1RTL

CRYSTAL STRUCTURE OF HCV NS3 PROTEASE DOMAIN: NS4A PEPTIDE COMPLEX WITH COVALENTLY BOUND PYRROLIDINE-5,5-TRANSLACTAM INHIBITOR

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.75 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.182 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


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


Literature

Pyrrolidine-5,5-trans-lactams. 4. Incorporation of a P3/P4 urea leads to potent intracellular inhibitors of hepatitis C virus NS3/4A protease

Slater, M.J., Amphlett, E.M., Andrews, D.M., Bamborough, P., Carey, S.J., Johnson, M.R., Jones, P.S., Mills, G., Parry, N.R., Somers, D.O., Stewart, A.J., Skarzynski, T.

(2003) Org Lett 5: 4627-4630

  • DOI: https://doi.org/10.1021/ol035826v
  • Primary Citation of Related Structures:  
    1RTL

  • PubMed Abstract: 

    [reaction: see text] In this, the first of two Letters, we describe how a P3/P4 urea linking unit was used to greatly enhance the biochemical and replicon potency of inhibitors based upon the pyrrolidine-5,5-trans-lactam template. Compound 7b demonstrated a 100 nM IC(50) in the replicon cell-based surrogate HCV assay.

    • Organizational Affiliation: 

    GlaxoSmithKline Medicines Research Center, Gunnels Wood Road, Stevenage, SG1 2NY, UK. martin.j.slater@gsk.com


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
NS3 protease/helicase
A, B
200Hepacivirus hominisMutation(s): 1 
Gene Names: H STRAIN
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
NS4A COFACTOR
C, D
23N/AMutation(s): 0 
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 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CPX
Query on CPX
Download Ideal Coordinates CCD File 
F [auth A]N-[(2R,3S)-1-((2S)-2-{[(CYCLOPENTYLAMINO)CARBONYL]AMINO}-3-METHYLBUTANOYL)-2-(1-FORMYL-1-CYCLOBUTYL)PYRROLIDINYL]CYCLOPROPANECARBOXAMIDE
C24 H38 N4 O4
GCDRFILPPBOJLM-UFYCRDLUSA-N
ZN
Query on ZN
Download Ideal Coordinates CCD File 
E [auth A],
G [auth B]		ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
CPX PDBBind:  1RTL IC50: 2600 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.75 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.182 
  • Space Group: H 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 224.082α = 90
b = 224.082β = 90
c = 75.694γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling

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: 2004-12-14
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2021-10-27
    Changes: Database references, Derived calculations