title: A structure-based approach for targeting the HIV-1 genomic RNA dimerization initiation site.
abstract: Dimerization of the genomic RNA is an important step of the HIV-1 replication cycle. The Dimerization Initiation Site (DIS) promotes dimerization of the viral genome by forming a loop-loop complex between two DIS hairpins. Crystal structures of the DIS loop-loop complex revealed an unexpected and strong similitude with the bacterial 16S ribosomal aminoacyl-tRNA site (A site), which is the target of aminoglycoside antibiotics. As a consequence of these structural and sequence similarities, the HIV-1 DIS also binds some aminoglycosides, not only in vitro, but also ex vivo, in lymphoid cells and in viral particles. Crystal structures of the DIS loop-loop in complex with several aminoglycoside antibiotics provide a detailed-view of the DIS/drug interaction and reveal some hints about possible modifications to increase the drug affinity and/or specificity.
authors: Architecture et réactivité de l'ARN, UPR 9002 CNRS, Institut de Biologie Moléculaire et Cellulaire, 15 rue René Descartes, 67084 Strasbourg, France. e.ennifar@ibmc.u-strasbg.fr
authors: Eric
authors: E
authors: Ennifar
authors: Jean-Christophe
authors: JC
authors: Paillart
authors: Serena
authors: S
authors: Bernacchi
authors: Philippe
authors: P
authors: Walter
authors: Patrick
authors: P
authors: Pale
authors: Jean-Luc
authors: JL
authors: Decout
authors: Roland
authors: R
authors: Marquet
authors: Philippe
authors: P
authors: Dumas
mesh_terms: D000617:Aminoglycosides / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D019281:Dimerization; D016679:Genome, Viral; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009690:Nucleic Acid Conformation; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D000617:Aminoglycosides; D012367:RNA, Viral