+) ion and the carbonyl O atom of the hydroxamate inhibitors (or the hydroxyl O atom of the reverse-hydroxamate inhibitors) appears to be correlated to S. aureus inhibition activity. The structural information reported in this study should aid in the discovery of new PDF inhibitors that can be used as novel antibacterial drugs. Structures of Staphylococcus aureus peptide deformylase in complex with two classes of new inhibitors.,Lee SJ, Lee SJ, Lee SK, Yoon HJ, Lee HH, Kim KK, Lee BJ, Lee BI, Suh SW Acta Crystallogr D Biol Crystallogr. 2012 Jul;68(Pt 7):784-93. doi:, 10.1107/S0907444912011912. Epub 2012 Jun 15. PMID:22751663 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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