کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10870184 1073992 2014 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک دانش گیاه شناسی
پیش نمایش صفحه اول مقاله
Effects of PRE and POST therapy drug-pressure selected mutations on HIV-1 protease conformational sampling
چکیده انگلیسی
Conformational sampling of pre- and post-therapy subtype B HIV-1 protease sequences derived from a pediatric subject infected via maternal transmission with HIV-1 were characterized by double electron-electron resonance spectroscopy. The conformational ensemble of the PRE construct resembles native-like inhibitor bound states. In contrast, the POST construct, which contains accumulated drug-pressure selected mutations, has a predominantly semi-open conformational ensemble, with increased populations of open-like states. The single point mutant L63P, which is contained in PRE and POST, has decreased dynamics, particularly in the flap region, and also displays a closed-like conformation of inhibitor-bound states. These findings support our hypothesis that secondary mutations accumulate in HIV-1 protease to shift conformational sampling to stabilize open-like conformations, while maintaining the predominant semi-open conformation for activity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: FEBS Letters - Volume 588, Issue 17, 25 August 2014, Pages 3123-3128
نویسندگان
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