title: [Mechanism of action of aspartic proteases. III. Conformational characteristics of HIV-1 protease inhibitor JG-365].
abstract: A set of conformations was shown to be characteristic of the free-state spatial structure of substrate-like inhibitor JG-365 for aspartic protease from HIV-1. Among them, the lowest-energy conformations have a folded form of the peptide backbone. The inhibitor has a noncleavable hydroxyethylamine group with an additional chiral center in its structure. Our calculations showed that only the S-isomer of the inhibitor displays conformational characteristics that practically coincide with those of the native substrate for HIV-1 protease. One of the calculated conformations with a completely extended main chain and a relative energy of 9.5 kcal/mol very closely mimics the experimentally observed structure of the inhibitor in the enzyme-inhibitor complex. The realization of this structure is unlikely for a free inhibitor, because it has only a small number of interresidual noncovalent interactions in the extended conformation; these are presumably compensated for by intermolecular interactions at the active site of the enzyme.
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia. popov@enzyme.siobc.ras.ru
authors.forename: M E
authors.initials: ME
authors.lastname: Popov
authors.forename: I V
authors.initials: IV
authors.lastname: Kashparov
authors.forename: L D
authors.initials: LD
authors.lastname: Rumsh
authors.forename: E M
authors.initials: EM
authors.lastname: Popov
mesh_terms: D016282:Aspartic Acid Endopeptidases / Q000737:chemistry; D016333:HIV Protease / Q000737:chemistry*; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D017320:HIV Protease Inhibitors; D009842:Oligopeptides; C066511:JG 365; D016282:Aspartic Acid Endopeptidases; D016333:HIV Protease