5E0I

Crystal structure of the HBV capsid Y132A mutant (VCID 8772) in complex with NVR10-001E2 at 1.95A resolution


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.252 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.221 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

High-resolution crystal structure of a hepatitis B virus replication inhibitor bound to the viral core protein.

Klumpp, K.Lam, A.M.Lukacs, C.Vogel, R.Ren, S.Espiritu, C.Baydo, R.Atkins, K.Abendroth, J.Liao, G.Efimov, A.Hartman, G.Flores, O.A.

(2015) Proc Natl Acad Sci U S A 112: 15196-15201

  • DOI: https://doi.org/10.1073/pnas.1513803112
  • Primary Citation of Related Structures:  
    5E0I

  • PubMed Abstract: 

    The hepatitis B virus (HBV) core protein is essential for HBV replication and an important target for antiviral drug discovery. We report the first, to our knowledge, high-resolution crystal structure of an antiviral compound bound to the HBV core protein. The compound NVR-010-001-E2 can induce assembly of the HBV core wild-type and Y132A mutant proteins and thermostabilize the proteins with a Tm increase of more than 10 °C. NVR-010-001-E2 binds at the dimer-dimer interface of the core proteins, forms a new interaction surface promoting protein-protein interaction, induces protein assembly, and increases stability. The impact of naturally occurring core protein mutations on antiviral activity correlates with NVR-010-001-E2 binding interactions determined by crystallography. The crystal structure provides understanding of a drug efficacy mechanism related to the induction and stabilization of protein-protein interactions and enables structure-guided design to improve antiviral potency and drug-like properties.


  • Organizational Affiliation

    Novira Therapeutics, Doylestown, PA 18902; kklumpp@noviratherapeutics.com.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Capsid protein
A, B, C, D, E
A, B, C, D, E, F
157Hepatitis B virus subtype adywMutation(s): 1 
UniProt
Find proteins for P03147 (Hepatitis B virus genotype D subtype adw (isolate United Kingdom/adyw/1979))
Explore P03147 
Go to UniProtKB:  P03147
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03147
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.252 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.221 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 152.6α = 90
b = 88.17β = 103.47
c = 102.25γ = 90
Software Package:
Software NamePurpose
XDSdata reduction
XSCALEdata scaling
Cootmodel building
PHASERphasing
REFMACrefinement

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-12-09
    Type: Initial release
  • Version 1.1: 2015-12-16
    Changes: Database references
  • Version 1.2: 2023-09-27
    Changes: Data collection, Database references, Derived calculations, Refinement description