title: Elucidation of the structure of retroviral proteases: a reminiscence.
abstract: Determinations of only a very few protein structures had consequences comparable to the impact exerted by the structure of the protease encoded by HIV-1, published just over 25 years ago. The structure of this relatively small protein and its cousins from other retroviruses provided a clear target for a spectacularly successful structure-assisted drug design effort that offered new hope for controlling the then-escalating AIDS epidemic. This reminiscence is limited primarily to work conducted at the National Cancer Institute, and is not meant to be a comprehensive history of the field, but is rather an attempt to provide a very personal account of how the structures of this most thoroughly studied crystallographic target were determined.
authors.affiliation: Department of Crystallography, Faculty of Chemistry, A. Mickiewicz University and Center for Biocrystallographic Research, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Jaskolski
authors.affiliation: Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Miller
authors.affiliation: Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Mohana Rao
authors.affiliation: Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD, USA.
authors.forename: Alla
authors.initials: A
authors.lastname: Gustchina
authors.affiliation: Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Wlodawer
mesh_terms: D018360:Crystallography, X-Ray; D055808:Drug Discovery / Q000266:history; D015658:HIV Infections / Q000188:drug therapy / Q000266:history / Q000821:virology; D016333:HIV Protease / Q000737:chemistry / Q000266:history*; D017320:HIV Protease Inhibitors / Q000266:history / Q000627:therapeutic use; D015497:HIV-1 / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D008958:Models, Molecular; D054547:National Cancer Institute (U.S.) / Q000266:history; D020836:Protein Structure, Quaternary; D014481:United States
chemical_list: D017320:HIV Protease Inhibitors; D016333:HIV Protease
keywords: HIV; crystal structures; drug design; inhibitors; protease