title: Crystal structures of HIV-1 reverse transcriptase with picomolar inhibitors reveal key interactions for drug design.
abstract: X-ray crystal structures at 2.9 Å resolution are reported for two complexes of catechol diethers with HIV-1 reverse transcriptase. The results help elucidate the structural origins of the extreme antiviral activity of the compounds. The possibility of halogen bonding between the inhibitors and Pro95 is addressed. Structural analysis reveals key interactions with conserved residues P95 and W229 of importance for design of inhibitors with high potency and favorable resistance profiles.
authors.affiliation: Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, United States.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Frey
authors.forename: Mariela
authors.initials: M
authors.lastname: Bollini
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Mislak
authors.forename: José A
authors.initials: JA
authors.lastname: Cisneros
authors.forename: Ricardo
authors.initials: R
authors.lastname: Gallardo-Macias
authors.forename: William L
authors.initials: WL
authors.lastname: Jorgensen
authors.forename: Karen S
authors.initials: KS
authors.lastname: Anderson
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry*; D001966:Bromine / Q000737:chemistry; D018360:Crystallography, X-Ray; D015195:Drug Design; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D006219:Halogens / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry*
chemical_list: D000998:Antiviral Agents; D006219:Halogens; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D001966:Bromine