3GYN

Crystal structure of HCV NS5B polymerase with a novel monocyclic dihydropyridinone inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.15 Å
  • R-Value Free: 0.276 
  • R-Value Work: 0.225 
  • R-Value Observed: 0.228 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

5,5'- and 6,6'-dialkyl-5,6-dihydro-1H-pyridin-2-ones as potent inhibitors of HCV NS5B polymerase.

Ellis, D.A.Blazel, J.K.Tran, C.V.Ruebsam, F.Murphy, D.E.Li, L.S.Zhao, J.Zhou, Y.McGuire, H.M.Xiang, A.X.Webber, S.E.Zhao, Q.Han, Q.Kissinger, C.R.Lardy, M.Gobbi, A.Showalter, R.E.Shah, A.M.Tsan, M.Patel, R.A.LeBrun, L.A.Kamran, R.Bartkowski, D.M.Nolan, T.G.Norris, D.A.Sergeeva, M.V.Kirkovsky, L.

(2009) Bioorg Med Chem Lett 19: 6047-6052

  • DOI: https://doi.org/10.1016/j.bmcl.2009.09.051
  • Primary Citation of Related Structures:  
    3GYN, 3IGV

  • PubMed Abstract: 

    The discovery of 5,5'- and 6,6'-dialkyl-5,6-dihydro-1H-pyridin-2-ones as potent inhibitors of the HCV RNA-dependent RNA polymerase (NS5B) is described. Several of these agents also display potent antiviral activity in cell culture experiments (EC50 <0.10 microM). In vitro DMPK data for selected compounds as well as crystal structures of representative inhibitors complexed with the NS5B protein are also disclosed.


  • Organizational Affiliation

    Anadys Pharmaceuticals, Inc., 3115 Merryfield Row, San Diego, CA 92121, USA.


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
B42
Query on B42

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
N-{3-[(5R)-1-cyclopentyl-4-hydroxy-5-methyl-5-(3-methylbutyl)-2-oxo-1,2,5,6-tetrahydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl}methanesulfonamide
C24 H34 N4 O6 S2
TXEOLWVIZKSKML-XMMPIXPASA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
B42 Binding MOAD:  3GYN IC50: 47 (nM) from 1 assay(s)
PDBBind:  3GYN IC50: 61 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.15 Å
  • R-Value Free: 0.276 
  • R-Value Work: 0.225 
  • R-Value Observed: 0.228 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 85.864α = 90
b = 106.391β = 90
c = 126.567γ = 90
Software Package:
Software NamePurpose
CrystalCleardata collection
EPMRphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-12-08
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2021-10-13
    Changes: Database references, Derived calculations
  • Version 1.3: 2024-02-21
    Changes: Data collection