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R H Sarma

Publications and source records attributed to R H Sarma.

At least 55 records · Page 3Linked to original sources
PubMed1981

Left-handed deoxyribonucleic acid double helix in solution.

Magnetic shielding constants were calculated for the synthetic deoxyribonucleic acid (DNA) double helix poly(dG-dC).poly(dG-dC) from the x, y, and z coordinates of Z-DNA of Rich and co-workers [Wang, A. H-J., Quigley, G. J., Kolpak, F. J., Crawford, J. L., van Boom, J. H., van der Marel, G., & Rich, A. (1979) Nature (London) 282, 680-686)] and B-DNA of Arnott & Hukins [Arnott, S., & Hukins, D. W. L. (1972) Biochem. Biophys. Res. Commun. 47, 1504-1509], taking into account the contribution to shielding from ring current effects and effects from the diamagnetic and paramagnetic components of the atomic magnetic anisotropy. Comparison of the calculated shielding values with the experimentally observed nuclear magnetic resonance shift data for poly(dG-dC).poly(dG-dC) in high salt solution shows striking agreement for Z-DNA and considerable deviation for B-DNA, indicating that this synthetic DNA double helix is high salt solution can assume the spatial configuration of the left-handed Z-DNA double helix known to occur in crystals.

DNA↗
PubMed1980

Conformational flexibility of the 3' acceptor end of transfer ribonucleic acid.

The intimate details of the conformational features and dynamics of the trinucleoside diphosphates CpCpA and ApCpC in aqueous solution have been arrived at by the complete analysis of their proton magnetic resonance spectra. In addition to the right-handed stacked species in which the phosphodiester torsions conform to the gauche-gauche domains, sugar puckers 3E, C4'-C5 approximately equal to 60 degrees, C5'-O5' approximately 180 degrees, C3'-O3' approximately equal to 205 degrees, and chi CN approximately equal to 40 degrees, the trimers display a variety of spatial configurations, an important one being a bulged configuration in which the central nucleotide unit is bulged out, enabling stacking interactions between the end units. It is further shown that the 3' acceptor end of tRNA, CpCpA, displays considerable flexibility for the terminal adenine nucleotide unit. Theoretical NMR calculations demonstrate that the predominant solution conformation does not conform to the CCA terminus of tRNA as reported by four independent crystallographic studies of tRNAPhe. It is shown that the preferred intramolecular order of CCA in solution is such that chi 1 = chi 2 = chi 3 = 40 degrees, all the three sugars are in 3E, psi 1 = psi 2 = psi 3 = 60 degrees, phi 2 and phi 3 = 170 and 180 degrees, respectively, phi 1 = phi 2' = 205 degrees, and omega 1/omega 1 and omega 2/omega 2' = 240/205 degrees and 295/265 degrees, respectively.

Base Sequence↗
PubMed1978

Stereodynamics of dimer segments of RNA in aqueous solution.

Arguments are presented which show that conformations II and III proposed by Lee and Tinoco [Lee, C.H., and Tinoco, I., Jr. (1977), Biochemistry 16, 5403] for ribodinucleoside monophosphates in aqueous solution are untenable. It has been shown that ribodinucleoside monophosphates exist in aqueous solution as an equilibrium blend of the classically recognized right-handed stack (g-g-), loop stack (g+g+), skewed (g+t), and extended arrays. In order to determine the effect of epsilonA base on the conformer distribution in the equilibrium blend, detailed ring-current calculations were performed and the isoshielding curves for epsilonA were derived. Use of these curves vis-a-vis dimerization shift data indicates that introduction of epsilonA perturbs the equilibrium blend which causes an increase in the population of skewed (g+t) arrays.

Magnetic Resonance Spectroscopy↗
PubMed1978

Why do nucleic acids have 3'5' phosphodiester bonds?

Details of the stereochemistry of the 2'5' and 3'5' dinucleoside monophosphates of polynucleotides have been delineated in aqueous solution using nuclear magnetic resonance spectroscopy. Incorporation of these experimentally determined geometries into the structure of polynucleotides reveals that the intrinsic spatial configurations of the 2'5' bonds cannot support helical structures whereas the geometries of 3'5' bonds allow the formation of helical configurations for RNA.

Magnetic Resonance Spectroscopy↗
PubMed1978

Spatial configuration of deoxyribotrinucleoside diphosphates in aqueous solution.

The detailed conformational features and dynamics of the naturally occurring deoxyribotrinucleoside diphosphates d-TpTpT and d-TpTpC have been investigated at 20 degrees C and 80 degrees C in aqueous solution by nuclear magnetic resonance spectroscopy. The observed NMR parameters indicate that the conformational properties of the trimers are very similar to those of the constituent dimers and monomers, i.e., the monomers and dimers conserve their intrinsic conformational features when they become incorporated into oligomers. Model building indicate that the distant shieldings can originate from spatial configurations in which the central nucleotidyl unit is bulged out and the w'1w1, w'2w2 occupy /g+g+, g+g+/ domains.

Magnetic Resonance Spectroscopy↗
PubMed1977

Spatial configuration of mRNA 5'-terminus.

Nuclear magnetic resonance investigation has revealed that the 5'-terminus m7G5'ppp5'Am of mRNA displays a spatial configuration in which the bases form stacked arrays. Details of the conformation as derived from coupling constants, shift trends and ring current considerations are discussed.

Base Sequence↗
PubMed1977

Conformational properties of purine-pyrimidine and pyrimidine-purine dinucleoside monophosphates.

The detailed conformational features and dynamics of heterodinucleoside monophosphates ApU, ApC, GpU, GpC, UpA, CpA, UpG, and CpG have been studied in aqueous solution by high field nuclear magnetic resonance (NMR) spectroscopy. Analysis of the resultant NMR parameters leads to a number of discernible trends throughout the series. Thus the ribose rings of the dimers exist as equilibrium mixtures of C(2')-endo(2E) in equilibrium C(3')-endo(3E) conformers with a proclivity for the 3E pucker in most cases; the C(4')-C(5') bonds of both nucleotidyl units show significant preference (74-96%) for a gg conformation and the dominant conformer (85-89%) about C(5')-O(5') is g'g'. Orientation about the C(3')-O(3') bond is coupled to the ribose conformational equilibrium and the system exists with a bias for the 3Eg- coupled conformation in which the H(3')-C(3')-O(3')-P dihedral angle occupies the narrow range of 33-35 degrees. Dimerization, on the average, causes about 10% increase in gg and g'g' populations and the g-domain becomes increasingly populated about the C(3')-O(3') bond. The ribose equilibrium 2E in equilibrium 3E shifts in favor of 3E upon dimerization, the effect being very conspicuous for the pu-py series (similar to 40 yields 60%) and less noticeable for the py-pu systems (similar to 47 yields 58%), clearly suggesting a correlation between sequence and ribose conformational equilibrium. The temperature and dimerization data for the heterodinucleoside monophosphates show that the transition 2E yields 3E is directly related to XCN changes induced by dimerization and stacking. Analysis of the ribose coupling data shows that the percentage populations of stacked species vary from dimer to dimer with GpC displaying a maximum of 45% stacked population and UpG about 10%. However, in general, the pu-py dimers show a higher preference (27-45%) for stacked conformations than py-pu dimers (10-25%). It is proposed that the pronounced deshielding of H(5') of the 5'-nucleotidyl units upon dimerization is associated with the presence of right-handed stacks (g-g-), whereas the chemical shift trends of H(5') and H(5') of 3'-nucleotidyl units are due to the presence of left-handed stacks (g+g+) in all the dimers. In pu-py dimers, the population of the g-g- species is found to be greater than that of g+g+. Also the population of g-g- stacks in pu-py dimers is generally greater than in their corresponding matched py-pu dimers. Thus the base sequence has not only an explicit effect on the overall populations of stacked species, but also on the handedness of the stacks. The present results further confirm the interdependence of conformational bonds throughout the nucleotidyl framework.

Deuterium↗
PubMed1976

Nucleotide rigidity.

It is show that in aqueous solution the backbone conformation of adenosine is as much flexible as that of 3'-AMP, 5'-AMP and 3', 5'-ADP indicating that nucleotides are not any more rigid than nucleosides. The flexible conformation of the monomeric components is conserved in the nucleotidyl units of destacked ApA, ApApA and poly(A), but it is not conserved in base stacked conditions. The findings are extended to guanosine, uridine and cytidine systems. It is projected that in aqueous solution, conformations of the individual nucleotidyl units of yeast tRNAhe are confined to the classically stable domains in the base stacked region and non-rigid flexible structures populate in the unstacked region comprising D16, D17, G20, U47 and A76.

Adenine Nucleotides↗
PubMed1976

Conformational properties of dinucleoside monophosphates in solution: dipurines and dipyrimidines.

In order to obtain information about the conformational features in a polyribonucleotide at the nearest neighbor level, detailed nuclear magnetic resonance studies of the dinucleoside monophosphates ApA, ApG, GpA, UpU, CpC, UpC, and CpU were undertaken. Proton spectra were recorded at 100, 220, 270, or 300 MHz for D2O solutions, 0.01-0.03 M, pD 7.4 at 20+/-2 degrees C. Spectra of ApA, ApG, UpU, and UpC were also recorded in the temperature range of 70-90 degrees C. Unambiguous signal assignments of all proton resonances were made with the aid of selectively deuterated dimers. Complete, accurate sets of nuclear magnetic resonance (NMR) parameters were derived for each nucleotidyl unit by simulation-iteration methods. A complete set of chemical shift and coupling constant data was also obtained for all the constituent monomeric units at a concentration and ionization state comparable to that of the dimers. Conformational properties were evaluated quantitatively for most of the bonds in the dinucleoside monophosphates using procedures developed in earlier studies. All of the dimers have a flexible conformational framework in aqueous solution. While flexibility is allowed and alternate conformations are accessible, these molecules nevertheless attempt to achieve conformational identity by showing preferences--sometimes overwhelming preferences--for certain orientations. Thus the ribose rings exist as equilibrium mixtures of C2'-endo in equilibrium C3'-endo conformers with a bias for the C3'-endo pucker in most cases. The C4'-C5' bonds of both nucleotidyl units show significant preference (70-85%) for a gg conformation. Similarly, the dominant conformer (80-90%) about C5'-O5' is g'g'. Even though an unambiguous determination of the orientation about C3'-O3' cannot be made, there is suggestive evidence that the orientation of the 3' phosphate group is coupled to the ribose conformational equilibrium and it is likely that a 3Eg- in equilibrium 2Eg+ equilibrium exists with a bias for the 3Eg- coupled conformation in which the H3'-C3'-O3'-P dihedral angle is about 34-38 degrees. The individual nucleotidyl units in the dimers differ in several key ways from corresponding monomer conformations. Specifically, the ribose equilibrium C2'-endo in equilibrium C3'-endo shifts in favor of C3'-endo upon dimerization, the only exception being UpU. The C4'-C5' and C5'-O5' bonding network in the dimer forms a stable conformational unit and no correlation exists in the dimers between the conformational preference of this fragment and ribose conformer population. The temperature data for the dimers and dimerization data clearly indicate that the transition C2'-endo leads to C3'-endo is directly related to XCN changes brought about by dimerization and stacking...

Magnetic Resonance Spectroscopy↗
PubMed1976

Nuclear magnetic resonance studies of the solution conformation of nucleoside diphosphohexoses and their components.

The solution conformations of UDPG, UDPGN, UDPGal, UDPM, UDPGluc, UDPGalc, ADPG, ADPM, GDPG, GDPM, and CDPG and their components Glu-1-P, Gal-1-P, Man-1-P, Gluc-1-P, Galc-1-P, ADP, GDP, UDP, and CDP are studied by high resolution fast Fourier transform nuclear magnetic resonance spectroscopy with iterative computer line shape simulation. The following results were observed. (1) The six-membered ring is in 4C1 chair form with the C(5')-C(6') bond in gg equilibrium tg equilibrium for the derivatives of glucose and mannose and gt equilibrium tg for those of galactose. (2) No conformational preference can be detected for C(1')-O(1') bond in hexose-1'-P moiety. (3) Chemical shift dependencies for the pyranoid ring protons and their structural and conformational relations are: (a) axial proton is at higher field than equatorial: (b) the shielding effect of a gauche vicinal hydroxyl group is stronger than a trans vicinal; (c) the vicinity of a hydroxyl group located more than three bonds away tends to shift the proton downfield. (4) The conformation of the nucleoside 5'-diphosphate part is [anti, 2E equilibrium 3E, g'g' equilibrium g't', g'g' equilibrium g''/t''], with slight variation of each conformation occuring for individual compounds. (5) No significant interactions are detected between the hexose and nucleoside parts in the nucleoside diphosphohexoses, and the hexose and nucleoside components display the same conformational preference as they become integrated to form nucleoside diphosphohexoses.

Computers↗