2FD0

HIV-1 DIS kissing-loop in complex with lividomycin


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.245 
  • R-Value Observed: 0.245 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 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
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
LIV
Query on LIV

Download Ideal Coordinates CCD File 
C [auth A],
F [auth B]
(2R,3S,4S,5S,6R)-2-((2S,3S,4R,5R,6R)-5-AMINO-2-(AMINOMETHYL)-6-((2R,3S,4R,5S)-5-((1R,2R,3S,5R,6S)-3,5-DIAMINO-2-((2S,3R ,5S,6R)-3-AMINO-5-HYDROXY-6-(HYDROXYMETHYL)-TETRAHYDRO-2H-PYRAN-2-YLOXY)-6-HYDROXYCYCLOHEXYLOXY)-4-HYDROXY-2-(HYDROXYMET HYL)-TETRAHYDROFURAN-3-YLOXY)-4-HYDROXY-TETRAHYDRO-2H-PYRAN-3-YLOXY)-6-(HYDROXYMETHYL)-TETRAHYDRO-2H-PYRAN-3,4,5-TRIOL
C29 H55 N5 O18
DBLVDAUGBTYDFR-SWMBIRFSSA-N
K
Query on K

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A],
G [auth B],
I [auth B]
POTASSIUM ION
K
NPYPAHLBTDXSSS-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
H [auth B]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.245 
  • R-Value Observed: 0.245 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 27.137α = 90
b = 115.335β = 90
c = 95.254γ = 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 1.3: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary