Core Concepts
In this article, you will learn about the structure and biochemical properties of each DNA tautomer: B-DNA, A-DNA, and Z-DNA.
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What is a Tautomer?
When you think of DNA, a familiar image instantly comes to mind of a twisting ladder-like double helix. However, like many other organic molecules, DNA can take many different forms, called tautomers, given certain environmental conditions. These DNA isomers, known to biochemists as B-DNA, A-DNA, and Z-DNA, have different chemical properties important to biological systems.
Chemists define “tautomerization” as the reaction where two molecule structures spontaneously convert into one another. These two molecules, called tautomers, tend to be constitutional isomers, meaning that they have the same chemical formula but different connectivity between atoms. In fact, many tautomers only differ in the placement of a hydrogen atom. Also, tautomers tend to exist in a state of dynamic equilibrium. This means that the conversion rate of Tautomer A to Tautomer B equals that of B converting to A such that the relative concentrations of A and B remain constant over time.
The keto-enol tautomerism provides the most common example of a tautomer pair in organic and biochemistry.
Unlike other tautomers, B-DNA, A-DNA, and Z-DNA don’t differ in their molecular structure, but rather in the intermolecular interaction between the two helices.
B-DNA Tautomer
For scientists and non-scientists alike, B-DNA serves as the most recognizable form of DNA. Originally imaged by Rosalind Franklin using X-Ray Crystallography, B-DNA served as the basis for the Watson and Crick model of DNA. B-DNA differs from the other tautomers through its handedness, base pair positioning, and sugar pucker.
First, the B-DNA tautomer winds to form a “right-handed” double helix. This means that the strands twist upwards in the counter-clockwise direction, as opposed to “left-handed” double helices which twist upwards clockwise. To remember this distinction, imagine your right hand in front of you. With your thumb pointed upward, curl your fingers into a fist (or a “thumbs-up”). You’ll find your fingers curl counter-clockwise. If you do the same with your left hand, you’ll find your finders curl clockwise when your thumb points upward.
Second, the base pairs of B-DNA form a plane almost perpendicular to that of the helix axis. Put differently, if you orient a double helix of B-DNA vertically, the base pairs form almost perfectly horizontal bridges between the DNA strands.
Third, B-DNA has a sugar pucker conformation called C2’-endo. This refers to the 3D conformation of the DNA’s deoxyribose sugars. Specifically, the C2’-endo pucker indicates that the 2’ carbon of the sugar is oriented the same as the phosphate attached to the 5’ carbon. This orientation then extends the distance between the 5’ and 3’ phosphates compared to the alternate C3’-endo.
A-DNA Tautomer
Despite not having the same fame and recognizability as B-DNA, A-DNA was discovered at the same time through the work of Rosalind Franklin.
Like B-DNA, A-DNA also involves a right-handed helical structure. However, the deoxyribose of A-DNA exhibits a pucker of C3’-endo, which brings the 5’ and 3’ phosphates closer than in B-DNA. This results in A-DNA having a short and squat appearance relative to B-DNA.
Further, A-DNA base pairs exist at an angle 20 degrees from perpendicular to the helical axis. These angled base pairings also connect the strands along the outer surface of the helix, rather than extend across the center as in B-DNA. This results in the double helix becoming “hollow”, with a straw-like hole down the interior of the structure.
Biochemists have found that A-DNA forms under what they call “dehydrating conditions.” This simply means that relatively few water molecules interact with the DNA. The lack of nearby water weakens the “hydrophobic effect,” which is a phenomenon where the polar regions of a biomolecule are drawn to the surface while the non-polar regions are shielded in the interior. In B-DNA, the polar deoxyribose and phosphate backbone interact with water on the outside of the helix. Conversely, the nonpolar regions of the nitrogenous bases form “stacking interactions” crucial to the stability of B-DNA.
Because A-DNA involves base parings along the outside of the helix, only a weakened hydrophobic effect allows A-DNA tautomer formation.
Since its discovery, biochemists have found that bacteria can induce the formation of A-DNA using proteins that strip away solvent. Supposedly, bacteria do this because the A-DNA tautomer better protects genes from conditions of extreme heat or desiccation.
Interestingly, the structure of double stranded RNA resembles that of A-DNA.
Z-DNA Tautomer
Decades after Rosalind Franklin’s discoveries, biochemists Andrew Wang and Alexander Rich found that certain DNA sequences exhibit a third tautomer, termed Z-DNA.
Unlike the other tautomers, Z-DNA has a left-handed helical structure. Relative to A-DNA and B-DNA, Z-DNA has a more elongated and thin helical structure.
Interestingly, Z-DNA has been observed only to form between DNA sequences that alternated purines (adenine and guanine) and pyrimidines (thymine and cytosine). Such sequences could include two strands of alternating guanine and cytosine (poly(GC) – poly(GC)), or one strand of adenine and cytosine paired with another strand of guanine and thymine (poly(AC) – poly(GT)), among a few other sequences.
In Z-DNA, these sequences assume an interesting structure, where purines have a C3’-endo pucker while pyrimidines have a C2’-endo pucker. Additionally, the bonds between the sugars and purine bases rotate to a syn conformation, where the bulk of the base’s ring structures hangs over the deoxyribose. In A-DNA, B-DNA, and Z-DNA pyrimidines, all sugar-to-base bonds have anti confirmations, with the base pointing opposite the sugar.
Like A-DNA, Z-DNA also has an important biological purpose. Specifically, when enzymes open and unwind B-DNA for transcription, Z-DNA forms through “negative-supercoiling” to relieve the stress of unwinding. Indeed, biochemists have identified many different enzymes and binding proteins that specifically interact with Z-DNA, such as the Z-alpha domain.
However, aside from the sequence specifications, Z-DNA has only been observed to form under high salt concentrations. Biochemists believe that the salt ions help stabilize the charged phosphates, which are much closer together in Z-DNA. Without those ions, the structure would lose stability due to the ionic repulsions of the negatively charged phosphates.
DNA Tautomer Summary Table
