title: Structure of HIV-1 RT/TIBO R 86183 complex reveals similarity in the binding of diverse nonnucleoside inhibitors.
abstract: We report the structure of HIV-1 reverse transcriptase (RT) complexed with the nonnucleoside inhibitor TIBO R 86183 at 3.0 A resolution. Comparing this structure with those of complexes of HIV-1 RT/alpha-APA R 95845 and HIV-1 RT/nevirapine provides a basis for understanding the nature of nonnucleoside inhibitor binding, the structure of the binding site and the interactions between the bound inhibitors and surrounding amino acid residues as well as for understanding mechanisms of inhibition by and resistance to nonnucleoside inhibitors. All three inhibitors considered assume a similar butterfly-like shape and bind to HIV-1 RT in a very similar way. Important differences occur in the conformation of amino acid residues that form the binding pocket.
authors.affiliation: Center for Advanced Biotechnology and Medicine (CABM), Piscataway, New Jersey 08854-5638, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ding
authors.forename: K
authors.initials: K
authors.lastname: Das
authors.forename: H
authors.initials: H
authors.lastname: Moereels
authors.forename: L
authors.initials: L
authors.lastname: Koymans
authors.forename: K
authors.initials: K
authors.lastname: Andries
authors.forename: P A
authors.initials: PA
authors.lastname: Janssen
authors.forename: S H
authors.initials: SH
authors.lastname: Hughes
authors.forename: E
authors.initials: E
authors.lastname: Arnold
mesh_terms: D000081:Acetamides / Q000737:chemistry / Q000378:metabolism; D000098:Acetophenones / Q000737:chemistry / Q000378:metabolism; D000814:Aniline Compounds / Q000737:chemistry / Q000378:metabolism; D000998:Antiviral Agents / Q000378:metabolism; D001569:Benzodiazepines / Q000378:metabolism*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000201:enzymology*; D006801:Humans; D007093:Imidazoles / Q000378:metabolism*; D008956:Models, Chemical; D019829:Nevirapine; D009705:Nucleosides / Q000037:antagonists & inhibitors / Q000378:metabolism; D011487:Protein Conformation; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase / Q000737:chemistry* / Q000378:metabolism*; D018894:Reverse Transcriptase Inhibitors / Q000378:metabolism
chemical_list: D000081:Acetamides; D000098:Acetophenones; D000814:Aniline Compounds; D000998:Antiviral Agents; D007093:Imidazoles; D009705:Nucleosides; D011725:Pyridines; C086147:R 86183; D018894:Reverse Transcriptase Inhibitors; C095490:alpha-APA R 95845; D001569:Benzodiazepines; D019829:Nevirapine; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase