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Biomedical subjects

S Arnott

Publications and source records attributed to S Arnott.

At least 55 records · Page 3Linked to original sources
PubMed1980

Visualization of an unwound DNA duplex.

Certain dyes and drugs with planar aromatic components can intercalate these into stacks of base pairs and thereby bind tightly to DNA duplexes. Intercalation at one site usually precludes intercalation between the base pairs immediately adjacent. This exclusion implies that two distinct nucleoside conformations are needed in the dinucleoside phosphates which include the intercalation site. The simplest distinction would involve no more than quantitative differences in the (usually anti) conformations at the glycosidic bonds. This could be reinforced by additional, qualitative differences in the furanose ring puckerings (C-2'-endo and C-3'-endo). For the most pronounced difference there could be qualitative differences (syn and anti) in the conformations of the glycosidic bonds as well as in the conformations of the sugar rings. The model discussed here is an example of this most emphatic distinctiveness, as the nucleosides at the 5' ends of the intercalation sites are C-3'-endo and syn and at the 3' ends are C-2'-endo and anti. X-ray diffraction analysis suggests that a completely unwound allomorph of the DNA duplex can persist in oriented fibres when stabilized by certain platinum-containing intercalators. In the untwisting of (usually) right-handed DNA double helices, unwound duplexes are presumably fleeting intermediates.

Animals↗
PubMed1980

The ribosome binding sites recognized by E. coli ribosomes have regions with signal character in both the leader and protein coding segments.

Oligonucleotide analysis, by a novel computerized procedure, was first applied to determine the sequence of an ideal E. coli promoter (Scherer et al., Nucl. Acids Res. 1978, 5:3759-3773) and has now been used to obtain the sequence of nucleotides that should be present in a messenger RNA for optimum binding to the E. coli ribosome. This sequence is: UU.UUAAAAAUUAAGGAGGUAUAUUAUGAAAAAAAUUAAAAAACUCAA AA U A AUA A CUC G. Comparison of this sequence with each of the 68 ribosome binding site sequences used to generate it shows a preference rather than an absolute requirement for a specific base in any given position. The preference for certain bases persists along the whole length of the RNA within the ribosome binding domain even though nearly half of that length includes translated codons. Thus messages without leader sequences (like lambda CI mRNA) can still have some affinity for the ribosome. Part of the model sequence is complementary to the 3'end of 16S rRNA.

Base Sequence↗
PubMed1980

Left-handed DNA helices.

The synthetic DNA polymerpoly d(GC) . poly d(GC) has been studied by X-ray diffraction of orientated fibres in which it has either the well known (A or B) randed conformations have been observed with poly d(AC) . poly d(GT) and with poly d(As4T) . poly d(As4T), demonstrating that the novel structure is accessible to any DNA segment with an alternating purine-pyrimidine base sequence.

Base Sequence↗
PubMed1979

Bent DNA: visualization of a base-paired and stacked A-B conformational junction.

A model for the junction of contiguous DNA segments having A-DNA and B-DNA conformations is generated using a computerized linked-atom, least-squares model building program. The junction region comprises one base pair and the two neighboring internucleotide linkages and exhibits full hydrogen-bonded base-pairing, full base-stacking, and unexceptional stereochemistry. In addition, the junction has a mixed sugar ring pucker with the junction base pair adopting C2-endo and C3-endo furanose sugar rings in the complementary strands. Since the junction is fully base-stacked, the differences in base tilt between A-DNA and B-DNA result in a bend of 26 degrees in the duplex at the junction. The results of this study indicate: 1) a correlation of the B leads to A transition with several features of the initiation of RNA transcription, 2) possible structural roles of alternating AT and GC sequences in protein recognition, and 3) the possibility of dynamic conformational discontinuities in a DNA helix.

Computers↗
PubMed1979

A reinterpretation of the infrared linear dichroism of oriented nucleic acid films and a calculation of some effective partial changes on the ribose phosphate backbone.

In this paper we show, based on symmetry considerations, that structural information cannot be obtained from the linear infrared dichroism of the dioxy vibrations of the phosphate group of nucleic acids. Consequently, the discrepancies between the results of x-ray structure measurements and linear dichroism measurements are not meaningful. The linear dichroism measurements are instead important for a calculation of transition dipole moments that involve both the vibrations of all the atoms of the nucleotide and their charges. Independent information on either the atomic displacements contributing to a given vibration or the atomic charges permits a refinement of the unknown quantities. Based on the molecular dynamics calculations of Prohofsky et al., atomic charges of DNA are calculated to reproduce the observed linear dichroism results. Some of the resulting charges are unexpected and may reflect the inadequacy of the molecular dynamic calculation.

DNA↗
PubMed1978

A computer aided oligonucleotide analysis provides a model sequence for RNA polymerase-promoter recognition in E.coli.

A novel computer procedure has been used to search for homology among 17 known procaryotic promoter sequences. A model sequence, :formula: (see text), is compatible with the properties of all known promoter and operator mutations, predicts base positions for the initiation of RNA synthesis coinciding with those determined experimentally, is compatible with current models for the regulation of transcription, suggests that RNA polymerase could recognize the DNA double helix firstly in the B conformation then in the A.

Base Sequence↗
PubMed1977

Stereochemical model for proflavin intercalation in A-DNA.

Linked-atom molecular modelling was employed to determine the steric and torsional requirements for intercalation of proflavine into a double-stranded region of DNA compatible with adjacent regions of cohelical A-DNA. The optimum intercalation conformation is characterized by the dihedral angles xi and psi becoming trans, with all sugars retaining the characteristics C3'-endo pucker. This extended conformation results in virtually no helical unwinding, suggesting it may be an appropriate model for an intercalative intermediary in mutagenesis by virtue of its similarity to standard helical DNA.

Acridines↗