Journal article
The role of select subtype polymorphisms on HIV-1 protease conformational sampling and dynamics
X Huang, MD Britto, JL Kear-Scott, CD Boone, JR Rocca, C Simmerling, R Mckenna, M Bieri, PR Gooley, BM Dunn, GE Fanucci
Journal of Biological Chemistry | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2014
Open access
Abstract
HIV-1 protease is an essential enzyme for viral particle maturation and is a target in the fight against HIV-1 infection worldwide. Several natural polymorphisms are also associated with drug resistance. Here, we utilized both pulsed electron double resonance, also called double electron-electron resonance, and NMR 15N relaxation measurements to characterize equilibrium conformational sampling and backbone dynamics of an HIV-1 protease construct containing four specific natural polymorphisms commonly found in subtypes A, F, and CRF-01 A/E. Results show enhanced backbone dynamics, particularly in the flap region, and the persistence of a novel conformational ensemble that we hypothesize is an..
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Awarded by National Institute of Allergy and Infectious Diseases
Funding Acknowledgements
This work was supported, in whole or in part, by National Institutes of Health Grants S10 RR031603, R01 GM105409 (to G. E. F.), and R37 AI28571 (to B. M. D.). This work was also supported by National Science Foundation Grant MBC-0746533 from the University of Florida Center for AIDS Research, National High Magnetic Field Laboratory user program, and National High Magnetic Field Laboratory-In-House Research Program.