Search PubMed⌕ Search

Biomedical subjects

V B Zhurkin

Publications and source records attributed to V B Zhurkin.

45 records · Page 3Linked to original sources
PubMedDate not supplied

[The effect of temperature and ionic strength on the electrophoretic motility of synthetic DNA fragments].

The following DNA fragments were studied: T5A5, U5G5, C5G5, RI (CCGAATTCGG), and RV (CCGATATCGG). The ligated decamers were run on 8% polyacrylamide gel. The PAGE anomaly was measured by the R-factor. Under standard conditions R is maximum for A5G5 and U5A5 (R = 1.9-2.0); R has intermediate values for RI and T5A5 (R200 = 1.05-1.10). T5A5 exhibits unusual non-monotonous temperature dependence of the R-factor, which reaches its maximum at 35 degrees C. Based on this fact we make two conclusions: (i) PAGE anomaly is highly sensitive to the DNA winding angle tau, (ii) tau = 36 degrees for T5A5 under these conditions. For A5G5, RI and RV the temperature dependence of the R-factor is conventional: R monotonously decreases. Conceivably tau less than 36 degrees for these sequences. In the presence of 10 mM of MgCl2 the anomaly increase for all fragments, except for T5A5; e.g. for C5G5R150 R200 = 1.2. This testifies to the moderate curvature of C5G5. The results of the measurements were interpreted on the basis of the wedge AA and junction An/B models. To get a better agreement with the experiment these models should be supplemented with the bends in the YR dimers (TA, CG, CA) directed into the major groove and with the bends in AT directed into the minor groove.

Base Sequence↗
PubMedDate not supplied

[S-N transition of the saccharide ring in B-form DNA].

A conformational transition of a single deoxyribose was analyzed in B-form trimers dA3:dT3 and dG3:dC3, both in the purine and pyrimidine chains. The main results were obtained for the duplexes with frozen ends, which could be extended by regular double helixes. The geometry of the central sugar ring in the duplexes may strongly deviate from the regular conformation. When deoxyribose changed its conformation in the central pyrimidine, the energy increase was proved to be less significant in comparison with that for purine. In the case of Thy, a decrease in pseudorotation angle P from 140 to 80 degrees causes the energy increase of 0.5 kcal/mol only, the barrier being 1.2 kcal/mol. The energy profile for Cyt has several local minima. The results of calculations were compared with numerous experimental data, they help to explain some NMR data. A perturbation of the duplex AAA:TTT structure caused by the thymine sugar ring transition, produces 5 degrees bend of the DNA axis directed toward adenines. We also investigated the influence of such conformational disturbance on the neighbouring base pairs, in particular the transition in the trimers with unfrozen ends.

DNA↗
PubMedDate not supplied

[Eight types of stacking interaction in dinucleotides. Conformational analysis of ApA, ApC, CpA, CpC, GpG].

On the basis of general stereochemical considerations the classification of the stacking state of dinucleoside phosphate (DNP) including eight types of stacks of nucleic bases has been suggested. With the use of the algorithm, which makes possible determination of the backbone conformation for the given nucleic bases arrangement, the stacking conformes of DNP were analysed by atom-atom potential method. For all compounds different types of stacking conformes were obtained with energy values lower than that for the unstacking state. It follows from the results of calculations that for description of the conformational situation of DNP in solution the "non-canonical" conformers should be born in mind. In particular the forms having different sugar conformations in Np- and in pN-parts of the dimers are of interest. The effect of choice of the atom-atom potential functions on optimal conformation of DNP is discussed. For single-stranded RNA several regular and non-regular structures are proposed.

Adenine Nucleotides↗
PubMedDate not supplied

[Anisotropic flexibility of DNA depends on the base sequence. Conformation calculations of double-stranded tetranucleotides AAAA:TTTT, (AATT)2, (TTAA)2, GGGG:CCCC, (GGCC)2, (CCGG)2].

The bending flexibility of six tetramers was studied in an assumption that they were extended in the both directions by regular double helices. The bends of B-DNA in different directions were considered. The stiffness of the B-DNA double helix when bent into the both grooves proved to be less pronounced than in the perpendicular direction by the order of magnitude. Such an anisotropy is a feature of the sugar-phosphate backbone structure. The calculated fluctuations of the DNA bending along the dyad axis, 5-7 degrees, are in agreement with the experimental value of DNA persistence length. Anisotropy of the double helix is sequence-dependent: most easily bent into the minor groove are the tetramers with purine-pyrimidine dimer (RY) in the middle. In contrast, YR dinucleotides prefer bending into the major groove, moreover, they have an equilibrium bend of 6-12 degrees into this groove. The above inequality is caused by the stacking interaction of the bases. The bend in the central dimers is distributed to some extent between the adjacent links, though the main fraction of the bend remains within the central link. Variation of the sugar-phosphate geometry in the bent helix is unessential, so that DNA remains within the limits of the B-family of forms: namely, when the helical axis is bent by 20 degrees the backbone dihedral angles vary by no more than 15 degrees. The obtained results are in accord with the X-ray structure of B-DNA dodecamer; they further substantiate our earlier model of DNA wrapping in the nucleosome by means of "mini-kinks" separated by a half-pitch of the double helix, i.e. by 5-6 b. p. Sequence-dependent anisotropy of DNA presumably dictates the three-dimensional structure of DNA in solution as well. We have found that nonrandom allocation of YR dimers leads to the systematic bends in the equilibrium structure of certain DNA fragments. To the four "Calladine rules" two more can be added: the minor-groove steric clash of purines in the YR sequences are avoided by: (1) bending of the helix into the major groove; (2) increasing the distance between the base pairs (stretching the double helix).

Base Sequence↗
PubMedDate not supplied

[Local mobility of the DNA double helix. Comparison of conformational analysis with experiments].

The conformational studies of the torsional, tensile and bending flexibility of DNA within the B-family of forms are reviewed. The calculated values are in agreement with the experimental data. It means that the basic mechanism of the double helix elasticity descends from the small amplitude torsional vibrations of atoms. The torsional flexibility of B-DNA depends on the nucleotide sequence, namely poly(dA) . poly(dT) is stiffer than poly(dG) . poly(dC) due to the interactions between methyl groups of thymines and (C2(1) H2-groups of the neighbouring sugar rings. It is found that the B leads to A transition increases the torsional stiffness of the double helix as well. Possible correlation between conformational changes in the adjacent nucleotides is discussed. The crystalline structure of the dodecamer CGCGAATTCGCG testifies to the anisotropic flexibility of DNA and confirms the model for DNA folding in the nucleosome by virtue of "mini-kinks". The bending stiffness of DNA presumably depends on the base sequence: purine-pyrimidine dimers prefer bending into the minor groove, while pyrimidine-purine dinucleotides are more easily bent into the major one. Fluctuations in B-DNA are compared with those in alpha-helix.

DNA↗
PubMedDate not supplied

[Study of the flexibility of complementary dinucleoside phosphates by the Monte-Carlo method].

Monte-Carlo calculations have revealed a significant flexibility of the double stranded dinucleoside phosphates AA: TT, AT: AT, TA: TA, GG: CC, GC: GC and CG: CG within the limits of the B-family of forms. Fluctuations of the dihedral angles and of the phase angle of pseudorotation, P, have been found to be 5-20 degrees and 10-20 degrees respectively. The r.m.s. deviation of the helical winding angle varies from 3 degrees to 6 degrees for different dimers. The G: C-containing dimers proved to be more rigid that the A: T-containing ones, though the methyl groups of thymines take part in stabilization of AA: TT and AT: AT dimers. The propeller angles in A: T and G: C pairs are of opposite sing. The pyrimidine-(3'-5')-purine dinucleoside phosphates demonstrate the least stability. All the dimers proved to be more flexible when opened into both grooves than in perpendicular directions. Due to the greater value of the glycosidic angle in the 3'-monomer the base pairs are opened into the wide groove. A connection between opening of the base pairs and bending of the double helix for different nucleotide sequences has been discussed. This might be important for the DNA package in nucleosomes.

Base Composition↗
PubMedDate not supplied

[Conformational possibilities of the regular single-stranded polyribonucleotides].

It was shown that in case of C(3')-endo pucker of ribose two left and two right types of helices are possible from the energetical point of view. However, such helices with C(2')-endo conformation of ribose are extremely unfavourable due to the steric hindrance caused by 2'-OH group. In this case the low energy structures have bases outside and phosphate groups inside the helix. The right and the left poly(A) helices have similar energy values, the barrier of transition between them being rather small. Biregular structures, i.e. the helices on which dinucleotide serves as the repeating unit, were also considered. These forms proved to be energetically optimal in the case of poly(A-C).

Models, Molecular↗