ArticleNucleic acids research2000
Importance of discriminator base stacking interactions: molecular dynamics analysis of A73 microhelix(Ala) variants.
Article in Nucleic acids research, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Accurately Modeling RNA Stem-Loops in an Implicit Solvent Environment.Journal of chemical information and modeling · 2024Article
- Probing RNA Structures and Interactions Using Fluorescence Lifetime Analyses.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Double mimicry evades tRNA synthetase editing by toxic vegetable-sourced non-proteinogenic amino acid.Nature communications · 2017Article
- Quantitative sampling of conformational heterogeneity of a DNA hairpin using molecular dynamics simulations and ultrafast fluorescence spectroscopy.Nucleic acids research · 2016Article
- The identity of the discriminator base has an impact on CCA addition.Nucleic acids research · 2015Article
- Molecular Mechanics Investigation of an Adenine-Adenine Non-Canonical Pair Conformational Change.Journal of chemical theory and computation · 2011Article
- Review
- Molecular dynamics simulations of human tRNA Lys,3 UUU: the role of modified bases in mRNA recognition.Nucleic acids research · 2006Article
- Hinge-like motions in RNA kink-turns: the role of the second a-minor motif and nominally unpaired bases.Biophysical journal · 2005Article
- Molecular dynamics simulations of RNA kissing-loop motifs reveal structural dynamics and formation of cation-binding pockets.Nucleic acids research · 2003Article
- Non-Watson-Crick basepairing and hydration in RNA motifs: molecular dynamics of 5S rRNA loop E.Biophysical journal · 2003Article
- Efficient aminoacylation of the tRNA(Ala) acceptor stem: dependence on the 2:71 base pair.RNA (New York, N.Y.) · 2002Article
- Translocation within the acceptor helix of a major tRNA identity determinant.The EMBO journal · 2001Article
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Authors and funding
4 authors.
Funding
Abstract
Transfer of alanine from Escherichia coli alanyl-tRNA synthetase (AlaRS) to RNA minihelices that mimic the amino acid acceptor stem of tRNA(Ala) has been shown, by analysis of variant minihelix aminoacylation activities, to involve a transition state sensitive to changes in the 'discriminator' base at position 73. Solution NMR has indicated that this single-stranded nucleotide is predominantly stacked onto G1 of the first base pair of the alanine acceptor stem helix. We report the activity of a new variant with the adenine at position 73 substituted by its non-polar isostere 4-methylindole (M). Despite lacking N7, this analog is well tolerated by AlaRS. Molecular dynamics (MD) simulations show that the M substitution improves position 73 base stacking over G1, as measured by a stacking lifetime analysis. Additional MD simulations of wild-type microhelix(Ala) and six variants reveal a positive correlation between N73 base stacking propensity over G1 and aminoacylation activity. For the two DeltaN7 variants simulated we found that the propensity to stack over G1 was similar to the analogous variants that contain N7 and we conclude that the decrease in aminoacylation efficiency observed upon deletion of N7 is likely due to loss of a direct stabilizing interaction with the synthetase.
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