2FCX

HIV-1 DIS kissing-loop in complex with neamine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.292 
  • R-Value Work: 0.267 
  • R-Value Observed: 0.267 

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Ligand Structure Quality Assessment 


This is version 2.1 of the entry. See complete history


Literature

Targeting the dimerization initiation site of HIV-1 RNA with aminoglycosides: from crystal to cell.

Ennifar, E.Paillart, J.C.Bodlenner, A.Walter, P.Weibel, J.-M.Aubertin, A.-M.Pale, P.Dumas, P.Marquet, R.

(2006) Nucleic Acids Res 34: 2328-2339

  • DOI: https://doi.org/10.1093/nar/gkl317
  • Primary Citation of Related Structures:  
    2FCX, 2FCY, 2FCZ, 2FD0

  • PubMed Abstract: 

    The kissing-loop complex that initiates dimerization of genomic RNA is crucial for Human Immunodeficiency Virus Type 1 (HIV-1) replication. We showed that owing to its strong similitude with the bacterial ribosomal A site it can be targeted by aminoglycosides. Here, we present its crystal structure in complex with neamine, ribostamycin, neomycin and lividomycin. These structures explain the specificity for 4,5-disubstituted 2-deoxystreptamine (DOS) derivatives and for subtype A and subtype F kissing-loop complexes, and provide a strong basis for rational drug design. As a consequence of the different topologies of the kissing-loop complex and the A site, these aminoglycosides establish more contacts with HIV-1 RNA than with 16S RNA. Together with biochemical experiments, they showed that while rings I, II and III confer binding specificity, rings IV and V are important for affinity. Binding of neomycin, paromomycin and lividomycin strongly stabilized the kissing-loop complex by bridging the two HIV-1 RNA molecules. Furthermore, in situ footprinting showed that the dimerization initiation site (DIS) of HIV-1 genomic RNA could be targeted by these aminoglycosides in infected cells and virions, demonstrating its accessibility.


  • Organizational Affiliation

    UPR 9002 du CNRS conventionnée à l'Université Louis Pasteur, IBMC 15 rue René Descartes, 67084, Strasbourg cedex, France.


Macromolecules

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Entity ID: 1
MoleculeChains LengthOrganismImage
HIV-1 DIS RNA
A, B
23N/A
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.292 
  • R-Value Work: 0.267 
  • R-Value Observed: 0.267 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 27.005α = 90
b = 113.395β = 90
c = 95.038γ = 90
Software Package:
Software NamePurpose
CNSrefinement
HKL-2000data reduction
SCALEPACKdata scaling
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-05-16
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Derived calculations, Structure summary
  • Version 2.1: 2024-02-14
    Changes: Data collection, Database references, Structure summary