2HWI

HCV NS5B allosteric inhibitor complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.223 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structure-based design of a novel thiazolone scaffold as HCV NS5B polymerase allosteric inhibitors.

Yan, S.Appleby, T.Larson, G.Wu, J.Z.Hamatake, R.Hong, Z.Yao, N.

(2006) Bioorg Med Chem Lett 16: 5888-5891

  • DOI: https://doi.org/10.1016/j.bmcl.2006.08.056
  • Primary Citation of Related Structures:  
    2HWH, 2HWI

  • PubMed Abstract: 

    A structure-based approach was performed to design a novel thiazolone scaffold as HCV NS5B inhibitors. A focused library was designed and docked by GOLD. One of the top-scored molecules was synthesized and shown to have similar potency to the initial hit. The X-ray complex structure was determined and validated our design rationale.


  • Organizational Affiliation

    Valeant Pharmaceuticals Research and Development, 3300 Hyland Ave. Costa Mesa, CA 92626, USA. syan@valeant.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
RNA-directed RNA polymerase (NS5B) (p68)
A, B
576Hepacivirus hominisMutation(s): 0 
EC: 2.7.7.48
UniProt
Find proteins for P26663 (Hepatitis C virus genotype 1b (isolate BK))
Explore P26663 
Go to UniProtKB:  P26663
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP26663
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
VRX
Query on VRX

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
(2S)-({(5Z)-5-[(5-ETHYL-2-FURYL)METHYLENE]-4-OXO-4,5-DIHYDRO-1,3-THIAZOL-2-YL}AMINO)(4-FLUOROPHENYL)ACETIC ACID
C18 H15 F N2 O4 S
RNEACARJKXYVND-MZLJFPOFSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
VRX Binding MOAD:  2HWI IC50: 3000 (nM) from 1 assay(s)
PDBBind:  2HWI IC50: 3000 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.223 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 84.997α = 90
b = 106.585β = 90
c = 127.2γ = 90
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata reduction
HKL-2000data scaling
CNSphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2006-11-07 
  • Deposition Author(s): Yao, N.

Revision History  (Full details and data files)

  • Version 1.0: 2006-11-07
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description