2F9U

HCV NS3 protease domain with NS4a peptide and a ketoamide inhibitor with a P2 norborane


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.286 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.194 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Novel Inhibitors of Hepatitis C NS3-NS4A Serine Protease Derived from 2-Aza-bicyclo[2.2.1]heptane-3-carboxylic acid.

Venkatraman, S.Njoroge, F.G.Wu, W.Girijavallabhan, V.Prongay, A.J.Butkiewicz, N.Pichardo, J.

(2006) Bioorg Med Chem Lett 16: 1628-1632

  • DOI: https://doi.org/10.1016/j.bmcl.2005.12.046
  • Primary Citation of Related Structures:  
    2F9U

  • PubMed Abstract: 

    Prolonged hepatitis C infection is the leading cause for cirrhosis of the liver and hepatocellular carcinoma. The etiological agent HCV virus codes a single polyprotein of approximately 3000 amino acids that is processed with the help of a serine protease NS3A to produce structural and non-structural proteins required for viral replication. Inhibition of NS3 protease can potentially be used to develop drugs for treatment of HCV infections. Herein, we report the development of a series of novel NS3 serine protease inhibitors derived from 2-aza-bicyclo[2.2.1]-heptane carboxylic acid with potential therapeutic use for treatment of HCV infections.


  • Organizational Affiliation

    Schering Plough Research Institute, K-15, MS-3545, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. Srikanth.Venkatraman@spcorp.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
NS3 protease/helicase'
A, C
199Hepacivirus hominisMutation(s): 0 
Gene Names: NS3 protease domain ( residues 1027-1207 of the polyprotein).
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
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
polyprotein
B, D
23N/AMutation(s): 1 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
5NH
Query on 5NH

Download Ideal Coordinates CCD File 
F [auth A]1,1-DIMETHYLETHYL [1-CYCLOHEXYL-2-[3-[[[1-[2-[[2-[[2-(DIMETHYLAMINO)-2-OXO-1-PHENYLETHYL]AMINO]-2-OXOETHYL]AMINO]-1,2-DIOXOETHYL]PENTYL]AMINO]CARBONYL]-2-AZABICYCLO[2.2.1]HEPTAN-2-YL]-2-OXOETHYL]CARBAMATE
C39 H58 N6 O8
YGRWTFVDMXHDOB-KTARVVEZSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
E [auth A],
G [auth C]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
5NH PDBBind:  2F9U Ki: 41 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.286 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.194 
  • Space Group: H 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 225.04α = 90
b = 225.04β = 90
c = 75.44γ = 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 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-06-06
    Type: Initial release
  • Version 1.1: 2008-05-01
    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
  • Version 1.4: 2024-03-13
    Changes: Data collection, Source and taxonomy, Structure summary