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
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم کشاورزی و بیولوژیک
دانش گیاه شناسی
پیش نمایش صفحه اول مقاله

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
Journal: FEBS Letters - Volume 588, Issue 17, 25 August 2014, Pages 3123-3128
نویسندگان
Jeffrey D. Carter, Estrella G. Gonzales, Xi Huang, Adam N. Smith, Ian Mitchelle S. de Vera, Peter W. D'Amore, James R. Rocca, Maureen M. Goodenow, Ben M. Dunn, Gail E. Fanucci,