Structural Interpretation of J Coupling Constants in Guanosine and Deoxyguanosine: Modeling the Effects of Sugar Pucker, Backbone Conformation, and Base Pairing (original) (raw)
Related papers
Magnetic Resonance in Chemistry, 1996
The scalar coupling constants in uniformly isotope-enriched [ "C, "N] nucleotide 5'-monophosphates (5'-NMPs) and in various non-labelled cyclic nucleotides were investigated. These model compounds yielded an almost complete set of homonuclear and heteronuclear coupling constants in ribonucleotides, the knowledge of which is useful in designing novel heteronuclear NMR experiments and opens up new possibilities in the structure determination of larger nucleic acids. Three sets of heteronuclear coupling constants were obtained: (1) conformation-independent 'H-13C, 'H-15N, "C-"N, 13C-'3C and 1sN-'5N coupling constants in the base, knowledge of which is essential in optimizing and designing new NMR experiments, which use the coherent transfer of magnetization via the J-coupling network in the nucleic acid base and sugar; (2) 'H-I3C coupling constants, 3JH1.wL,2 and 3JH18c8,s, monitoring the glycosidic torsion angle x, give important information on the rotamer distribution around the x angle; a new parameterization of the Karplus equations is presented; and (3) conformationdependent one-bond and multiple bond 'H-I3C coupling constants in the ribose sugar. Conformationally rigid, cyclic, nucleotides were used to determine multiple bond ' H-"C coupling constants in pure N-type and pure S-type sugar rings. Equations were derived for the determination of the fraction S-type sugar, pS, from the three-bond J, couplings 3JH3.c1., 3JH2,c4., 3JHl.c3r and 3JH4c2,. Their values for pure N-and S-type sugar conformations were used to derive Karplus equations, which describe the dependence of these coupling constants on the phase angle, P.
Journal of biomolecular NMR, 2001
The sugar conformation of a DNA decamer was studied with proton-proton 3J coupling constants. Two samples, one comprising stereospecifically labeled 2'-R-2H for all residues and the other 2'-S-2H, were prepared by the method of Kawashima et al. [J. Org. Chem. (1995) 60, 6980-6986; Nucleosides Nucleotides (1995) 14, 333-336], the deuterium labeling being highly stereospecific (> or = 99% for all 2''-2H, > or = 98% for 2'-2H of A, C, and T, and > or = 93% for 2'-2H of G). The 3J values of all H1'-H2' and H1'-H2'' pairs, and several H2'-H3' and H2''-H3' pairs were determined by line fitting of 1D spectra with 0.1-0.2 Hz precision. The observed J coupling constants were explained by the rigid sugar conformation model, and the sugar conformations were found to be between C3'-exo and C2'-endo with phi(m) values of 26 degrees to 44 degrees, except for the second and 3' terminal residues C2 and C10. For the...
J Phys Chem B, 2000
In the present paper, we have analyzed the conformational energy and geometrical parameters of the isolated 2′-deoxyribonucleosides and ribonucleosides. Geometry optimization of these nucleic acid constituents has been undertaken by means of density functional theory with the Becke-Lee-Yang-Parr exchange and correlation functional and split valence basis sets, 6-31G (/) , including nonstandard polarization functions on carbon, nitrogen, and oxygen atoms. For each nucleoside, three major conformers, i.e., C2′-endo/anti, C3′endo/anti, and C3′-endo/syn, have been taken into consideration, where C3′-endo and C2′-endo refer to the north (N)-type and south (S)-type sugar puckering, respectively, and anti and syn designate the orientation of the base with respect to the sugar. In both families (2′-deoxyribonucleosides and ribonucleosides) the anti orientation of the base stabilized by an intramolecular C-H‚‚‚O hydrogen bond formed between the base and the O5′ atom of the sugar moiety corresponds to the lowest energy states. In the 2′-deoxyribonucleosides including uracil, guanine, and adenine bases the lowest energy conformer is C2′-endo/anti, whereas in 2′deoxycytidine the most stable conformer is C3′-endo/anti. In ribonucleosides, the C3′-endo/anti and C2′endo/anti conformers nearly have the same energy, except in cytidine, where the most stable conformer is C3′-endo/anti. Therefore, a general discussion has been devoted to the exceptional cases of 2′-deoxycytidine and cytidine compared to the other nucleosides. The present calculated results have also been compared with those recently reported at the MP2 level by other authors on the 2′-deoxyribonucleosides or smaller model compounds on one hand, and with the experimental results based on a statistical survey of nucleoside crystal structures on the other hand.
Magn Reson Chem, 1981
The relationship between vicinal N M R proton-proton coupling constants and the pseudorotational properties of the sugar ring in nucleosides and nucleotides is reinvestigated. Compared with our earlier study several important improvements are introduced: first, a new empirical generalization of the classical Karplus equation is utilized, which allows an accurate correction for the effects of electronegativity and orientation of substituents on 3J(EIH); second, empirical correlations between the parameters governing the conformation of p-D-furanosides (taken from an analysis of 178 crystal stmctores) were used to define proton-proton torsion angles as a fnnctiou of the pseudorotation parameters P and a,,,; and, third an iterative least-squares computer program was devised to obtain the best fit of the conformational parameters to the experimental coupling constants. N M R data for the sugar ring in the following compounds were taken from the literature and analysed: 3',5'-cy&c nudeotides, a base-stacked nionucleotide, 2'-~ydroarabinonucleosides, or-~-2',2-0-cyclouridine, 2'-and 3'-aminosubstituted ribonucleosides, 2'-and 3'-deoxyribonucleosides. The present results confirm that the conformational properties found in the solid state are, on the whole, preserved in solution.
The Journal of Physical Chemistry B, 2007
The structure and function of RNA molecules are substantially affected by non-Watson-Crick base pairs actively utilizing the 2′-hydroxyl group of ribose. Here we correlate scalar coupling constants across the noncovalent contacts calculated for the cis-and trans-WC/SE (Watson-Crick/sugar edge) RNA base pairs with the geometry of base to base and sugar to base hydrogen bond(s). 23 RNA base pairs from the 32 investigated were found in RNA crystal structures, and the calculated scalar couplings are therefore experimentally relevant with regard to the binding patterns occurring in this class of RNA base pairs. The intermolecular scalar couplings 1h J(N,H), 2h J(N,N), 2h J(C,H), and 3h J(C,N) were calculated for the N-H‚‚‚N and N-H‚‚‚OdC base to base contacts and various noncovalent links between the sugar hydroxyl and RNA base. Also, the intramolecular 1 J(N,H) and 2 J(C,H) couplings were calculated for the amino or imino group of RNA base and the ribose 2′-hydroxyl group involved in the noncovalent interactions. The calculated scalar couplings have implications for validation of local geometry, show specificity for the amino and imino groups of RNA base involved in the linkage, and can be used for discrimination between the cis-and trans-WC/SE base pairs. The RNA base pairs within an isosteric subclass of the WC/SE binding patterns can be further sorted according to the scalar couplings calculated across different local noncovalent contacts. The effect of explicit water inserted in the RNA base pairs on the magnitude of the scalar couplings was calculated, and the data for discrimination between the water-inserted and direct RNA base pairs are presented. The calculated NMR data are significant for structural interpretation of the scalar couplings in the noncanonical RNA base pairs.
The Journal of Physical Chemistry B, 2005
Due to the presence of the 2′-OH hydroxyl group of ribose, RNA molecules utilize an astonishing variability of base pairing patterns to build up their structures and perform the biological functions. Many of the key RNA base pairing families have no counterparts in DNA. In this study, the trans Watson-Crick/sugar edge (trans WC/SE) RNA base pair family has been characterized using quantum chemical and molecular mechanics calculations. Gas-phase optimized geometries from density functional theory (DFT) calculations and RIMP2 interaction energies are reported for the 10 crystallographically identified trans WC/SE base pairing patterns. Further, stable structures are predicted for all of the remaining six possible members of this family not seen in RNAs so far. Among these novel six base pairs, the computations substantially refine two structures suggested earlier based on simple isosteric considerations. For two additional trans WC/SE base pairs predicted in this study, no arrangement was suggested before. Thus, our study brings a complete set of trans WC/SE base pairing patterns. The present results are also contrasted with calculations reported recently for the cis WC/SE base pair family. The computed base pair sizes are in sound correlation with the X-ray data for all WC/SE pairing patterns including both their cis and trans isomers. This confirms that the isostericity of RNA base pairs, which is one of the key factors determining the RNA sequence conservation patterns, originates in the properties of the isolated base pairs. In contrast to the cis structures, however, the isosteric subgroups of the trans WC/SE family differ not only in their H-bonding patterns and steric dimensions but also in the intrinsic strength of the intermolecular interactions. The distribution of the total interaction energy over the sugarbase and base-base contributions is controlled by the cis-trans isomerism.
Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis, 1980
A study has been made by means of ~H-NMR spectroscopy of the syn .~ anti dynamic equilibrium about the glycosidic bond for 5'-deoxyadenosine and some 8-substituted analogues, in different solvents. The results are compared with those previously obtained for the parent adenosine and its 8-substituted analogues. Quantum chemical calculations, with the aid of the Classical Potential and PCILO procedures, were applied to obtain the energies for different conformations of the base in adenosine and 5'-deoxyadenosine, and their 8methyl and 8-halogeno derivatives. Good agreement was found between experimentally determined conformations in solution and those corresponding theoretically to the energy minima, particularly those calculated by the PCILO method. Comparison of the quantitative experimental data with the theoretical results was used to evaluate the validity of the latter and their applicability to studies of nucleoside conformation.
Journal of the American Chemical Society, 2000
Ab initio molecular orbital (MO) and density functional theory (DFT) calculations using a polarized split-valence basis set have been performed on 2-deoxy-D-ribofuranosylamine (2-deoxy-D-erythropentofuranosylamine) in its unprotonated (3) and protonated (4) forms. Structural data confirm three previously reported factors influencing bond lengths in aldofuranosyl rings, and suggest the existence of a new 1,4-lone pair effect. Conformational energy profiles for 3 and 4 were compared to that described recently for 2-deoxy-D-ribofuranose (2-deoxy-D-erythro-pentofuranose) 5. Results show that preferred conformation and energy barriers to pseudorotation are affected significantly by changes in C1 substitution. N-Protonation of 3 reduces pseudorotational barriers, suggesting a more flexible ring relative to the unprotonated molecule. NMR spinspin coupling constants involving C1 and H1 were calculated in 3 and 4 using DFT methods described previously (Cloran et al. J. Phys. Chem. 1999, 103, 3783-3795). Trends in computed couplings as a function of ring conformation and C1 substitution confirm prior predictions based on experimental observations in aminosugars and nucleosides. In general, one-and two-bond J CH and J CC values appear more influenced by O f N substitution and by N-protonation than vicinal 3 J CH and 3 J CC. These results will be useful in studies of related NMR scalar coupling constants in biologically relevant aminosugars and nucleosides, either free in solution or as components of oligosaccharides and oligonucleotides.
Journal of the American Chemical Society, 2000
Ab initio molecular orbital (MO) and density functional theory (DFT) calculations using a polarized split-valence basis set have been performed on 2-deoxy--D-ribofuranosylamine (2-deoxy--D-erythropentofuranosylamine) in its unprotonated (3) and protonated (4) forms. Structural data confirm three previously reported factors influencing bond lengths in aldofuranosyl rings, and suggest the existence of a new 1,4-lone pair effect. Conformational energy profiles for 3 and 4 were compared to that described recently for 2-deoxy--D-ribofuranose (2-deoxy--D-erythro-pentofuranose) 5. Results show that preferred conformation and energy barriers to pseudorotation are affected significantly by changes in C1 substitution. N-Protonation of 3 reduces pseudorotational barriers, suggesting a more flexible ring relative to the unprotonated molecule. NMR spinspin coupling constants involving C1 and H1 were calculated in 3 and 4 using DFT methods described previously (Cloran et al. J. Phys. Chem. 1999, 103, 3783-3795). Trends in computed couplings as a function of ring conformation and C1 substitution confirm prior predictions based on experimental observations in aminosugars and nucleosides. In general, one-and two-bond J CH and J CC values appear more influenced by O f N substitution and by N-protonation than vicinal 3 J CH and 3 J CC . These results will be useful in studies of related NMR scalar coupling constants in biologically relevant aminosugars and nucleosides, either free in solution or as components of oligosaccharides and oligonucleotides.