5TRJ

CRYSTAL STRUCTURE OF THE HEPATITIS C VIRUS NS5B RNA-DEPENDENT RNA POLYMERASE IN COMPLEX WITH 2-{[2-(carboxymethoxy)benzene-1-carbonyl]amino}-3-[(4-chlorophenyl)methoxy]benzoic acid

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.57 Å
  • R-Value Free: 0.236 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.206 

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Ligand Structure Quality Assessment 


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


Literature

Discovery and initial optimization of alkoxyanthranilic acid derivatives as inhibitors of HCV NS5B polymerase.

Parcella, K., Nickel, A., Beno, B.R., Sheriff, S., Wan, C., Wang, Y.K., Roberts, S.B., Meanwell, N.A., Kadow, J.F.

(2017) Bioorg Med Chem Lett 27: 295-298

  • DOI: https://doi.org/10.1016/j.bmcl.2016.11.054
  • Primary Citation of Related Structures:  
    5TRH, 5TRI, 5TRJ, 5TRK

  • PubMed Abstract: 

    Alkoxyanthranilic acid derivatives have been identified to inhibit HCV NS5B polymerase, binding in an allosteric site located at the convergence of the palm and thumb regions. Information from co-crystal structures guided the structural design strategy. Ultimately, two independent structural modifications led to a similar shift in binding mode that when combined led to a synergistic improvement in potency and the identification of inhibitors with sub-micromolar HCV NS5B binding potency.

    • Organizational Affiliation: 

    Bristol-Myers Squibb, Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA. Electronic address: kyle.parcella@bms.com.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
RNA-DEPENDENT RNA POLYMERASE
A, B
574Hepacivirus hominisMutation(s): 0 
EC: 2.7.7.48
UniProt
Find proteins for Q9WMX2 (Hepatitis C virus genotype 1b (isolate Con1))
Explore Q9WMX2 
Go to UniProtKB:  Q9WMX2
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9WMX2
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
23E
Query on 23E
Download Ideal Coordinates CCD File 
C [auth A],
J [auth B]		(2E)-3-(4-{[(1-{[(13-cyclohexyl-6-oxo-6,7-dihydro-5H-indolo[1,2-d][1,4]benzodiazepin-10-yl)carbonyl]amino}cyclopentyl)carbonyl]amino}phenyl)prop-2-enoic acid
C38 H38 N4 O5
HDBNVTWMHMMKNY-XMHGGMMESA-N
7HO
Query on 7HO
Download Ideal Coordinates CCD File 
D [auth A],
K [auth B]		2-{[2-(carboxymethoxy)benzene-1-carbonyl]amino}-3-[(4-chlorophenyl)methoxy]benzoic acid
C23 H18 Cl N O7
UUTYKXCXDYRGKN-UHFFFAOYSA-N
SO4
Query on SO4
Download Ideal Coordinates CCD File 
E [auth A]
F [auth A]
G [auth A]
H [auth A]
I [auth A]
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
L [auth B],
M [auth B],
N [auth B],
O [auth B],
P [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.57 Å
  • R-Value Free: 0.236 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.206 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 66.4α = 90
b = 91.5β = 90
c = 232.8γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction
HKL-2000data scaling
AMoREphasing

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

  • Released Date: 2016-11-30 
    • Deposition Author(s): Sheriff, S.

Revision History  (Full details and data files)

  • Version 1.0: 2016-11-30
    Type: Initial release
  • Version 1.1: 2016-12-21
    Changes: Database references
  • Version 1.2: 2017-01-11
    Changes: Database references
  • Version 1.3: 2023-10-04
    Changes: Data collection, Database references, Refinement description