4OVG

E. coli sliding clamp in complex with (R)-9-(2-amino-2-oxoethyl)-6-chloro-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylic acid


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.183 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Bacterial Sliding Clamp Inhibitors that Mimic the Sequential Binding Mechanism of Endogenous Linear Motifs.

Yin, Z.Whittell, L.R.Wang, Y.Jergic, S.Ma, C.Lewis, P.J.Dixon, N.E.Beck, J.L.Kelso, M.J.Oakley, A.J.

(2015) J Med Chem 58: 4693-4702

  • DOI: https://doi.org/10.1021/acs.jmedchem.5b00232
  • Primary Citation of Related Structures:  
    4OVF, 4OVG, 4OVH, 4PNU, 4PNV, 4PNW

  • PubMed Abstract: 

    The bacterial DNA replication machinery presents new targets for the development of antibiotics acting via novel mechanisms. One such target is the protein-protein interaction between the DNA sliding clamp and the conserved peptide linear motifs in DNA polymerases. We previously established that binding of linear motifs to the Escherichia coli sliding clamp occurs via a sequential mechanism that involves two subsites (I and II). Here, we report the development of small-molecule inhibitors that mimic this mechanism. The compounds contain tetrahydrocarbazole moieties as "anchors" to occupy subsite I. Functional groups appended at the tetrahydrocarbazole nitrogen bind to a channel gated by the side chain of M362 and lie at the edge of subsite II. One derivative induced the formation of a new binding pocket, termed subsite III, by rearrangement of a loop adjacent to subsite I. Discovery of the extended binding area will guide further inhibitor development.


  • Organizational Affiliation

    †School of Chemistry and Centre for Medical and Molecular Bioscience, The University of Wollongong and The Illawarra Health and Medical Research Institute, 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 beta
A, B
366Escherichia coli str. K-12 substr. MC4100Mutation(s): 0 
Gene Names: BN896_3391dnaN
EC: 2.7.7.7
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 7 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
2VF
Query on 2VF

Download Ideal Coordinates CCD File 
C [auth A],
M [auth B]
(2R)-9-(2-amino-2-oxoethyl)-6-chloro-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylic acid
C15 H15 Cl N2 O3
WEITVQPGVPEPAZ-MRVPVSSYSA-N
PG4
Query on PG4

Download Ideal Coordinates CCD File 
G [auth A],
P [auth B]
TETRAETHYLENE GLYCOL
C8 H18 O5
UWHCKJMYHZGTIT-UHFFFAOYSA-N
PGE
Query on PGE

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

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A],
N [auth B],
O [auth B]
DI(HYDROXYETHYL)ETHER
C4 H10 O3
MTHSVFCYNBDYFN-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
K [auth A]1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
F [auth A],
H [auth A],
I [auth A],
J [auth A]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
L [auth A],
R [auth B]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Binding Affinity Annotations 
IDSourceBinding Affinity
2VF BindingDB:  4OVG Ki: 2.04e+5 (nM) from 1 assay(s)
IC50: 3.68e+5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.183 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 80.079α = 90
b = 66.197β = 114.9
c = 80.625γ = 90
Software Package:
Software NamePurpose
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
MAR345dtbdata collection
HKL-2000data reduction
MOLREPphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-03-05
    Type: Initial release
  • Version 1.1: 2015-06-24
    Changes: Database references
  • Version 1.2: 2024-02-28
    Changes: Data collection, Database references, Derived calculations