4KAI

HCV NS5B GT1B N316 with GSK5852A


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.198 
  • R-Value Observed: 0.201 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.6 of the entry. See complete history


Literature

Discovery of a Potent Boronic Acid Derived Inhibitor of the HCV RNA-Dependent RNA Polymerase.

Maynard, A.Crosby, R.M.Ellis, B.Hamatake, R.Hong, Z.Johns, B.A.Kahler, K.M.Koble, C.Leivers, A.Leivers, M.R.Mathis, A.Peat, A.J.Pouliot, J.J.Roberts, C.D.Samano, V.Schmidt, R.M.Smith, G.K.Spaltenstein, A.Stewart, E.L.Thommes, P.Turner, E.M.Voitenleitner, C.Walker, J.T.Waitt, G.Weatherhead, J.Weaver, K.Williams, S.Wright, L.Xiong, Z.Z.Haigh, D.Shotwell, J.B.

(2014) J Med Chem 57: 1902-1913

  • DOI: https://doi.org/10.1021/jm400317w
  • Primary Citation of Related Structures:  
    4KAI, 4KB7, 4KBI, 4KE5, 4KHM, 4KHR

  • PubMed Abstract: 

    A boronic acid moiety was found to be a critical pharmacophore for enhanced in vitro potency against wild-type hepatitis C replicons and known clinical polymorphic and resistant HCV mutant replicons. The synthesis, optimization, and structure-activity relationships associated with inhibition of HCV replication in a subgenomic replication system for a series of non-nucleoside boron-containing HCV RNA-dependent RNA polymerase (NS5B) inhibitors are described. A summary of the discovery of 3 (GSK5852), a molecule which entered clinical trials in subjects infected with HCV in 2011, is included.


  • Organizational Affiliation

    GlaxoSmithKline, Infectious Diseases Medicines Discovery Unit, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HCV Polymerase
A, B
577Hepatitis C virus subtype 1bMutation(s): 3 
Gene Names: NS5B
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
Binding Affinity Annotations 
IDSourceBinding Affinity
1PV PDBBind:  4KAI IC50: 50 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.198 
  • R-Value Observed: 0.201 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 86.708α = 90
b = 107.451β = 90
c = 126.382γ = 90
Software Package:
Software NamePurpose
SCALAdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
XSCALEdata scaling
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: 2013-05-08
    Type: Initial release
  • Version 1.1: 2013-05-15
    Changes: Other
  • Version 1.2: 2013-05-29
    Changes: Database references
  • Version 1.3: 2014-03-26
    Changes: Database references
  • Version 1.4: 2018-12-12
    Changes: Data collection, Source and taxonomy
  • Version 1.5: 2024-02-28
    Changes: Data collection, Database references, Derived calculations
  • Version 1.6: 2024-03-13
    Changes: Source and taxonomy, Structure summary