3ZT0: Small Molecule Inhibitors Of The Ledgf Site Of Hiv Type 1 Integrase Identified By Fragment Screening And Structure Based Drug Design

Citation:
Abstract
A fragment-based screen against human immunodeficiency virus type 1 (HIV) integrase led to a number of compounds that bound to the lens epithelium derived growth factor (LEDGF) binding site of the integrase catalytic core domain. We determined the crystallographic structures of complexes of the HIV integrase catalytic core domain for 10 of these compounds and quantitated the binding by surface plasmon resonance. We demonstrate that the compounds inhibit the interaction of LEDGF with HIV integrase in a proximity AlphaScreen assay, an assay for the LEDGF enhancement of HIV integrase strand transfer and in a cell based assay. The compounds identified represent a potential framework for the development of a new series of HIV integrase inhibitors that do not bind to the catalytic site of the enzyme.
PDB ID: 3ZT0Download
MMDB ID: 101171
PDB Deposition Date: 2011/7/1
Updated in MMDB: 2012/08
Experimental Method:
x-ray diffraction
Resolution: 1.95  Å
Source Organism:
Similar Structures:
Biological Unit for 3ZT0: dimeric; determined by author and by software (PISA)
Molecular Components in 3ZT0
Label Count Molecule
Proteins (2 molecules)
2
Integrase
Molecule annotation
Chemicals (8 molecules)
1
6
2
2
* Click molecule labels to explore molecular sequence information.

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