4IH5

Hepatitis C Virus polymerase NS5B (BK) with fragment-based compounds


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.194 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

De novo fragment design: a medicinal chemistry approach to fragment-based lead generation.

Talamas, F.X.Ao-Ieong, G.Brameld, K.A.Chin, E.de Vicente, J.Dunn, J.P.Ghate, M.Giannetti, A.M.Harris, S.F.Labadie, S.S.Leveque, V.Li, J.Lui, A.S.McCaleb, K.L.Najera, I.Schoenfeld, R.C.Wang, B.Wong, A.

(2013) J Med Chem 56: 3115-3119

  • DOI: https://doi.org/10.1021/jm4002605
  • Primary Citation of Related Structures:  
    4IH5, 4IH6, 4IH7

  • PubMed Abstract: 

    The use of fragments with low binding affinity for their targets as starting points has received much attention recently. Screening of fragment libraries has been the most common method to find attractive starting points. Herein, we describe a unique, alternative approach to generating fragment leads. A binding model was developed and a set of guidelines were then selected to use this model to design fragments, enabling our discovery of a novel fragment with high LE.


  • Organizational Affiliation

    Hoffmann-La Roche Inc, Pharma Research & Early Development, 340 Kingsland Street, Nutley, New Jersey 07110, United States. franciscotalamas@gmail.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
RNA-directed RNA polymerase
A, B
570Hepatitis C virus (isolate BK)Mutation(s): 0 
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
12R
Query on 12R

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
4-(2-phenylhydrazinyl)-1H-pyrazolo[3,4-d]pyrimidine
C11 H10 N6
TUVLUZBAHCXFSC-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
12R PDBBind:  4IH5 Kd: 7.80e+4 (nM) from 1 assay(s)
Binding MOAD:  4IH5 Kd: 7.80e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.228 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.194 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 85.778α = 90
b = 106.076β = 90
c = 126.432γ = 90
Software Package:
Software NamePurpose
SCALEPACKdata scaling
BUSTER-TNTrefinement
PDB_EXTRACTdata extraction
Blu-Icedata collection
HKL-2000data reduction
REFMACphasing
BUSTERrefinement

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-07-03
    Type: Initial release
  • Version 1.1: 2024-02-28
    Changes: Data collection, Database references, Derived calculations