title: Dynamics of "flap" structures in three HIV-1 protease/inhibitor complexes probed by total chemical synthesis and pulse-EPR spectroscopy.
abstract: The unliganded form of nitroxide spin-labeled HIV-1 protease and three different complexes with inhibitors were studied by pulse-EPR spectroscopy to determine "interflap" distance distributions in solution. In the unliganded enzyme, we observed a rather broad distribution with three maxima corresponding to three flap conformers; the principal form is a "semiopen/semiopen" conformer. In the complexes with inhibitors, the dominant conformer is an asymmetric "closed/semiopen" form. Moreover, the distance distribution profile is significantly varied among the different inhibitors, which mimic different species on the reaction coordinate for enzyme catalyzed proteolysis.
authors.affiliation: Institute for Biophysical Dynamics, Department of Chemistry, The University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Vladimir Yu
authors.initials: VY
authors.lastname: Torbeev
authors.forename: H
authors.initials: H
authors.lastname: Raghuraman
authors.forename: Kalyaneswar
authors.initials: K
authors.lastname: Mandal
authors.forename: Sanjib
authors.initials: S
authors.lastname: Senapati
authors.forename: Eduardo
authors.initials: E
authors.lastname: Perozo
authors.forename: Stephen B H
authors.initials: SB
authors.lastname: Kent
mesh_terms: D004578:Electron Spin Resonance Spectroscopy; D016333:HIV Protease / Q000737:chemistry* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D017434:Protein Structure, Tertiary
chemical_list: D017320:HIV Protease Inhibitors; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1