2L94

Structure of the HIV-1 frameshift site RNA bound to a small molecule inhibitor of viral replication


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 50 
  • Conformers Submitted: 10 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Structure of the HIV-1 Frameshift Site RNA Bound to a Small Molecule Inhibitor of Viral Replication.

Marcheschi, R.J.Tonelli, M.Kumar, A.Butcher, S.E.

(2011) ACS Chem Biol 6: 857-864

  • DOI: https://doi.org/10.1021/cb200082d
  • Primary Citation of Related Structures:  
    2L94

  • PubMed Abstract: 

    Programmed -1 translational frameshifting is an essential event in the replication cycle of HIV. Frameshifting is required for expression of the viral Pol proteins, and drug-like molecules that target this process may inhibit HIV replication. A small molecule stimulator of HIV-1 frameshifting and inhibitor of viral replication, DB213 (RG501), was previously discovered from a high-throughput screen. However, the mechanistic basis for this compound's effects was unknown, and to date no structural information exists for small molecule effectors of frameshifting. Here, we investigate the binding of DB213 to the frameshift site RNA and have determined the structure of this complex by NMR. Binding of DB213 stabilizes the RNA and increases its melting temperature by 10 °C. The ligand binds to a primary site on the RNA stem-loop, although nonspecific interactions are also detected. The compound binds in the major groove and spans a distance of 9 base pairs. DB213 hydrogen bonds to phosphate groups on opposite sides of the major groove and alters the conformation of a conserved GGA bulge in the RNA. This study may provide a starting point for structure-based optimization of compounds targeting the HIV-1 frameshift site RNA.


  • Organizational Affiliation

    Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.


Macromolecules
Find similar nucleic acids by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains LengthOrganismImage
RNA_(45-MER)45N/A
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
L94
Query on L94

Download Ideal Coordinates CCD File 
B [auth A]N'-{(Z)-amino[4-(amino{[3-(dimethylammonio)propyl]iminio}methyl)phenyl]methylidene}-N,N-dimethylpropane-1,3-diaminium
C18 H36 N6
QAWYYAYHHZQCLB-UHFFFAOYSA-R
Binding Affinity Annotations 
IDSourceBinding Affinity
L94 PDBBind:  2L94 Kd: 3.60e+5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 50 
  • Conformers Submitted: 10 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-06-15
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2011-08-31
    Changes: Database references
  • Version 1.3: 2023-06-14
    Changes: Data collection, Database references, Derived calculations, Other
  • Version 1.4: 2024-05-15
    Changes: Data collection, Database references