Evolution under Drug Pressure Remodels the Folding Free-Energy Landscape of Mature HIV-1 Protease
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- 作者：John M. Louis1 ; johnl@niddk.nih.gov" class="auth_mail" title="E-mail the corresponding author ; Julien Roche1 ; 2 ; julien.roche@nih.gov" class="auth_mail" title="E-mail the corresponding author
- 关键词：HIV-1 ; human immunodeficiency virus type 1 ; PIs ; clinical protease inhibitors ; DRMs ; drug resistance mutations ; PR ; optimized wild-type HIV-1 protease ; PR20 ; extremely drug-resistant variant of PR bearing 19 mutations ; DSC ; differential scanning calorimetry ; DMP323 ; cyclic nonpeptide urea inhibitor ; TROSY ; transverse relaxation optimized spectroscopy ; DRV ; PI darunavir
- 刊名：Journal of Molecular Biology
- 出版年：2016
- 出版时间：3 July 2016
- 年：2016
- 卷：428
- 期：13
- 页码：2780-2792
- 全文大小：1559 K
文摘
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Drug resistance mutations affect the folding landscape of the mature HIV-1 protease.
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10">The unfolding of the protease under pressure is fully reversible.
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15">Binding of inhibitor decreases the folding cooperativity of the protease dimer.
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The multidrug-resistant PR20 exhibits a nearly ideal two-state unfolding transition.
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Selection of drug resistance accounts for optimal folding and function.