4N95

E. coli sliding clamp in complex with 5-chloroindoline-2,3-dione


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.224 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.188 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Discovery of lead compounds targeting the bacterial sliding clamp using a fragment-based approach.

Yin, Z.Whittell, L.R.Wang, Y.Jergic, S.Liu, M.Harry, E.J.Dixon, N.E.Beck, J.L.Kelso, M.J.Oakley, A.J.

(2014) J Med Chem 57: 2799-2806

  • DOI: https://doi.org/10.1021/jm500122r
  • Primary Citation of Related Structures:  
    4N94, 4N95, 4N96, 4N97, 4N98, 4N99, 4N9A

  • PubMed Abstract: 

    The bacterial sliding clamp (SC), also known as the DNA polymerase III β subunit, is an emerging antibacterial target that plays a central role in DNA replication, serving as a protein-protein interaction hub with a common binding pocket to recognize linear motifs in the partner proteins. Here, fragment-based screening using X-ray crystallography produced four hits bound in the linear-motif-binding pocket of the Escherichia coli SC. Compounds structurally related to the hits were identified that inhibited the E. coli SC and SC-mediated DNA replication in vitro. A tetrahydrocarbazole derivative emerged as a promising lead whose methyl and ethyl ester prodrug forms showed minimum inhibitory concentrations in the range of 21-43 μg/mL against representative Gram-negative and Gram-positive bacteria species. The work demonstrates the utility of a fragment-based approach for identifying bacterial sliding clamp inhibitors as lead compounds with broad-spectrum antibacterial activity.


  • Organizational Affiliation

    School of Chemistry and Centre for Medical and Molecular Bioscience, University of Wollongong , Wollongong, New South Wales 2522, Australia.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DNA polymerase III subunit betaA [auth B],
B [auth A]
366Escherichia coli K-12Mutation(s): 0 
Gene Names: b3701dnaNJW3678
EC: 2.7.7.7
UniProt
Find proteins for P0A988 (Escherichia coli (strain K12))
Explore P0A988 
Go to UniProtKB:  P0A988
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0A988
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 6 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PG4
Query on PG4

Download Ideal Coordinates CCD File 
C [auth B],
D [auth B]
TETRAETHYLENE GLYCOL
C8 H18 O5
UWHCKJMYHZGTIT-UHFFFAOYSA-N
2HQ
Query on 2HQ

Download Ideal Coordinates CCD File 
G [auth A]5-chloro-1H-indole-2,3-dione
C8 H4 Cl N O2
XHDJYQWGFIBCEP-UHFFFAOYSA-N
PGE
Query on PGE

Download Ideal Coordinates CCD File 
L [auth A]TRIETHYLENE GLYCOL
C6 H14 O4
ZIBGPFATKBEMQZ-UHFFFAOYSA-N
PEG
Query on PEG

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E [auth B],
F [auth B],
H [auth A],
I [auth A],
J [auth A]
DI(HYDROXYETHYL)ETHER
C4 H10 O3
MTHSVFCYNBDYFN-UHFFFAOYSA-N
CA
Query on CA

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M [auth A],
N [auth A],
O [auth A],
P [auth A]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
K [auth A]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.224 
  • R-Value Work: 0.186 
  • R-Value Observed: 0.188 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 40.72α = 73.88
b = 64.04β = 82.29
c = 71.7γ = 84.03
Software Package:
Software NamePurpose
SCALAdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
ADSCdata collection
MOSFLMdata reduction
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-11-06
    Type: Initial release
  • Version 1.1: 2014-04-02
    Changes: Database references
  • Version 1.2: 2014-04-09
    Changes: Database references
  • Version 1.3: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description