2A4Q

HCV NS3 protease with NS4a peptide and a covalently bound macrocyclic ketoamide compound.

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.45 Å
  • R-Value Free: 0.274 
  • R-Value Work: 0.191 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history. 


Literature

Synthesis and Biological Activity of Macrocyclic Inhibitors of Hepatitis C Virus (HCV) NS3 Protease

Chen, K.X., Njoroge, F.G., Prongay, A., Pichardo, J., Madison, V., Girijavallabhan, V.

(2005) Bioorg Med Chem Lett 15: 4475-4478

  • DOI: https://doi.org/10.1016/j.bmcl.2005.07.033
  • Primary Citation of Related Structures:  
    2A4Q

  • PubMed Abstract: 

    The 17-membered phenylalanine-based macrocycle 6 was prepared starting from 3-iodo-phenylalanine. Macrocyclization of alkene phenyl iodide 5 was effected through a palladium-catalyzed Heck reaction. The macrocyclic alpha-ketoamides were active inhibitors of the HCV NS3 protease, with the C-terminal acids and amides being more potent than tert-butyl esters.

    • Organizational Affiliation: 

    Schering-Plough Research Institute, 2015 Galloping Hill Road, K-15-3-3545, Kenilworth, NJ 07033, USA. [email protected]


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
NS3 protease/helicase'
A, C
200Hepacivirus hominisMutation(s): 0 
UniProt
Find proteins for Q91RS4 (Hepacivirus hominis)
Explore Q91RS4 
Go to UniProtKB:  Q91RS4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ91RS4
Sequence Annotations
Expand
  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
NS4a peptide
B, D
23N/AMutation(s): 1 
UniProt
Find proteins for O39914 (Hepacivirus hominis)
Explore O39914 
Go to UniProtKB:  O39914
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO39914
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
FNH PDBBind:  2A4Q Ki: 66 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.45 Å
  • R-Value Free: 0.274 
  • R-Value Work: 0.191 
  • Space Group: H 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 224.923α = 90
b = 224.923β = 90
c = 75.317γ = 120
Software Package:
Software NamePurpose
HKL-2000data collection
SCALEPACKdata scaling
X-PLORmodel building
X-PLORrefinement
HKL-2000data reduction
X-PLORphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


View more in-depth experimental data
Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-07-04
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2021-10-20
    Changes: Database references, Derived calculations