title: Molecular dynamics studies of the full-length integrase-DNA complex.
abstract: We have carried out a molecular dynamics (MD) simulation of full-length HIV-1 integrase (IN) dimer complexed with viral DNA with the aim of gaining information about the enzyme motion and investigating the movement of the catalytic flexible loop (residues 140-149) thought to be essential in the catalytic mechanism of IN. During the simulation, we observed quite a different behavior of this region in the presence or absence of the viral DNA. In particular, the MD results underline the crucial role of the residue Tyr143 in the mechanism of integration of viral DNA into the host chromosome. The present findings confirm the experimental data (e.g., site-directed mutagenesis experiments) showing that the loop is involved in the integration reactions and its mobility is correlated with the catalytic activity of HIV-1 integrase.
authors.affiliation: Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, Italy. ldeluca@pharma.unime.it
authors.forename: Laura
authors.initials: L
authors.lastname: De Luca
authors.forename: Giulio
authors.initials: G
authors.lastname: Vistoli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pedretti
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Barreca
authors.forename: Alba
authors.initials: A
authors.lastname: Chimirri
mesh_terms: D020134:Catalytic Domain; D003198:Computer Simulation; D004279:DNA, Viral / Q000737:chemistry*; D019281:Dimerization; D019427:HIV Integrase / Q000737:chemistry*; D015497:HIV-1 / Q000737:chemistry*; D011487:Protein Conformation; D014443:Tyrosine / Q000737:chemistry*
chemical_list: D004279:DNA, Viral; D014443:Tyrosine; D019427:HIV Integrase