Nucleic Acids

NUCLEOTIDES

Nucleotides and deoxynucleotides are the building blocks that comprise the DNA and RNA polymers. Nucleotides are made up of ribose or deoxyribose sugars, a nitrogenous base, and one or more phosphate groups. If there are no phosphates, the molecule is called a nucleoside. As an example, examine guanosine triphosphate (GTP).

With a spacefill model, we can examine a more literal atomic structure of the base.

This view could have been displayed using the Jmol menu (Render -> Scheme -> CPK spacefill). For a more familiar view, try changing the view of the base into ball & stick (Render -> Ball and Stick).

Purines and pyrimidines

Nucleotides and deoxynucleotides can be divided into two classes: those with a double ring base known as the purines, and those with a single ring base known as the pyrimidines. There are five nitrogenous bases used in DNA and RNA: adenine and guanine are the purines, and cytosine, thymine, and uracil are the pyrimidines. RNA is built from the nucleotides ATP,GTP, CTP and UTP. DNA is built from the deoxy-nucleotides dATP, dGTP, dCTP, and dTTP.

NUCLEIC ACIDS AS POLYMERS

In cells nucleic acids DNA and RNA are formed from the condensation of nucleotides. This process is catalyzed by enzymes called polymerases. PPi is lost during polymerization, so each residue in the polymer retains just a single phosphate group. DNA is composed of deoxynucleotides connected by phosphodiester bonds.

Asymmetry

This phosphodiester linkage provides directionality to the resulting polymer. One end of a DNA or RNA chain is known as the 5’ end, and has a phosphate group attached to the 5’ carbon of the ribose sugar. The other end of the chain is called the 3’ end and has a free hydroxyl on the 3’ carbon of the ribose group.

Watch as this single strand of DNA is built–one nucleotide at a time.

Polymerization

The polymerases that copy our genetic material do not polymerize nucleotides as we have just shown, for genetic information requires that nucleic acids are copied. Instead, polymerases copy a template strand by creating a new complementary strand, adding one base-pairing nucleotide monomer at a time to the 3' end of the growing nucleic acid chain.

DNA Structure

Double stranded in the cell

Inside a cell DNA is structured as two chains bound snugly next to each other head to tail rather than as a single chain. The chains, sometimes referred to as strands, are oriented in opposing directions. Specifically, the 5’ end of one chain is lined up next to the 3’ end of the opposite strand.

DNA secondary structure: helix

The DNA helix is right-handed helix. If you were to ascend the DNA helix like a spiral staircase, you would hold the DNA sugar-phosphate backbone in your right hand.

Rotate the molecule 180 degrees and examine the helix. Is it still right-handed?

Stacking interactions

The DNA molecule's stability and rigidity is due to stacking interactions between thousands or millions of adjacent bases. These stacking interactions are a form of van der Waals interaction. The stacking interaction between neighboring G:C base pairs is stronger than between A:T base pairs. For this reason, a double-stranded DNA molecule rich in GC will “melt,” or denature, into its composite single strands at a higher temperature than an AT-rich molecule.

Base pairing

DNA chains are complementary to each other because every purine on one chain has a corresponding pyrimidine on the opposite strand. More specifically, every A on one chain "base-pairs" to a corresponding T on the opposite strand, likewise C is matched with G:

Thus, a cellular DNA chain will have a matching complement strand. Adherance to these rules of base pairing is what makes nucleic acids especially suited for storage and transmission of genetic information.

Examine this DNA helix and see if you can notice the similar backbone-to-backbone sizes and geometry of the A:T and G:C base pairs. Why do you think this is? Do the base pair rules make sense in this regard?

What type of interaction is responsible for complementary base pairing? Why do adenosine bases have an affinity for thymine bases on the opposing DNA strand? While the stacking forces make the structure very stable, they are non-specific interactions directed along the axis of the DNA molecule–not between chains. The answer is that the bases are held together across the chains by hydrogen bonding. There are two hydrogen bonds between thymine and adenine and three between guanine and cytosine.

Note that the hydrogen bonds are shown as thin, broken lines, not as the larger solid lines used for covalent bonds.

Major and minor groove

The major and minor grooves of the DNA helix are exposed on the outside of the helix, while the base-pairing between strands is protected within the interior. Note that the bases of the nucleotides are found in the interior of the molecule isolated from the aqueous environment.

The true topology of DNA's major and minor grooves is more clearly seen when the atoms are rendered in spacefill, using their van der Waals radii.

Note the dramatic difference in width between the two grooves of DNA.

Other double stranded DNA structures

The DNA double helix shown in the preceding examples is known as B-DNA and is characterized by a specific size and incline. DNA is believed to have other possible, yet less common, conformations–one of which is called A-DNA. Examine this new structure of A-DNA.

RNA STRUCTURE

RNA is also a polymer of nucleotides. Typical mRNA molecules are a few thousand nucleotides in length. The RNA molecule, unlike DNA, is generally single-stranded. Press the Display button to view an RNA segment known as a pseudoknot.

RNA secondary structure: knotted

RNA is less rigid than the double-stranded DNA helix, and its bases are free to pair with other bases in the molecule. Because of these intramolecular base pairings, the molecule is often elaborately convoluted. Unlike DNA, some RNA bases are exposed to the aqueous environment. Press the Display button to view a transfer RNA (tRNA), a nucleic acid involved in protein sythesis.

Examine the wireframe and note the compact "L" shape of the tRNA. All tRNA molecules have a well defined shape that is stabilized by intramolecular base-pairing and stacking interactions.