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Basic Characteristics of Mutations
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Mutation Site
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L99F |
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Mutation Site Sentence
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Figure 2C presents another type of atom shift that corresponds to a flip of a ring of residue 3_B (residue 3 in chain B) in the five structures of the V62A/L99F mutant. |
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Mutation Level
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Amino acid level |
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Mutation Type
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nonsynonymous substitution |
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Gene/Protein/Region
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PR |
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Standardized Encoding Gene
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gag-pol
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Genotype/Subtype
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HIV-2 |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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HIV Infections
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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PIs |
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Location
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- |
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Literature Information
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PMID
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33503916
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Title
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Structural Impacts of Drug-Resistance Mutations Appearing in HIV-2 Protease
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Author
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Laville P,Petitjean M,Regad L
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Journal
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Molecules (Basel, Switzerland)
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Journal Info
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2021 Jan 25;26(3):611
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Abstract
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The use of antiretroviral drugs is accompanied by the emergence of HIV-2 resistances. Thus, it is important to elucidate the mechanisms of resistance to antiretroviral drugs. Here, we propose a structural analysis of 31 drug-resistant mutants of HIV-2 protease (PR2) that is an important target against HIV-2 infection. First, we modeled the structures of each mutant. We then located structural shifts putatively induced by mutations. Finally, we compared wild-type and mutant inhibitor-binding pockets and interfaces to explore the impacts of these induced structural deformations on these two regions. Our results showed that one mutation could induce large structural rearrangements in side-chain and backbone atoms of mutated residue, in its vicinity or further. Structural deformations observed in side-chain atoms are frequent and of greater magnitude, that confirms that to fight drug resistance, interactions with backbone atoms should be favored. We showed that these observed structural deformations modify the conformation, volume, and hydrophobicity of the binding pocket and the composition and size of the PR2 interface. These results suggest that resistance mutations could alter ligand binding by modifying pocket properties and PR2 stability by impacting its interface. Our results reinforce the understanding of the effects of mutations that occurred in PR2 and the different mechanisms of PR2 resistance.
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Sequence Data
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-
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