1YVF

Hepatitis C virus NS5B RNA-dependent RNA polymerase complex with inhibitor PHA-00729145


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.303 
  • R-Value Work: 0.240 
  • R-Value Observed: 0.240 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Inhibitors of HCV NS5B polymerase. Part 1: Evaluation of the southern region of (2Z)-2-(benzoylamino)-3-(5-phenyl-2-furyl)acrylic acid.

Pfefferkorn, J.A.Greene, M.L.Nugent, R.A.Gross, R.J.Mitchell, M.A.Finzel, B.C.Harris, M.S.Wells, P.A.Shelly, J.A.Anstadt, R.A.Kilkuskie, R.E.Kopta, L.A.Schwende, F.J.

(2005) Bioorg Med Chem Lett 15: 2481-2486

  • DOI: https://doi.org/10.1016/j.bmcl.2005.03.066
  • Primary Citation of Related Structures:  
    1YVF

  • PubMed Abstract: 

    A novel series of nonnucleoside HCV NS5B polymerase inhibitors were prepared from (2Z)-2-(benzoylamino)-3-(5-phenyl-2-furyl)acrylic acid, a high throughput screening lead. SAR studies combined with structure based drug design focusing on the southern heterobiaryl region of the template led to the synthesis of several potent and orally bioavailable lead compounds. X-ray crystallography studies were also performed to understand the interaction of these inhibitors with HCV NS5B polymerase.


  • Organizational Affiliation

    Pfizer Global Research and Development, Michigan Laboratories, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. jeffrey.a.pfefferkorn@pfizer.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HCV NS5B POLYMERASE577Hepacivirus hominisMutation(s): 0 
EC: 2.7.7.48
UniProt
Find proteins for O93077 (Hepacivirus hominis)
Explore O93077 
Go to UniProtKB:  O93077
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO93077
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PH7
Query on PH7

Download Ideal Coordinates CCD File 
D [auth A](2Z)-2-(BENZOYLAMINO)-3-[4-(2-BROMOPHENOXY)PHENYL]-2-PROPENOIC ACID
C22 H16 Br N O4
WLPJLQNKCJWAFL-RGEXLXHISA-N
PO4
Query on PO4

Download Ideal Coordinates CCD File 
B [auth A]PHOSPHATE ION
O4 P
NBIIXXVUZAFLBC-UHFFFAOYSA-K
GOL
Query on GOL

Download Ideal Coordinates CCD File 
E [auth A],
F [auth A],
G [auth A],
H [auth A]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
C [auth A]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Binding Affinity Annotations 
IDSourceBinding Affinity
PH7 PDBBind:  1YVF IC50: 100 (nM) from 1 assay(s)
Binding MOAD:  1YVF IC50: 100 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.303 
  • R-Value Work: 0.240 
  • R-Value Observed: 0.240 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 90.879α = 90
b = 90.879β = 90
c = 188.516γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2005-04-19
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Refinement description
  • Version 1.4: 2024-02-14
    Changes: Data collection, Database references, Derived calculations