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 

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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. kevin.chen@spcorp.com


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
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  • 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
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
FNH
Query on FNH
Download Ideal Coordinates CCD File 
G [auth A](2R)-({N-[(3S)-3-({[(3S,6S)-6-CYCLOHEXYL-5,8-DIOXO-4,7-DIAZABICYCLO[14.3.1]ICOSA-1(20),16,18-TRIEN-3-YL]CARBONYL}AMINO)-2-OXOHEXANOYL]GLYCYL}AMINO)(PHENYL)ACETIC ACID
C41 H55 N5 O8
MRGBFMHIJSOQIX-IMJQVECRSA-N
BME
Query on BME
Download Ideal Coordinates CCD File 
F [auth A]BETA-MERCAPTOETHANOL
C2 H6 O S
DGVVWUTYPXICAM-UHFFFAOYSA-N
ZN
Query on ZN
Download Ideal Coordinates CCD File 
E [auth A],
H [auth C]		ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
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

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Ligand Structure Quality Assessment 


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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