New insights into DNA triplexes: residual twist and radial difference as measures of base triplet non-isomorphism and their implication to sequence-dependent non-uniform DNA triplex

DNA triplexes are formed by both isomorphic (structurally alike) and non-isomorphic (structurally dissimilar) base triplets. It is espoused here that (i) the base triplet non-isomorphism may be articulated in structural terms by a residual twist (Δt°), the angle formed by line joining the C1′…C1′ atoms of the adjacent Hoogsteen or reverse Hoogsteen (RH) base pairs and the difference in base triplet radius (Δr Å), and (ii) their influence on DNA triplex is largely mechanistic, leading to the prediction of a high (t + Δt)° and low (t − Δt)° twist at the successive steps of Hoogsteen or RH duplex of a parallel or antiparallel triplex. Efficacy of this concept is corroborated by molecular dynamics (MD) simulation of an antiparallel DNA triplex comprising alternating non-isomorphic G*GC and T*AT triplets. Conformational changes necessitated by base triplet non-isomorphism are found to induce an alternating (i) high anti and anti glycosyl and (ii) BII and an unusual BIII conformation resulting in a zigzag backbone for the RH strand. Thus, base triplet non-isomorphism causes DNA triplexes into exhibiting sequence-dependent non-uniform conformation. Such structural variations may be relevant in deciphering the specificity of interaction with DNA triplex binding proteins. Seemingly then, residual twist (Δt°) and radial difference (Δr Å) suffice as indices to define and monitor the effect of base triplet non-isomorphism in nucleic acid triplexes

E. coli Group 1 Capsular Polysaccharide Exportation Nanomachinary as a Plausible Antivirulence Targetin the Perspective of Emerging Antimicrobial Resistance

Bacteria evolving resistance against the action of multiple drugs and its ability to disseminate the multidrug resistance trait(s) across various strains of the same bacteria or different bacterial species impose serious threat to public health. Evolution of such multidrug resistance is due to the fact that, most of the antibiotics target bacterial survival mechanisms which exert selective pressure on the bacteria and aids them to escape from the action of antibiotics. Nonetheless, targeting bacterial virulence strategies such as bacterial surface associated polysaccharides biosynthesis and their surface accumulation mechanisms may be an attractive strategy, as they impose less selective pressure on the bacteria. Capsular polysaccharide (CPS) or K-antigen that is located on the bacterial surface armors bacteria from host immune response. Thus, unencapsulating bacteria would be a good strategy for drug design, besides CPS itself being a good vaccine target, by interfering with CPS biosynthesis and surface assembly pathway. Gram-negative Escherichia coli uses Wzy-polymerase dependent (Groups 1 and 4) and ATP dependent (Groups 1 and 3) pathways for CPS production. Considering E. coli as a case in point, this review explains the structure and functional roles of proteins involved in Group 1 Wzy dependent CPS biosynthesis, surface expression and anchorage in relevance to drug and vaccine developments

Variation of conformational angles ɛ(C3′–O3′), ζ(O3′–P) and χ(C1′–N9/N1) and P (phase angle of pseudo rotation) in the central 10mer of the RH strand over 4 ns dynamics

<p><b>Copyright information:</b></p><p>Taken from "New insights into DNA triplexes: residual twist and radial difference as measures of base triplet non-isomorphism and their implication to sequence-dependent non-uniform DNA triplex"</p><p>Nucleic Acids Research 2005;33(1):43-55.</p><p>Published online 18 Jan 2005</p><p>PMCID:PMC546132.</p><p>© 2005, the authors © </p> Alternating (G) and (T) glycosyl conformation along with alternating BII (GT step) and BIII (TG step) conformation may be seen

Schematic diagram showing the water network around the tetrameric triplex TAT–GGC–TAT–GGC

<p><b>Copyright information:</b></p><p>Taken from "New insights into DNA triplexes: residual twist and radial difference as measures of base triplet non-isomorphism and their implication to sequence-dependent non-uniform DNA triplex"</p><p>Nucleic Acids Research 2005;33(1):43-55.</p><p>Published online 18 Jan 2005</p><p>PMCID:PMC546132.</p><p>© 2005, the authors © </p> Donor…acceptor distances within 3.5 Å are shown by dotted lines. Filled circles (grey) indicate water molecules

Variation of N3(T)…N7(A) and O2(T)…N6(A) RH hydrogen bond distances over 4 ns simulation

<p><b>Copyright information:</b></p><p>Taken from "New insights into DNA triplexes: residual twist and radial difference as measures of base triplet non-isomorphism and their implication to sequence-dependent non-uniform DNA triplex"</p><p>Nucleic Acids Research 2005;33(1):43-55.</p><p>Published online 18 Jan 2005</p><p>PMCID:PMC546132.</p><p>© 2005, the authors © </p> Note the large fluctuation in N3(T)…N7(A) hydrogen bond distance during the first 400 ps, and in O2(T)…N6(A) hydrogen bond distance during the first 1600 ps. These are correlated with water-mediated interactions shown in (see also text). Hydrogen bond distances at every 1 ps interval are calculated