1NHU

Hepatitis C virus RNA polymerase in complex with non-nucleoside analogue inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.219 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Non-Nucleoside Analogue Inhibitors Bind to an Allosteric Site on HCV NS5B Polymerase: Crystal Structures and Mechanism of Inhibition

Wang, M.Ng, K.K.S.Cherney, M.M.Chan, L.Yannopoulos, C.G.Bedard, J.Morin, N.Nguyen-Ba, N.Alaoui-Ismaili, M.H.Bethell, R.C.James, M.N.G.

(2003) J Biol Chem 278: 9489-9495

  • DOI: https://doi.org/10.1074/jbc.M209397200
  • Primary Citation of Related Structures:  
    1NHU, 1NHV

  • PubMed Abstract: 

    X-ray crystal structures of two non-nucleoside analogue inhibitors bound to hepatitis C virus NS5B RNA-dependent RNA polymerase have been determined to 2.0 and 2.9 A resolution. These noncompetitive inhibitors bind to the same site on the protein, approximately 35 A from the active site. The common features of binding include a large hydrophobic region and two hydrogen bonds between both oxygen atoms of a carboxylate group on the inhibitor and two main chain amide nitrogen atoms of Ser(476) and Tyr(477) on NS5B. The inhibitor-binding site lies at the base of the thumb domain, near its interface with the C-terminal extension of NS5B. The location of this inhibitor-binding site suggests that the binding of these inhibitors interferes with a conformational change essential for the activity of the polymerase.


  • Organizational Affiliation

    Canadian Institutes for Health Research Group in Protein Structure and Function, Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HEPATITIS C VIRUS NS5B RNA-DEPENDENT RNA POLYMERASE
A, B
578Hepatitis C virus subtype 1bMutation(s): 0 
EC: 2.7.7.48
UniProt
Find proteins for P26663 (Hepatitis C virus genotype 1b (isolate BK))
Explore P26663 
Go to UniProtKB:  P26663
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP26663
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
153
Query on 153

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
(2S)-2-[(2,4-DICHLORO-BENZOYL)-(3-TRIFLUOROMETHYL-BENZYL)-AMINO]-3-PHENYL-PROPIONIC ACID
C24 H18 Cl2 F3 N O3
LAJJKGIZTCCOHY-NRFANRHFSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
153 PDBBind:  1NHU Ki: 2200 (nM) from 1 assay(s)
Binding MOAD:  1NHU Ki: 2200 (nM) from 1 assay(s)
BindingDB:  1NHU IC50: 1800 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.219 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 86.015α = 90
b = 104.684β = 90
c = 126.843γ = 90
Software Package:
Software NamePurpose
SCALEPACKdata scaling
CNSrefinement
CNSphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2003-03-18
    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: 2017-10-11
    Changes: Refinement description
  • Version 1.4: 2023-08-16
    Changes: Data collection, Database references, Derived calculations, Refinement description