Dynamics of "flap" structures in three HIV-1 protease/inhibitor complexes probed by total chemical synthesis and pulse-EPR spectroscopy.
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.
Torbeev
Vladimir Yu
VY
Institute for Biophysical Dynamics, Department of Chemistry, The University of Chicago, Chicago, Illinois 60637, USA.
Raghuraman
H
H
Mandal
Kalyaneswar
K
Senapati
Sanjib
S
Perozo
Eduardo
E
Kent
Stephen B H
SB
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
D017320:HIV Protease Inhibitors; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1