DNA Structure and Stability

DNA Structure and Stability

• The cumulative effect of weak van der Waals contacts between individual stacked base pairs contributes to the stability of large DNA molecules.
• Electrostatic interactions between negatively charged phosphate groups in the sugar-phosphate backbone are minimized by the shielding effects of divalent cations and polycationic molecules.

DNA Base Pair Stacking

• In B-DNA, base pairs are stacked one above the other, nearly perpendicular to the long axis of the molecule.
• Cooperative, non-covalent interactions between the upper and lower surfaces of each base pair bring the pairs closer together, creating a hydrophobic interior.
• This stacking interaction creates the familiar double helix structure.

The Double Helix Structure

• The sugar-phosphate backbone winds around the outside of the helix, exposed to the aqueous environment.
• The stacked, relatively hydrophobic bases are located in the interior of the helix, shielded from water.
• The double helix has two grooves of unequal width, the major groove and the minor groove, due to the way base pairs stack and the sugar-phosphate backbones twist.

Base Pairing and Grooves

• Functional groups on the edges of the base pairs are exposed to water and are chemically distinguishable within the grooves.
• The base pairs are accessible in the grooves, allowing molecules to interact with specific base pairs without disrupting the helix.

Dimensions of Crystalline DNA

• One turn of the double helix spans 3.4 nm and consists of approximately 10.4 base pairs.
• The diameter of the double helix is 2.4 nm.
• The interior space of the double helix is only suitable for base pairing a purine and a pyrimidine.
• The distance between adjacent base pairs is 0.34 nm.

Non-Covalent Bonding Interactions

• Hydrophobic interactions between stacked purine and pyrimidine bases contribute to the stability of the DNA structure.
• Hydrogen bonds form between base pairs, with three between GC pairs and two between AT pairs.
• Base stacking interactions also contribute to the stability of the DNA structure.

Watson-Crick Model

• The Watson-Crick model accounts for the equal amounts of purines and pyrimidines by proposing a double-stranded DNA with specific base pairing.
• The model suggests that DNA consists of two polynucleotide strands wound around each other to form a right-handed double helix.

Base Composition of DNA

• The base composition of DNA can vary between organisms, with different ratios of purines to pyrimidines.
• Table 1 shows the base composition of DNA in various organisms, including E. coli, M. tuberculosis, yeast, cow, pig, and human.

Nucleotides and Phosphodiester Linkages

• A tetra-nucleotide can be referred to as 5' pApGpTpC 3', or even AGTC
• Phosphate groups have a pKa of about 2 and bear a negative charge at neutral pH
• Nucleic acids are polyanions under physiological conditions

Double-Stranded (ds) DNA Structure

• Erwin Chargaff observed that in DNA, A and T are present in equimolar amounts, as are G and C
• The percentage of purine bases always equals the percentage of pyrimidine bases in DNA
• The ratio of purines to pyrimidines in DNA is always 1:1
• The DNA of some organisms, such as yeast, is relatively deficient in G+C, whereas the DNA of other organisms, such as Mycobacterium tuberculosis, is rich in G+C
• The DNAs of closely related species, such as cows, pigs, and humans, have similar base compositions
• Guanine (a purine) pairs with cytosine (a pyrimidine)
• One turn of the double helix spans 3.4 nm and consists of approximately 10.4 base pairs
• The diameter of the double helix is 2.4 nm
• The distance between adjacent base pairs is 0.34 nm
• The two strands run in opposite directions, and the order of bases in one strand determines the sequence of bases of the other strand

Forces Stabilizing DNA Structure

• Hydrophobic interactions between stacked purine and pyrimidine bases
• Hydrogen bonds between base pairs (3 between GC pairs and 2 between AT pairs)
• Base stacking interactions between stacked base pairs
• Electrostatic interactions between negatively charged phosphate groups and divalent cations

B-DNA Structure

• Base pairs are stacked one above the other and are nearly perpendicular to the long axis of the molecule
• The cooperative, non-covalent interactions between the upper and lower surfaces of each base pair bring the pairs closer together
• The stacking interactions create a hydrophobic interior that causes the sugar-phosphate backbone to twist
• The double helix has two grooves of unequal width, the major groove and the minor groove

Single-Stranded (ss) DNA Structure

• Nucleotides are the building blocks of DNA
• Each nucleotide monomer in DNA is composed of a nitrogenous base, a deoxyribose sugar, and phosphate
• Nucleotides are linked to each other by 3' to 5' phosphodiester bonds
• The primary structure of a nucleic acid is the sequence of residues connected by 3', 5'-phosphodiester bonds linkages