3CVK

Crystal structure of HCV NS5B polymerase with a novel pyridazinone inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.31 Å
  • R-Value Free: 0.272 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.210 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Hexahydro-pyrrolo- and hexahydro-1H-pyrido[1,2-b]pyridazin-2-ones as potent inhibitors of HCV NS5B polymerase.

Ruebsam, F.Sun, Z.Ayida, B.K.Webber, S.E.Zhou, Y.Zhao, Q.Kissinger, C.R.Showalter, R.E.Shah, A.M.Tsan, M.Patel, R.Lebrun, L.A.Kamran, R.Sergeeva, M.V.Bartkowski, D.M.Nolan, T.G.Norris, D.A.Kirkovsky, L.

(2008) Bioorg Med Chem Lett 18: 5002-5005

  • DOI: https://doi.org/10.1016/j.bmcl.2008.08.017
  • Primary Citation of Related Structures:  
    3CVK

  • PubMed Abstract: 

    Hexahydro-pyrrolo- and hexahydro-1H-pyrido[1,2-b]pyridazin-2-one analogs were discovered as a novel class of inhibitors of genotype 1 HCV NS5B polymerase. Among these, compound 4c displayed potent inhibitory activities in biochemical and replicon assays (IC(50) (1b) <10 nM; EC(50) (1b)=34 nM) as well as good stability towards human liver microsomes (HLM t(1/2) =59 min).


  • Organizational Affiliation

    Anadys Pharmaceuticals, Inc., 3115 Merryfield Row, San Diego, CA 92121, USA. fruebsam@anadyspharma.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
RNA-directed RNA polymerase
A, B
578Hepatitis C virus (isolate BK)Mutation(s): 1 
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
N34
Query on N34

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
N-{3-[1-(3,3-Dimethyl-butyl)-4-hydroxy-2-oxo-1,2,4a,5,6,7-hexahydro-pyrrolo[1,2-b]pyridazin-3-yl]-1,1-dioxo-1,2-dihydro -1lambda6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide
C21 H29 N5 O6 S2
OCQGEVFPTYSQCK-HNNXBMFYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
N34 PDBBind:  3CVK IC50: 10 (nM) from 1 assay(s)
Binding MOAD:  3CVK IC50: 10 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.31 Å
  • R-Value Free: 0.272 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.210 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 86.302α = 90
b = 106.258β = 90
c = 126.225γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
CrystalCleardata collection
HKL-2000data reduction
HKL-2000data scaling
EPMRphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-04-21
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2021-10-20
    Changes: Database references, Derived calculations, Structure summary