1S17

Identification of Novel Potent Bicyclic Peptide Deformylase Inhibitors

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.196 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history. 


Literature

Identification of novel potent bicyclic peptide deformylase inhibitors

Molteni, V., He, X., Nabakka, J., Yang, K., Kreusch, A., Gordon, P., Bursulaya, B., Warner, I., Shin, T., Biorac, T., Ryder, N.S., Goldberg, R., Doughty, J., He, Y.

(2004) Bioorg Med Chem Lett 14: 1477-1481

  • DOI: https://doi.org/10.1016/j.bmcl.2004.01.014
  • Primary Citation of Related Structures:  
    1S17

  • PubMed Abstract: 

    Screening of our compound collection using Staphylococcus aureus Ni-Peptide deformylase (PDF) afforded a very potent PDF inhibitor with an IC(50) in the low nanomolar range but with poor antibacterial activity (MIC). Three-dimensional structural information obtained from Pseudomonas aeruginosa Ni-PDF complexed with the inhibitor suggested the synthesis of a variety of analogues that would maintain high binding affinity while attempting to improve antibacterial activity. Many of the compounds synthesized proved to be excellent PDF-Ni inhibitors and some showed increased antibacterial activity in selected strains.

    • Organizational Affiliation: 

    Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA. vmolteni@gnf.org


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Peptide deformylase
A, B
180Pseudomonas aeruginosaMutation(s): 0 
Gene Names: DEF, PA0019
EC: 3.5.1.88
UniProt
Find proteins for Q9I7A8 (Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1))
Explore Q9I7A8 
Go to UniProtKB:  Q9I7A8
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9I7A8
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
GNR
Query on GNR
Download Ideal Coordinates CCD File 
D [auth A],
G [auth B]		2-(3,4-DIHYDRO-3-OXO-2H-BENZO[B][1,4]THIAZIN-2-YL)-N-HYDROXYACETAMIDE
C10 H10 N2 O3 S
UKDWCJNGBPZOBU-MRVPVSSYSA-N
GOL
Query on GOL
Download Ideal Coordinates CCD File 
E [auth A]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
NI
Query on NI
Download Ideal Coordinates CCD File 
C [auth A],
F [auth B]		NICKEL (II) ION
Ni
VEQPNABPJHWNSG-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
GNR Binding MOAD:  1S17 IC50: 5 (nM) from 1 assay(s)
PDBBind:  1S17 IC50: 5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.196 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 69.009α = 90
b = 73.994β = 90
c = 76.864γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing
CNSrefinement

Structure Validation

View Full Validation Report



View more in-depth experimental data
Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-03-30
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2023-08-23
    Changes: Data collection, Database references, Derived calculations, Refinement description