3PHE

HCV NS5B with a bound quinolone inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.223 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Quinolones as HCV NS5B polymerase inhibitors.

Kumar, D.V.Rai, R.Brameld, K.A.Somoza, J.R.Rajagopalan, R.Janc, J.W.Xia, Y.M.Ton, T.L.Shaghafi, M.B.Hu, H.Lehoux, I.To, N.Young, W.B.Green, M.J.

(2011) Bioorg Med Chem Lett 21: 82-87

  • DOI: https://doi.org/10.1016/j.bmcl.2010.11.068
  • Primary Citation of Related Structures:  
    3PHE, 3UDL

  • PubMed Abstract: 

    Hepatitis C virus (HCV) infection is treated with a combination of peginterferon alfa-2a/b and ribavirin. To address the limitations of this therapy, numerous small molecule agents are in development, which act by directly affecting key steps in the viral life-cycle. Herein we describe our discovery of quinolone derivatives, novel small-molecules that inhibit NS5b polymerase, a key enzyme of the viral life-cycle. A crystal structure of a quinoline analog bound to NS5B reveals that this class of compounds binds to allosteric site-II (non-nucleoside inhibitor-site 2, NNI-2) of this protein.


  • Organizational Affiliation

    Myriad Pharmaceuticals, 305 Chipeta Way, Salt Lake City, UT 84108, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HCV encoded nonstructural 5B protein
A, B, C, D
576Hepacivirus hominisMutation(s): 0 
UniProt
Find proteins for D0PY27 (Hepacivirus hominis)
Explore D0PY27 
Go to UniProtKB:  D0PY27
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupD0PY27
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
C9A PDBBind:  3PHE IC50: 16 (nM) from 1 assay(s)
Binding MOAD:  3PHE IC50: 16 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.223 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 101.751α = 90
b = 101.972β = 90
c = 251.087γ = 90
Software Package:
Software NamePurpose
BOSdata collection
EPMRphasing
CNXrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-11-17
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2024-02-21
    Changes: Data collection, Database references, Derived calculations