4KBI

HCV NS5B GT1B N316Y with CMPD 4


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.06 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.211 
  • R-Value Observed: 0.213 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.5 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
580Hepatitis C virus subtype 1bMutation(s): 4 
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
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
1C0
Query on 1C0

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
5-cyclopropyl-6-{[(7-fluoro-1-hydroxy-1,3-dihydro-2,1-benzoxaborol-5-yl)methyl](methylsulfonyl)amino}-2-(4-fluorophenyl)-N-methyl-1-benzofuran-3-carboxamide
C28 H25 B F2 N2 O6 S
BYQYZNOLMVIJLY-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
1C0 PDBBind:  4KBI IC50: 32 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.06 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.211 
  • R-Value Observed: 0.213 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 86.04α = 90
b = 106.45β = 90
c = 126.49γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing
REFMACrefinement
PDB_EXTRACTdata extraction
JDirectordata collection

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: 2024-02-28
    Changes: Data collection, Database references, Derived calculations
  • Version 1.5: 2024-03-13
    Changes: Source and taxonomy, Structure summary