3AVA: Crystal Structures Of Novel Allosteric Peptide Inhibitors Of Hiv Integrase In The Ledgf Binding Site

Citation:
Abstract
An optimised method of solution cyclisation gave us access to a series of peptides including SLKIDNLD (2). We investigated the crystallographic complexes of the HIV integrase (HIV-IN) catalytic core domain with 13 of the peptides and identified multiple interactions at the binding site, including hydrogen bonds with residues Thr125 and Gln95, that have not previously been described as being accessible within the binding site. We show that the peptides inhibit the interaction of lens epithelium-derived growth factor (LEDGF) with HIV-IN in a proximity AlphaScreen assay and in an assay for the LEDGF enhancement of HIV-IN strand transfer. The interactions identified represent a potential framework for the development of new HIV-IN inhibitors.
PDB ID: 3AVADownload
MMDB ID: 96464
PDB Deposition Date: 2011/3/2
Updated in MMDB: 2013/06
Experimental Method:
x-ray diffraction
Resolution: 1.7  Å
Source Organism:
Human immunodeficiency virus type 1 (NEW YORK-5 ISOLATE)
Similar Structures:
Biological Unit for 3AVA: tetrameric; determined by author and by software (PISA)
Molecular Components in 3AVA
Label Count Molecule
Proteins (4 molecules)
2
Integrase
Molecule annotation
2
Ledgf Peptide
Molecule annotation
Chemicals (11 molecules)
1
8
2
1
3
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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