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Biomedical subjects

J Kypr

Publications and source records attributed to J Kypr.

At least 91 records · Page 5Linked to original sources

Different behavior of the octadeoxynucleotides d(A-T)4 and d(T-A)4 at high concentrations of cesium fluoride.

High CsF concentrations induce a zig-zag double helix, which we call X-DNA, in poly d(A-T) and also in the octadeoxynucleotide d(T-A)4 while d(A-T)4 remains fixed in a B-DNA form. Intermolecular contacts promote the B-X isomerization of the former oligonucleotide but induce aggregation of the latter. This indicates that there is an intramolecular factor, presumably base stacking in the T-A steps, stabilizing the X-DNA conformation.

Cesium↗

Lambda phage protein Nu 1 contains the conserved DNA binding fold of repressors.

Analysis of 64 lambda phage proteins revealed the presence of four strong variants of the conserved DNA binding fold of repressors. Three of them have been known from previous studies but the Nu 1 gene product is a new member of the family of proteins that may bind strongly to DNA in the repressor-like fashion. It is peculiar that the motif occurs in the very N terminus of Nu 1 just between two possible starts of its gene.

Amino Acid Sequence↗

NMR relaxation and the structure of a synthetic DNA poly(dA-dT).poly(dA-dT).

1H-1H and 31P-1H nuclear Overhauser effects and 31P NMR spin-lattice relaxation times were measured for a synthetic DNA poly(dA-dT).poly(dA-dT) in a low-salt aqueous solution. The results have shown that all bases in the double helix are anti-orientated with respect to deoxyribose residues and that the sugar-phosphate backbone has an alternating architecture.

Base Sequence↗

Graphical analysis of circular dichroic spectra distinguishes between two-state and gradual alterations in DNA conformation.

A simple graphical method is proposed to distinguish between two-state and gradual alterations in DNA conformation from circular dichroic spectra. The method is advantageous particularly to identify two-state conformational isomerizations which exhibit low degree of cooperativity. The usefulness of the method is illustrated on the examples of two synthetic DNA molecules which isomerize due to temperature changes or changes in salt concentration. The method can be used to characterize any phenomenon accompanied by alterations in optical activity.

Circular Dichroism↗

RNA-like conformational properties of a synthetic DNA poly(dA-dU).poly(dA-dU).

Differences in the circular dichroism of poly(dA-dT).poly(dA-dT) and poly(dA-dU).poly(dA-dU) and in its temperature induced changes are reported. A comparison to the data obtained with DNA and RNA indicates that an absence of thymine methyl groups in the polynucleotide results in promoting its RNA-like conformational properties. However, poly(dA-dU).poly(dA-dU) is not an A-DNA type of double helix.

Animals↗

Possible mechanism of the allosteric activation of cAMP receptor protein.

Secondary structure of cAMP receptor protein of E. coli was predicted and compared to its crystal structure in the complex with cAMP solved by McKay and Steitz. The two conformations coincide in the DNA binding domain but strikingly differ in the other domain which binds cAMP and causes protein dimerization. The comparison indicates that cAMP destabilizes a very long helix instead of which sheets are formed creating a hydrophobic pocket where cAMP binds. Consequently, the helix-sheets isomerization and a resulting change in the relative monomer disposition in the dimer appears to be the origin of cAMP-induced allosteric activation of the protein. Extremely long helices were also predicted in the regions of the regulatory subunit of cAMP-dependent protein kinase from bovine cardiac muscle where cAMP binds. It is thus likely that the proposed mechanism of the effect of cAMP on protein structure has wider implications.

Allosteric Regulation↗

Sequence-dependent changes in the chiroptical properties of DNA upon interaction with dipyrandium.

Interaction of dipyrandium with DNA and its dependence on the base sequence was studied using circular dichroism. It was found that calf thymus DNA and polynucleotide duplexes with alternating purine-pyrimidine sequences containing GC basepairs underwent similar alterations in the chiroptical properties upon binding of dipyrandium. The alterations suggest that these DNAs have similar B-type structures which may kink at the dipyrandium binding sites. On the other hand, poly(dA-dT).poly(dA-dT) and especially poly(dA-dU).poly(dA-dU) exhibit some features of A-type structure. Poly(dA-dT).poly(dA-dT) changes its chiroptical properties little when complexed with dipyrandium, as if it contained some type of kinks as equilibrium structural elements.

Animals↗

Conformations of alternating purine-pyrimidine DNAs in high-CsF solutions and their reversal by dipyrandium, ethidium and high temperature.

Chiroptical properties of synthetic DNAs with alternating purine-pyrimidine sequences were studied in high-CsF solutions. It was found that this salt transformed all the DNAs to non-canonical conformations like Z or X, which show striking negative bands in the long wavelength part of the CD spectra. The negative bands were reversed upon interaction with dipyrandium, ethidium and at high temperature.

Animals↗

Conformational variability of poly(dA-dT).poly(dA-dT) and some other deoxyribonucleic acids includes a novel type of double helix.

The article reviews data indicating that poly(dA-dT).poly(dA-dT) is able of adopting three distinct double helical structures in solution, of which only the A form conforms to classical notions. The other two structures have dinucleotides as double helical repeats. At low salt concentrations poly(dA-dT).poly(dA-dT) adopts a B-type alternating conformation which is exceptionally variable. Its architecture can gradually move in the limits demarcated by the CD spectra with inverted long wavelength CD bands and the 31P NMR spectra with a very low and a 0.6 ppm separation of two resonances. Contrary to Z-DNA, the 31P NMR spectrum of the limiting alternating B conformation of poly(dA-dT).poly(dA-dT) is characterized by an upfield shift of one resonance. We attribute the exceptional conformational flexibility of the alternating B conformation to the unequal tendency of bases in the dA-dT and dT-dA steps to stack. However, by assuming the limiting alternating B conformation, the variability of the synthetic DNA is not exhausted. Specific agents make it isomerize into another conformation by a fast, two-state mechanism, which is reflected by a further deepening of the negative long wavelength CD band and a downfield shift of the 31P NMR resonance of poly(dA-dT).poly(dA-dT) that was constant in the course of the gradual alterations of the alternating B conformation. These changes are, however, qualitatively different from the way poly(dG-dC).poly(dG-dC) behaves in the course of the B-Z isomerization. Poly(dG-dC).poly(dG-dC) displays purine-pyrimidine (dGpdC) resonance in the characteristic downfield position, while the downfield resonance of poly(dA-dT).poly(dA-dT) belongs to the pyrimidine-purine (dTpdA) phosphodiester linkages. Consequently, phosphodiester linkages in the purine-pyrimidine steps play a similar role in the appearance of the Z form to the pyrimidine-purine phosphodiesters in the course of the isomerization of poly(dA-dT).poly(dA-dT). This excludes that the high-salt structures of poly(dA-dT).poly(dA-dT) and poly(dG-dC).poly(dG-dC) are members of the same conformational family. We call the high-salt conformation of poly(dA-dT).poly(dA-dT) X-DNA. It furthermore follows from the review that synthetic molecules of DNA with alternating purine-pyrimidine sequences of bases can adopt either the Z form or the X form, or even both, depending on the environmental conditions. This introduces a new dimension into the DNA double helix conformational variability. The possible biological relevance of the X form is suggested by experiments with linear molecules of natural DNA.(ABSTRACT TRUNCATED AT 400 WORDS)

Cesium↗

Experiment acknowledged the Watson-Crick hypothesis: a review of B-DNA double helix structural features at atomic resolution.

The dodecamer d(CGCGAATTCGCG) forms a right-handed B-DNA double helix of a Watson-Crick type both in crystal and solution. It is the first piece of DNA longer than one helix turn whose molecular structure has become known at the atomic resolution. The article reviews qualitative aspects of its structure with a special emphasis on local variations in the disposition of base pairs in the double helix.

Cisplatin↗

Thermal melting of poly(dA-dT).poly(dA-dT) in methanol-water solutions.

Thermal melting of a synthetic DNA poly(dA-dT).poly(dA-dT) was investigated in methanol-water solutions. Methanol decreased melting temperature of the polynucleotide but the decrease was qualitatively different in the presence of milimolar concentrations of sodium and cesium cations. The difference is a consequence of the fact that poly(dA-dT).poly(dA-dT) undergoes a helix-helix conformational isomerization in methanol-water solutions which is cesium cation specific. The arising conformation is much more stable than the conformation which poly(dA-dT).poly(dA-dT) adopts in solutions with sodium cations at high methanol concentrations. The (A+T) rich DNA of Bacillus cereus displays a similar behaviour.

Hot Temperature↗

Salt and base sequence specific changes in the chiroptical properties of DNA.

Chiroptical properties of natural DNA molecules differing in base composition were studied in solutions with high concentrations of monovalent sodium and caesium salts. It was found that the properties were dependent on the DNA base sequence and nature of both cations and anions. A comparison with the behaviour of the synthetic molecules of DNA demonstrated that the salt-induced changes in the natural molecules of DNA could not be accounted for by the appearance of the left-handed Z conformation. On the other hand, the tendency of the alternating A--T sequence to assume the novel X--DNA conformation seems to play a role even in the conformational properties of natural DNA.

Animals↗

Salt-induced conformational transition of poly[d(A-T)] X poly[d(A-T)].

Unique chiroptical properties of poly[d(A-T)] X poly[d(A-T)] observed in CsF solutions (Vorlícková et al., 1980) were specified by circular dichroism, ultraviolet light and 31P nuclear magnetic resonance spectroscopy. It was found that up to a 3 M concentration of the salt, caesium cations induced a gradual rearrangement of the polynucleotide double helix during which the phosphodiester bonds in one sequence changed the geometry and the base stacking decreased. At higher CsF concentrations poly[d(A-T)] X poly[d(A-T)] underwent a transition toward a novel conformation which had phosphodiester bonds in both sequences in considerably different non-B-DNA geometries.

Cesium↗

Conformational transitions of poly(dA-dT)poly(dA-dT) in ethanolic solutions.

Examination of circular dichroic and phosphorus nuclear magnetic resonance spectra showed that poly(dA-dT)-poly(dA-dT) exhibited an ethanol-induced transition to the A form in an Na+ containing medium like natural DNAs. A mere replacement of the Na+ by Cs+ counterions meant that the polynucleotide was with a little cooperativity transformed into a novel conformation displaying a deep negative band in the long wavelength part of the CD spectrum. The presence of very low concentration of Cs2+ shifted the midpoint of the transition to a lower content of ethanol.

Circular Dichroism↗