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Direct interplay between stereochemistry and conformational preferences in aminoacylated oligoribonucleotides.

ABSTRACT: To address the structural and dynamical consequences of amino-acid attachment at 2'- or 3'-hydroxyls of the terminal ribose in oligoribonucleotides, we have performed an extensive set of molecular dynamics simulations of model aminoacylated RNA trinucleotides. Our simulations suggest that 3'-modified trinucleotides exhibit higher solvent exposure of the aminoacylester bond and may be more susceptible to hydrolysis than their 2' counterparts. Moreover, we observe an invariant adoption of well-defined collapsed and extended conformations for both stereoisomers. We show that the average conformational preferences of aminoacylated trinucleotides are determined by their nucleotide composition and are fine-tuned by amino-acid attachment. Conversely, solvent exposure of the aminoacylester bond depends on the attachment site, the nature of attached amino acid and the strength of its interactions with the bases. Importantly, aminoacylated CCA trinucleotides display a systematically higher solvent exposure of the aminoacylester bond and a weaker dependence of such exposure on sidechain interactions than other trinucleotides. These features could facilitate hydrolytic release of the amino acid, especially for 3' attachment, and may have contributed to CCA becoming the universal acceptor triplet in tRNAs. Our results provide novel atomistic details about fundamental aspects of biological translation and furnish clues about its primordial origins.

SUBMITTER: Polyansky AA

PROVIDER: S-EPMC6868383 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Direct interplay between stereochemistry and conformational preferences in aminoacylated oligoribonucleotides.

Polyansky Anton A AA Kreuter Mathias M Sutherland John D JD Zagrovic Bojan B

Nucleic acids research 20191201 21

To address the structural and dynamical consequences of amino-acid attachment at 2'- or 3'-hydroxyls of the terminal ribose in oligoribonucleotides, we have performed an extensive set of molecular dynamics simulations of model aminoacylated RNA trinucleotides. Our simulations suggest that 3'-modified trinucleotides exhibit higher solvent exposure of the aminoacylester bond and may be more susceptible to hydrolysis than their 2' counterparts. Moreover, we observe an invariant adoption of well-def ...[more]

PMID: 31612955

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Project description:Thioredoxin reductases (TrxRs) are flavin-containing dithioloxidoreductases that couple reduction equivalents from the soluble NAD(P)H pool to the soluble protein thioredoxin (Trx). Previous crystallographic studies of the Escherichia coli enzyme ( ecTrxR) have shown that low molecular weight TrxRs can adopt two distinct conformations: the first (FO) is required for the oxidation of the flavin cofactor and the generation of reduced Trx; the second (FR) is adopted for the reduction of the flavin by NAD(P)H. Here, protein electrochemistry has been used to interrogate the equilibrium between the oxidized and reduced conformations of the ecTrxR and a novel, low molecular weight TrxR from the thermophilic archaeon Thermoplasma acidophilum ( taTrxR) that is characterized structurally and biochemically in the accompanying paper [Hernandez et al. (2008) Biochemistry 47, 9728-9737]. A reversible electrochemical response is observed that reveals a dynamic behavior dependent upon the temperature of the experiment. At low temperatures (283 K) a broad, quasi-reversible electrochemical envelope is observed centered at a value of approximately -300 mV and displaying a peak width of over 150 mV. The voltammetric response sharpens dramatically as the temperature increases, becoming much more reversible (as determined by peak separation and peak width). The overall potential and shape of the voltammetric data indicate that the flavin (FAD/FADH 2) and disulfide/dithiol couples are very close in thermodynamic potentials, and the data are interpreted in terms of the model of two-state conformational change between flavin reducing (FR) and flavin oxidizing (FO) states, where the difference in potential for the flavin and disulfide cofactors must be within 40 mV of one another. In this model, the low temperature peak broadening is interpreted as an indication of a heterogeneous population of TrxR conformations that exist at low temperature; at higher temperatures, FO and FR conformers can rapidly interconvert, and voltammetry reports upon an average potential of the conformations.

Dataset Information

Direct interplay between stereochemistry and conformational preferences in aminoacylated oligoribonucleotides.

Publications

Direct interplay between stereochemistry and conformational preferences in aminoacylated oligoribonucleotides.

Similar Datasets

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