3EYD

Structure of HCV NS3-4A Protease with an Inhibitor Derived from a Boronic Acid


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.180 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Potent inhibitors of HCV-NS3 protease derived from boronic acids.

Venkatraman, S.Wu, W.Prongay, A.Girijavallabhan, V.George Njoroge, F.

(2009) Bioorg Med Chem Lett 19: 180-183

  • DOI: https://doi.org/10.1016/j.bmcl.2008.10.124
  • Primary Citation of Related Structures:  
    3EYD

  • PubMed Abstract: 

    Chronic hepatitis C infection is the leading causes for cirrhosis of the liver and hepatocellular carcinoma, leading to liver failure and liver transplantation. The etiological agent, HCV virus produces a single positive strand of RNA that is processed with the help of serine protease NS3 to produce mature virus. Inhibition of NS3 protease can be potentially used to develop effective drugs for HCV infections. Numerous efforts are now underway to develop potent inhibitors of HCV protease that contain ketoamides as serine traps. Herein we report the synthesis of a series of potent inhibitors that contain a boronic acid as a serine trap. The activity of these compounds were optimized to 200pM. X-ray structure of compound 17 bound to NS3 protease is also discussed.


  • Organizational Affiliation

    Schering Plough Research Institute, K15-MS 3545, Kenilworth, NJ 07033, USA. Srikanth.Venkatraman@spcorp.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HCV NS3
A, C
200hepatitis C virus genotype 1aMutation(s): 0 
Gene Names: ns3
UniProt
Find proteins for P26664 (Hepatitis C virus genotype 1a (isolate 1))
Explore P26664 
Go to UniProtKB:  P26664
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP26664
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
HCV NS4a peptide
B, D
23N/AMutation(s): 1 
UniProt
Find proteins for P26664 (Hepatitis C virus genotype 1a (isolate 1))
Explore P26664 
Go to UniProtKB:  P26664
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP26664
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
BE8
Query on BE8

Download Ideal Coordinates CCD File 
F [auth A][(1R)-2-cyclobutyl-1-({[(1R,2S,5S)-3-(N-{[(1S)-2,2-dimethyl-1-{[methyl(methylsulfonyl)amino]methyl}propyl]carbamoyl}-3-methyl-L-valyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hex-2-yl]carbonyl}amino)ethyl]boronic acid
C29 H54 B N5 O7 S
KGZWDDBJGGJYLY-WKOLOUIMSA-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
BE8 BindingDB:  3EYD Ki: 0.2 (nM) from 1 assay(s)
PDBBind:  3EYD Ki: 0.2 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.180 
  • Space Group: H 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 224.483α = 90
b = 224.483β = 90
c = 75.786γ = 120
Software Package:
Software NamePurpose
ADSCdata collection
X-PLORmodel building
X-PLORrefinement
HKL-2000data reduction
SCALEPACKdata scaling
X-PLORphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-02-10
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2021-10-20
    Changes: Database references, Derived calculations
  • Version 1.3: 2023-12-27
    Changes: Data collection