2QE2

Structure of HCV NS5B Bound to an Anthranilic Acid Inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.296 
  • R-Value Work: 0.279 
  • R-Value Observed: 0.279 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Identification of Anthranilic Acid Derivatives as a Novel Class of Allosteric Inhibitors of Hepatitis C NS5B Polymerase

Nittoli, T.Curran, K.Insaf, S.DiGrandi, M.Orlowski, M.Chopra, R.Agarwal, A.Howe, A.Y.M.Prashad, A.Brawner Floyd, M.Johnson, B.Sutherland, A.Wheless, K.Feld, B.O'Connell, J.Mansour, T.S.Bloom, J.

(2007) J Med Chem 50: 2108-2116

  • DOI: https://doi.org/10.1021/jm061428x
  • Primary Citation of Related Structures:  
    2QE2, 2QE5

  • PubMed Abstract: 

    A series of potent anthranilic acid-based inhibitors of the hepatitis C NS5B polymerase has been identified. The inhibitors bind to a site on NS5B between the thumb and palm regions adjacent to the active site as determined by X-ray crystallography of the enzyme-inhibitor complex. Guided by both molecular modeling and traditional SAR, the enzyme activity of the initial hit was improved by approximately 100-fold, yielding a series of potent and selective NS5B inhibitors with IC50 values as low as 10 nM. These compounds were also inhibitors of the HCV replicon in cultured HUH7 cells.


  • Organizational Affiliation

    Chemical and Screening Sciences and Infectious Diseases Research, Wyeth Research, 401 N. Middletown Road, Pearl River, New York 10965, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
RNA-directed RNA polymerase
A, B
578Hepatitis C virus subtype 1bMutation(s): 0 
Gene Names: ns5b
EC: 2.7.7.48
UniProt
Find proteins for Q99AU2 (Hepatitis C virus subtype 1b)
Explore Q99AU2 
Go to UniProtKB:  Q99AU2
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ99AU2
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
452
Query on 452

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
2-{[N-(2-ACETYL-5-CHLORO-4-FLUOROPHENYL)GLYCYL]AMINO}BENZOIC ACID
C17 H14 Cl F N2 O4
LBMZLHCAPBBOFS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
452 PDBBind:  2QE2 IC50: 17 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.296 
  • R-Value Work: 0.279 
  • R-Value Observed: 0.279 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 70.835α = 90
b = 70.878β = 90
c = 251.653γ = 90
Software Package:
Software NamePurpose
CNSrefinement
ADSCdata collection
HKL-2000data reduction
HKL-2000data scaling
AMoREphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-10-02
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-08-30
    Changes: Data collection, Database references, Refinement description