G.U wobble base pairs are the most common and highly conserved non-Watson-Crick base pairs in RNA. Previous surface maps imply uniformly negative electrostatic potential at the major groove of G.U wobble base pairs embedded in RNA helices, suitable for entrapment of cationic ligands. In this work, we have used a Poisson-Boltzmann approach to gain a more detailed and accurate characterization of...

BACKGROUND It has been extensively developed in recent years that cell-permeable small molecules, such as polyamide, can be programmed to disrupt transcription factor-DNA interfaces and can silence aberrant gene expression. For example, cyclic pyrrole-imidazole polyamide that competes with glucocorticoid receptor (GR) for binding to glucocorticoid response elements could be expected to affect t...

The gene-specific transcription factor IIIA (TFIIIA) binds to the internal promoter element of the 5 S rRNA gene through nine zinc fingers which make specific DNA contacts. Seven of the nine TFIIIA zinc fingers participate in major groove DNA contacts while two fingers, 4 and 6, have been proposed to bind in or across the minor groove. Pyrrole-imidazole polyamides are minor groove binding ligan...

2-Amino-3-methylimidazo[4,5-f]quinolone (IQ), a heterocyclic amine found in cooked meats, undergoes bioactivation to a nitrenium ion, which alkylates guanines at both the C8-dG and N2-dG positions. The conformation of a site-specific N2-dG-IQ adduct in an oligodeoxynucleotide duplex containing the iterated CG repeat restriction site of the NarI endonuclease has been determined. The IQ moiety in...

Heat shock genes are activated by the binding of the heat shock transcription factor (HSF) to heat shock elements (HSEs), consisting of arrays of the 5-bp unit NGAAN arranged as inverted repeats. Here, we have investigated the interaction of the 5-bp unit with HSFs of Drosophila and Saccharomyces. Mutations within the conserved, central trinucleotide GAA reduce the relative binding affinity of ...

Most transcriptional regulators bind nucleotide motifs in the major groove, although some are able to recognize molecular determinants conferred by the minor groove of DNA. Here we report a transcriptional commutator switch that exploits the alternative readout of grooves to mediate opposite output regulation for the same input signal. This mechanism accounts for the ability of the Helicobacter...

Grooved terrain is subdivided on the basis of pervasive morphology into (!) groove lanes elongate parallel groove bands, (2) grooved polygons polygonal domains ofparallel grooves, (3) reticulate rrain polygonal domains of orthogonal grooves, and (4) complex grooved terrain polygons with several complexly cross-cutting groove sets. Detailed geologic mapping ofselect areas, employing previously e...

In this paper, an analytical formula to calculate the radial stiffness of groove elastic support is presented. The influence of structure parameters on radial stiffness and homogeneity of radial stiffness is investigated as well. The accuracy and calculating speed of the analysis formula are compared to that of finite element method (FEM). Findings are as following: The calculating speed of ana...

Many human diseases are caused by dysregulated gene expression. The oversupply of transcription factors may be required for the growth and metastatic behavior of human cancers. Cell permeable small molecules that can be programmed to disrupt transcription factor-DNA interfaces could silence aberrant gene expression pathways. Pyrrole-imidazole polyamides are DNA minor-groove binding molecules th...