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- W2331431498 abstract "Programmed −1 ribosomal frameshifting (−1 PRF) stimulated by mRNA pseudoknots regulates gene expression in many viruses, making pseudoknots potential targets for anti-viral drugs. The mechanism by which pseudoknots trigger −1 PRF, however, remains controversial, with several competing models. Recent work showed that high −1 PRF efficiency was linked to high pseudoknot conformational plasticity via the formation of alternate conformers. We tested whether pseudoknots bound with an anti-frameshifting ligand exhibited a similar correlation between conformational plasticity and −1 PRF efficiency by measuring the effects of a ligand that was found to inhibit −1 PRF in the SARS coronavirus on the conformational dynamics of the SARS pseudoknot. Using single-molecule force spectroscopy to unfold pseudoknots mechanically, we found that the ligand binding effectively abolished the formation of alternate conformers. This result extends the connection between −1 PRF and conformational dynamics and, moreover, suggests that targeting the conformational dynamics of pseudoknots may be an effective strategy for anti-viral drug design." @default.
- W2331431498 created "2016-06-24" @default.
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- W2331431498 date "2014-01-28" @default.
- W2331431498 modified "2023-10-10" @default.
- W2331431498 title "Anti-frameshifting Ligand Reduces the Conformational Plasticity of the SARS Virus Pseudoknot" @default.
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- W2331431498 doi "https://doi.org/10.1021/ja410344b" @default.
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