Helix stacking

The interstrand cross-link also induces DNA bending.72 X-ray and NMR studies on this adduct show that platinum is located in the minor groove and the cytosines of the d(GC) base pair involved in interstrand cross-link formation are flipped out of the helix stack and a localized Z-form DNA is observed.83-85 This is a highly unusual structure and very distorting—implications for differential repair of the two adducts have been addressed. Alternatively, the interstrand cross-link of the antitumor inactive trans-DDP is formed between a guanine (G) and its complementary cytosine (C) on the same base p a i r.86,87/ nms- D D P is sterically incapable of producing 1,2-intrastrand adducts and this feature has been cited as a dominant structural reason for its lack of antitumor efficacy. It is clear that the structural distortions induced on the DNA are very different and likely to induce distinctly different biological consequences. 

Figure 29.6. Helix Stacking in tRNA. The four helices of the secondary structure of tRNA (see Figure 29,4) stack to form an L-shaped structure.

Despite an impressive progress in detailed physical understanding of the DNA melting phenomenon, the central question on the nature of forces determining the stability of the double helix remained unanswered until very recently. Indeed, there are two radically different interactions within the double helix stacking between adjacent base pairs and pairing between complemen-... 

The unmodified and complementary oligonucleotides were also synthesized, in order to detect thermodynamic and spectroscopic differences between the double helices. Circular dichroism spectra revealed that the covalently bound anthracene does not stack in the centre of the DNA double helix. Mutagenic activity by intercalative binding of the anthracene residue is thus unlikely. Only in vitro and in vivo replication experiments with site-specifically modified... 

The helix can be viewed as a stacked array of pepdde planes hinged at the (X-carbons and approximately parallel to die helix. 

Figure 12.16), can insert between the stacked base pairs of DNA. The bases are forced apart to accommodate these so-called intercalating agents, causing an unwinding of the helix to a more ladderlike structure. The deoxyribose-phosphate backbone is almost fully extended as successive base pairs are displaced 0.7 nm from one another, and the rotational angle about the helix axis between adjacent base pairs is reduced from 36° to 10°. 

Binding of cisplatin to the neighbouring bases in the DNA disrupts the orderly stacking of the purine bases when it forms a 1,2-intrastrand crosslink, it bends the DNA helix by some 34° towards the major groove and unwinds the helix by 13°. These cross-links are believed to block DNA replication. 

Fig. 11 Phase diagram of a twisted ribbon solution that forms fibrils. The axes represent relative helix pitch of isolated ribbons and relative stacking attraction of ribbons. Reproduced from Aggeli et al. [20]. Copyright 2001 National Academy of Sciences, USA...

The DNA double heUx illustrates the contribution of multiple forces to the structure of biomolecules. While each individual DNA strand is held together by covalent bonds, the two strands of the helix are held together exclusively by noncovalent interactions. These noncovalent interactions include hydrogen bonds between nucleotide bases (Watson-Crick base pairing) and van der Waals interactions between the stacked purine and pyrimidine bases. The hehx presents the charged phosphate groups and polar ribose sugars of... 

The nucleotide bases are flat molecules. Each base pair is parallel to the one below it, with 340 picometers separating the two. There is a rotation of 36° between pairs, giving ten base pairs per complete turn of the helix. The two sugar-phosphate backbone strands wind around these stacked pairs, as shown in Figure 13-29. The two strands of DNA run in opposite directions, with the terminal phosphate end of one polynucleotide matched with the free hydroxyl end of the other. 

Structural analysis of the two pectate lyases PelC and PelE (5, 6), demonstrated that these proteins fold in a large heHx of parallel P strands. A stack of asparagine residues parallel to the helix probably plays a role in the stabUity of this structure. Identification of the structurally conserved amino adds lead to a reaHgnment of the protein sequences (7). In addition to Erwinia extracellular pectate lyases, the multiple aHgnment indudes the Bacillus subtilis pectate lyase, Aspergillus tdger and E. carotovora pectin lyases and plant proteins. 

C2 Z = 4 Dx = 1.41 R = 0.102 for 4,115 intensities. The structure is a 3 2 complex of proflavine and CpG. The asymmetrical unit contains one CpG molecule, 1.5 proflavine molecules, 0.5 sulfate ion, and 11 5 water molecules. Two CpG molecules form an antiparallel, Watson-Crick, miniature duplex, with a proflavine intercalated between the base pairs through the wide groove. The double helix has exact (crystallographic), two-fold symmetry, and the crystallographic, two-fold axis passes through the C-9-N-10 vector of the intercalated proflavine. A second and a third molecule of proflavine are stacked on top of the C - G pairs ... 

The central role played by DNA in cellular life guarantees a place of importance for the study of its chemical and physical properties. It did not take long after Watson and Crick described the now iconic double helix structure for a question to arise about the ability of DNA to transport electrical charge. It seemed apparent to the trained eye of the chemist or physicist that the array of neatly stacked aromatic bases might facilitate the movement of an electron (or hole) along the length of the polymer. It is now more than 40 years since the first experimental results were reported, and that question has been answered with certainty. 

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