Dynamics of “Flap” Structures in Three HIV-1 Protease/Inhibitor Complexes Probed by Total Chemical Synthesis and Pulse-EPR Spectroscopy

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• 作者：Vladimir Yu. Torbeev ; H. Raghuraman ; Kalyaneswar Mandal ; Sanjib Senapati ; Eduardo Perozo ; Stephen B. H. Kent
• 刊名：Journal of the American Chemical Society
• 出版年：2009
• 出版时间：January 28, 2009
• 年：2009
• 卷：131
• 期：3
• 页码：884-885
• 全文大小：154K
• 年卷期：v.131,no.3(January 28, 2009)
• ISSN：1520-5126

文摘

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.