title: The 80's loop (residues 78 to 85) is important for the differential activity of retroviral proteases.
abstract: The abundance of structural data available for retroviral proteases affords a unique opportunity to investigate structure activity relationships. Our approach attempts to genetically engineer an HIV (human immunodeficiency virus)-1 protease that is functionally equivalent to the HIV-2 and the SIV (simian immunodeficiency virus) enzymes and conversely to engineer an HIV-2 protease that is functionally equivalent to the HIV-1 enzyme. For this purpose, the HIV-2 and SIV proteases were cloned and characterized in an Escherichia coli (E. coli) assay system along with 33 engineered HIV-1 and HIV-2 enzymes. The results of these experiments show that a relatively large S1 or S1' subsite volume, which is likely determined by the conformation of the 80's loop (residues 78 to 85), is necessary to fully accommodate the HIV-1 protease specificity site AETF*YCDG (the asterisk indicates the location scissile bond) during productive binding.
authors.affiliation: Department of Molecular Genetics, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA.
authors.forename: J
authors.initials: J
authors.lastname: Stebbins
authors.forename: E M
authors.initials: EM
authors.lastname: Towler
authors.forename: M G
authors.initials: MG
authors.lastname: Tennant
authors.forename: I C
authors.initials: IC
authors.lastname: Deckman
authors.forename: C
authors.initials: C
authors.lastname: Debouck
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004926:Escherichia coli / Q000235:genetics; D015685:Fusion Proteins, gag-pol / Q000378:metabolism; D015683:Gene Products, gag / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D017958:Lentiviruses, Primate / Q000201:enzymology*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism; D011487:Protein Conformation; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins; D013379:Substrate Specificity
chemical_list: D015685:Fusion Proteins, gag-pol; D015683:Gene Products, gag; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; D016282:Aspartic Acid Endopeptidases