Keto-enol tautomer of uracil and thymine

The Journal of Physical Chemistry 01/1988; 92(7):1760-1765. DOI: 10.1021/j100318a013
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    ABSTRACT: Ribosomes control the missense error rate of ~10(-4) during translation though quantitative contributions of individual mechanistic steps of the conformational changes yet to be fully determined. Biochemical and biophysical studies led to a qualitative tRNA selection model in which ribosomal A-site residues A1492 and A1493 (A1492/3) flip out in response to cognate tRNA binding, promoting the subsequent reactions, but not in the case of near cognate or non-cognate tRNA. However, this model was recently questioned by X-ray structures revealing conformations of extrahelical A1492/3 and domain closure of the decoding center in both cognate and near-cognate tRNA bound ribosome complexes, suggesting that the non-specific flipping of A1492/3 has no active role in tRNA selection. We explore this question by carrying out molecular dynamics (MD) simulations, aided with fluorescence and NMR experiments, to probe the free energy cost of extrahelical flipping of 1492/3 and the strain energy associated with domain conformational change. Our rigorous calculations demonstrate that the A1492/3 flipping is indeed a specific response to the binding of cognate tRNA, contributing 3kcal/mol to the specificity of tRNA selection. Furthermore, the different A-minor interactions in cognate and near-cognate complexes propagate into the conformational strain and contribute another 4kcal/mol in domain closure. The recent structure of ribosome with features of extrahelical A1492/3 and closed domain in near-cognate complex is reconciled by possible tautomerization of the wobble base pair in mRNA-tRNA. These results quantitatively rationalize other independent experimental observations and explain the ribosomal discrimination mechanism of selecting cognate versus near-cognate tRNA.
    Journal of Molecular Biology 05/2014; · 3.91 Impact Factor
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    ABSTRACT: Electronic-vibrational spectra of both imidazole (I) and the intermediate molecular structure (II) in the intramolecular proton transfer process N1H(I) → N3H(III) have been calculated and analyzed theoretically. The geometries of the molecular structures of I and II in the first ππ* excited state were determined using semi-empirical correlations and the method of hybridized atomic orbitals. The difference in their spectra indicates that the intramolecular proton-transfer mechanism with imidazole (I ↔ III) tautomeric conversion can be identified by electronic-vibrational spectroscopy.
    Journal of Applied Spectroscopy 01/2008; 75(2):168-173. · 0.51 Impact Factor
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    ABSTRACT: UV spectra of pyrimidine nucleotide bases, nucleosides, a number of their derivatives and analogues were investigated in anhydrous DMSO. Effects of interaction with neutral and deprotonated carboxylic group of amino acids on the UV spectra were traced. It was established that methylation of pyrimidine bases at the positions 1 and 5 leads to the 5–12 nm bathochromic shift of the absorption bands. The majority of the Cyt derivatives excluding m3Cyt and isoCyt were shown to interact specifically with neutral carboxylic group. Interactions with deprotonated carboxylic group is characteristic of Ura, Thy and their derivatives, except chx1Ura, s2Ura and dU. The conclusion was drawn that substitution at the positions I and 5 is accompanied by a decrease of a complex formation ability with the both forms of carboxylic groups, but substitution at the position 5 strengthens interaction with neutral carboxylic group but decreases interaction with carboxylate-ion. Biological significance of the results obtained is discussed.
    Biopolymers and Cell 01/2003; 19(1):43-63.