Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10767486 | Biochemical and Biophysical Research Communications | 2007 | 6 Pages |
Abstract
We report molecular modeling and functional confirmation of Ole and HT binding to HIV-1 integrase. Docking simulations identified two binding regions for Ole within the integrase active site. Region I encompasses the conserved D64-D116-E152 motif, while region II involves the flexible loop region formed by amino acid residues 140-149. HT, on the other hand, binds to region II. Both Ole and HT exhibit favorable interactions with important amino acid residues through strong H-bonding and van der Waals contacts, predicting integrase inhibition. To test and confirm modeling predictions, we examined the effect of Ole and HT on HIV-1 integrase activities including 3â²-processing, strand transfer, and disintegration. Ole and HT exhibit dose-dependent inhibition on all three activities, with EC50Â s in the nanomolar range. These studies demonstrate that molecular modeling of target-ligand interaction coupled with structural-activity analysis should facilitate the design and identification of innovative integrase inhibitors and other therapeutics.
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Authors
Sylvia Lee-Huang, Philip Lin Huang, Dawei Zhang, Jae Wook Lee, Ju Bao, Yongtao Sun, Young-Tae Chang, John Zhang, Paul Lee Huang,