3U7N

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.195 

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Literature

Structures of Staphylococcus aureus peptide deformylase in complex with two classes of new inhibitors

Lee, S.J.Lee, S.-J.Lee, S.K.Yoon, H.-J.Lee, H.H.Kim, K.K.Lee, B.J.Lee, B.I.Suh, S.W.

(2012) Acta Crystallogr D Biol Crystallogr 68: 784-793

  • DOI: https://doi.org/10.1107/S0907444912011912
  • Primary Citation of Related Structures:  
    3U7K, 3U7L, 3U7M, 3U7N

  • PubMed Abstract: 

    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 Å. 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.


  • Organizational Affiliation

    Biomolecular Function Research Branch, Division of Convergence Technology, Research Institute, National Cancer Center, Goyang, Gyeonggi 410-749, Republic of Korea.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Peptide deformylase191Staphylococcus aureus subsp. aureus COLMutation(s): 0 
Gene Names: sacol1100
EC: 3.5.1.88
UniProt
Find proteins for Q5HGZ3 (Staphylococcus aureus (strain COL))
Explore Q5HGZ3 
Go to UniProtKB:  Q5HGZ3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ5HGZ3
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
UHF
Query on UHF

Download Ideal Coordinates CCD File 
C [auth A]N-((2R,4S)-2-butyl-5-methyl-4-(3-(5-methylpyridin-2-yl)ureido)-3-oxohexyl)-N-hydroxyformamide
C19 H30 N4 O4
AMPUUHFRILVRDV-WBVHZDCISA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
B [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
CSD
Query on CSD
A
L-PEPTIDE LINKINGC3 H7 N O4 SCYS
Binding Affinity Annotations 
IDSourceBinding Affinity
UHF PDBBind:  3U7N Ki: 11.2 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.195 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 93.747α = 90
b = 120.653β = 90
c = 47.562γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
MOLREPphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-06-27
    Type: Initial release
  • Version 1.1: 2017-03-01
    Changes: Database references
  • Version 1.2: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description