title: Tn5 transposase as a useful platform to simulate HIV-1 integrase inhibitor binding mode.
abstract: The targeting of HIV-1 integrase (IN) for the design of novel antiviral compounds has until now proceeded slowly, mainly due to the lack of three-dimensional structures reporting detail interactions between IN and its DNA substrates as well as the complete enzyme with its three domains. Recently, we have proposed that Tn5 transposase (Tnp) can be used as a useful surrogate model for IN in attempt to address the potential binding modes of Integrase Strand Transfer Inhibitors. In order to strengthen our hypothesis, molecular dynamics simulations of IN inhibitors bound to Tn5 Tnp active site are now reported. A comparison of the obtained results with well documented specific mutations associated with resistance to HIV-1 IN inhibitors confirmed that Tn5 Tnp can provide a valuable platform for the structure-based discovery of new ligands.
authors: Dipartimento Farmaco-Chimico, Università di Messina,Viale Annunziata, I-98168 Messina, Italy. barreca@pharma.unime.it
authors: Maria Letizia
authors: ML
authors: Barreca
authors: Francesco
authors: F
authors: Ortuso
authors: Nunzio
authors: N
authors: Iraci
authors: Laura
authors: L
authors: De Luca
authors: Stefano
authors: S
authors: Alcaro
authors: Alba
authors: A
authors: Chimirri
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D019427:HIV Integrase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D009154:Mutation; D011485:Protein Binding; D013329:Structure-Activity Relationship; D019895:Transposases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism
chemical_list: D019428:HIV Integrase Inhibitors; C473503:Tn5 transposase; D019427:HIV Integrase; D019895:Transposases; C514801:p31 integrase protein, Human immunodeficiency virus 1