DNA Structure and Nucleotide Composition

• DNA serves as the store and transmitter of genetic information.
• In 1953, James Watson and Francis Crick introduced a DNA structure, following Rosalind Franklin's X-ray diffraction image of DNA in 1952.
• A nucleotide is the basic structural unit of DNA.

Nucleotide Composition

• Deoxyribose a pentose sugar, is esterified with a phosphate group at the 5' position and a nitrogenous base at the 1' site.
• Phosphate group - a component of nucleotides
• Nitrogenous bases are purines and pyrimidines.
• Nucleotides link covalently to form a strand with a sugar and phosphate backbone, connected by 3'-5' phosphodiester bonds.

Pyrimidines

• Pyrimidines feature a single-ring structure.
• Thymine (T) and Cytosine (C) are the two pyrimidines in DNA.

Purines

• Purines feature a double-ring structure.
• Guanine (G) and Adenine (A) are the two purines present in DNA.

Watson-Crick DNA Model

• Two nucleotide chains compose the DNA molecule
• The two chains form a pair of right-handed helices as they spiral around each other.
• The two chains in a double helix run in opposite, antiparallel directions aligned 5' to 3' and 3' to 5'.
• Sugar and phosphate form the backbone on the outside, with nitrogenous bases projecting inward.
• The phosphate groups render a large negative charge to the molecule.
• Bases stack perpendicularly to the molecule's long axis, resembling a pile of plates.
• The stability of the DNA molecule is enhanced by hydrophobic interactions and van der Waals forces between stacked bases.
• Hydrogen bonds hold together the nitrogenous bases of antiparallel polynucleotide strands.
  • Adenine (A) pairs with Thymine (T) via two hydrogen bonds.
  • Guanine (G) pairs with Cytosine (C) via three hydrogen bonds, they provide the only attractive forces in the double helix.
• The distance from the phosphate backbone to the axis center is 1 nm, resulting in a 2 nm double helix width.
• A pyrimidine always pairs with a purine, maintaining a uniform molecule width of 2 nm.
• Grooves form between helix turns and are of two types: major (wider) and minor (narrower), spiraling the double helix's outer surface.
  • Protein domains can fit into these grooves, allowing proteins to read nucleotide sequences.
• The double helix has one complete turn every 10 residues being 3.4 nm, or 150 turns per million daltons in molecular mass.
• Base pairs are spaced 10 Å apart. Double helix diameter: 20 Å.
• A always bonds with T, and G always bonds with C. Nucleotide sequences are fixed relative to each other on the two strands.
• The two DNA chains are complementary: A is complementary to T, 5'-AGC-3' is complementary to 3'-TCG-5', and one entire chain is complementary to the other.

Chargaff's Rule

• Regardless of origin, the amounts of purine and pyrimidine components are equal in a DNA molecule.
• The amount of A is the same as T, and the amount of G is the same as C.
• The A=T/G≡C base ratio can vary between animal groups but generally stays constant within a species.

Variations in DNA Forms

• B-DNA, or B-form DNA, refers to the classic Watson-Crick model.
• A-DNA, Z-DNA, CDNA, D-DNA, and E-DNA are the different forms of DNA that can appear under certain conditions.
• The diversity in structure depends on the:
  • Number of base pairs per turn in the DNA helix.
  • Pitch or angle between each base pair.
  • Helical diameter of the molecule.
  • Handedness of the double helix.

DNA Forms

• B-DNA is the most common form, derived from X-ray diffraction of sodium salt DNA fibers at 92% relative humidity.
• A-DNA was originally identified by X-ray diffraction of DNA fibers at 75% relative humidity.
• Z-DNA has a left-handed double helix structure that winds in a zig-zag pattern.
• C-DNA forms at 66% relative humidity, in the presence of Li+ and Mg2+ ions.
• D-DNA is a rare form with 8 base pairs per helical turn and lacks guanine.
• E-DNA is an extended or eccentric form of DNA.

B-DNA

• James D. Watson and Francis Crick described it.
• Occurs in living organisms under normal conditions.
• Requires low salt concentration and high hydration.
• Two helical polynucleotide chains coil around a common axis.
• Two interchain spacings of grooves are produced by how the helices wind
  • Major groove: 12 Å wide and 8.5 Å deep.
  • Minor groove: 6 Å wide and 7.5 Å deep.
    • Grooves serve as an interactive surface for proteins, chemicals, or drugs binding.
• The molecules wind along two helical paths.
• The chains run in opposite directions and are antiparallel, such that the plane of the bases are perpendicular to helix axis.
• Exhibits right-handed twisting.
• Has a uniform diameter of 20 Å.
• Utilizes complementary base pairing.
• There are 10.4 base pairs per turn.
• The rise per base pair is 3.4 Å.

A-DNA

• One possible double helical structure for DNA along with B-DNA and Z-DNA.
• Features a right-handed double helix.
• Is shorter and thicker than B-DNA.
• It occurs only in dehydrated DNA samples, like those used for crystallographic experiments
• Found using X-ray diffraction analysis of DNA fibers maintained at 75% relative humidity.
• Its grooves are less deep than B-DNA.
• Bases are more tilted (to 20 Å).
• There are 11 base pairs per turn.
• The rise per base pair is 2.3 Å.

Z-DNA

• Discovered in 1984 by Rich, Nordheim, and Wang.
• It is one of the possible DNA double helix structures.
• Features a left-handed double helix where the phosphodiester backbone follows a zig-zag, coining the name Z-DNA.
• Has antiparallel strands like B-DNA.
• It is longer and thinner than B-DNA.
• Adjacent sugars have alternating orientation.
• Contains 12 base pairs per turn, axial rise of 3.8 Å, and a twist angle of 60°.
• Features only one deep helical groove.
• It forms when purines and pyrimidines alternate (GC or AT).
• Dinucleotides, unlike mononucleotides in B-DNA, are its repeating units.

C-DNA

• Forms at 66% humidity, in the presence of Li+ or Mg2+.
• Exhibits right-handed orientation and 3.32 angstroms (Å) of axial rise, per base pair.
• 9.33 base pairs per turn
• 3.32 Å × 9.33 Å = 30.97 Å helical pitch.
• The base pair rotation= to 38.58°.
• Has a 19 Å diameter, less than A- and B-DNA.
• Bases are tilted at 7.8°.

D-DNA

• Extremely rare, with 8 base pairs.
• Found in DNA molecules lacking guanine.
• Axial rise is 3.03 Å per base pair, with a 16.7° tilt from the helical axis.
• Two distinct forms exist: D(A), involved in D-A-B transitions,
• D(B) is associated with D-B confirmation changes.
• 2 DNA structures possess the same helical parameters.

E-DNA

• The presence of cytosine methylation or bromination in the DNA sequence d(GGCGCC)2 induces a unique extended helical conformation called E-DNA.
• Has a long helical axis with the base perpendicular to it.
• Exhibits a deep major groove and a shallow minor groove.
• When allowed to crystallize longer, the methylated form is standard A-DNA.
• E-DNA acts as an intermediate in both the transition to A-DNA and in the crystallographic pathway from B-DNA to A-DNA.