Nucleic acid

• The term nucleic acid is derived from a Greek word nuclein coined by Friedrich Meisher.
• He isolated pure nucleic acid from DNA protamine complex in salmon sperm nuclei. Later it was
found that nuclein had acid properties and hence alt man in 1899, introduce the term nucleic
acid to replace nuclein.
• They are located in the nuclei of cells certain of them are also present in cytoplasm.
• Nucleic acids are the history determinants of living organisms.
• They are present in most living cells either in the free state or bound to protein as
nucleoproteins.
• They are the bio polymers of high molecular weight with mono nucleotide as the repeating
units.
• Nucleic acid contain carbon hydrogen, oxygen, nitrogen and strangely enough phosphorus.

Structure of nucleic acid

• The two main types of nucleic acid are deoxyribonucleic acid and ribonucleic acid
• DNA is the genetic material found in all organisms ranging from single cell bacteria to
multicellular mammals. It is found in nucleus of eukaryotes and in the organelles ,chloroplast
and mitochondria.
• The other type of nucleic acid, RNA, is mostly involved in protein synthesis.
• The DNA molecules never leave the nucleus but instead use an intermediary to communicate
with the rest of the cell.
• This intermediary is the messenger RNA (mRNA). Other types of RNA—like rRNA, tRNA, and
microRNA—are involved in protein synthesis and its regulation.
• The entire gene content is known as genome.

Phosphoric Acid

The molecular formula of phosphoric acid is H3PO4. It contains 3 monovalent hydroxyl

groups and a divalent oxygen atom, all linked to the pentavalent phosphorus atom.
Pentose Sugar

• The two types of nucleic acids are distinguished primarily on the basis of the 5-carbon keto

sugar or pentose which they possess.

• One possesses D-2-deoxyribose, hence the name deoxyribose nucleic acid or deoxyribonucleic
acid, while the other contains D-ribose, hence the name ribosenucleic acid or ribouncleic acid.
Both these sugars in nucleic acids are present in the furanose form and are of β configuration.
• A perusal of the structure of the two types of sugars reveals that D-ribose is the parent sugar
while D-2-deoxyribose is a derivative in which OH group on C2 has been replaced by an H atom.

Phosphodiester linkage

• An important property of the pentoses is their capacity to form esters with phosphoric acid.
• In this reaction the OH groups of the pentose, especially those at C3 and C5, are involved
forming a 3′, 5′- phosphodiester bond between adjacent pentose
residues.
• This bond, in fact, is an integral part of the structure of nucleic acids.

Nitrogenous Bases

• Two types of nitrogenous bases are found in all nucleic acids. The base is
linked to the sugar moiety by the same carbon (C1) used in sugar-sugar
bonds.
• The nitrogenous bases are derivatives of pyrimidine and purine. Owing to their π electron
clouds, both the pyrimidine and purine bases are planar molecules

PURINES

Adenine
 • Adenine is a two ringed purine derived nucleobase that has an amino group attached to the C6
position. In the nucleotide structure it forms a covalent bond with the ribose/deoxyribose sugar
and hydrogen bond with the adjacent nucleobase, that is either a thymine or uracil.

• Other compounds formed by adenine include vitamin B12, adenosine triphosphate (ATP),
nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD).

Guanine

• Guanine is another two ringed purine derived nucleobase composed of a fused pyrimidine-
imidazole ring system that is conjugated with double bonds. It forms hydrogen bonds with
cytosine in the nucleotide sequence.

• Guanine combines with ribose to form guanosine and with deoxyribose to form deoxyguanosine.

PYRIMIDINES

Thymine

• Thymine is an organic compound that belongs to the pyrimidine family. It forms double
hydrogen bonds with adenine in the DNA helix. It is also known as 5-methyluracil because it is
methylated at the C5 position in the molecule. It is not found in RNA strands.

Cytosine

• Cytosine is a pyrimidine derived nitrogenous base that has an amino group at the C4 position. It
forms triple hydrogen bonds with guanine in the DNA helix.

Uracil

• Uracil is another pyrimidine derived nitrogenous base that is only found in RNA molecules in
place of thymine. It is a demythlated form of thymine that is substituted with oxo groups at C2
and C4.
Modified Nitrogenous Bases
• The above 5 nitrogenous bases were once believed to account for the total base composition

of animal and plant nucleic acids and were hence designated as major nitrogenous bases.

• It is now known that other minor bases called modified nitrogenous bases also occur in
polynucleotide structures.
• Some naturally-occurring forms of modified pyrimidines .
• The 5-methylcytosine (MC) is a common component of plant and animal DNA ; in fact, up to 25%
of the cytosyl residues of plant genome are methylated.
• The DNA of T-even bacteriophages of Escherichia coli has no cytosine but instead has 5-
hydroxylmethylcytosine and its glucoside derivatives.
Nucleosides
• The nucleosides are compounds in which nitrogenous bases (purines and pyrimidines) are
conjugated to the pentose sugars (ribose or deoxyribose) by a β-glycosidic linkage.
• This is, in fact, the configuration in the polymeric nucleic acids.
• The β-glycosidic linkage involves the C-1′ of sugar and the hydrogen atom of N-9 (in the case of

purines) or N-1 (in the case of pyrimidines), thus eliminating a molecule of water.

• Therefore, the purine nucleosides are N-9 glycosides and the pyrimidine nucleosides are N-1
glycosides. Like the O-glycosides, the nucleosides are stable in alkali.
• Purine nucleosides are readily hydrolyzed by acid whereas pyrimidine nucleosides are
hydrolyzed only after prolonged treatment with concentrated acid.
• The nucleosides are generally named for the particular purine or pyrimidine present.
Nucleosides containing ribose are called ribonucleosides, while those possessing deoxyribose
deoxyribonucleosides.

Nucleotide
• Nucleotides are the phosphoric acid esters of nucleosides. These occur either in the free form

or as subunits in nucleic acids. As mentioned earlier, the phosphate is always esterified to the

sugar moiety.

• These are the building blocks of nucleic acids (DNA and RNA).
• They serve as sources of chemical energy (ATP, GTP), participate in cellular signalling (CAMP,
cGMP) and function as important cofactors of enzymatic reactions (CoA, FAD, FMN, NAD*).
• Two main sugars present in furanose form

Structural organisation of DNA(Watson-Crick model)

The salient features of the Watson-Crick model for the commonly-found DNA (known as theB-DNA)
are :

1. DNA molecule consists of two helical polynucleotide chains which are coiled around (or
wrapped about) a common axis in the form of a right handed double helix .
2. The two helices are wound in such a way so as to produce 2 interchain spacing’s or grooves, a
major or wide groove (width 12 Å, depth 8.5 Å) and a minor narrow groove (width 6 Å, depth
narrow groove (width 6 Å, depth7.5 Å).
3. The two grooves arise because the glycosidic bonds of a base pair are not diametrically
opposite each other.
4. The minor groove contains the pyrimidine O-2 and the purine N-3 of the base pair, and the
major groove is on the opposite side of the pair.
5. Each groove is lined by potential hydrogen bond donor and acceptor atoms.
6. It is noteworthy that the major groove displays more distinctive features than does the minor
groove.
7. Also, the larger groove is more accessible to proteins interacting with specific sequences of
DNA.
8. The two helices wind along the molecule parallel to the phosphodiester backbones.
9. These may be visualized as to have formed when two wires are wound about a pencil or a
common axis.
10. The two ribbons represent the phosphate-sugar chains and the horizontal rods represent the
bonding between the pair of bases.
11. Two kinds of grooves, a major and a minor, are evident. The horizontal parallel lines symbolize
hydrogen bonding between complementary bases.
12. The vertical line represents the fibre axis. Note that the structure repeats at
intervals of 34 Å, which corresponds to 10 residues on each chain DNA molecules.

13. Such double helices cannot be pulled apart and can be separated only by an unwinding process.
They are called as plectonemic coils, i.e., coils which are interlocked about the same axis.
14. The two chains run in opposite direction,i.e., they are antiparallel which means that in one
strand, the ring oxygen of sugar moieties face upwards while in the other strand, the ring
oxygen faces downwards. Also they are not identical but, because of base pairing, are
complementary to each other.
15. The phosphate and deoxyribose units are found on the periphery of the helix, whereas the
purine and pyrimidine bases occur in the centre
16. The planes of the bases are perpendicular to the helix axis.
17. The planes of the sugars are almost at right angles to those of the bases.
18. The diameter of the helix is 20 Å. The bases are 3.4 Å apart along the helix axis and are related
by a rotation of 36 degrees.
19. Therefore, the helical structure repeats after 10 residues on each chain, i.e., at intervals of 34 Å.
In other words, each turn of the helix contains 10 nucleotide residues.
20. The two chains are held together by hydrogen bonds between pairs of bases.
21. Adenine always pairs with thymine by 2 hydrogen bonds and guanine with cytosine with 3
hydrogen bonds.
22. This specific positioning of the bases is called base complementarity.
23. The individual hydrogen bonds are weak in nature but, as in the case of proteins, a large
number of them involved in the DNA molecule confer stability to it. It is now thought that the
stability of the DNA molecule is primarily a consequence of van der Waals forces between the
planes of stacked bases.
24. The sequence of bases along a polynucleotide chain is not restricted in any way.
25. The precise sequence of bases carries the genetic information.
26. As a corollary, the entire structure of a DNA molecule resembles a winding staircase, with the
sugar and phosphate molecules of the nucleotides forming the railings and the linked nitrogen
base pairs (A-T and G-C) forming the steps.

Antiparallelity of the polynucleotide chain

• Two complementary chains do not run in the same direction with respect to their

internucleotide linkages, but rather are antiparallel, i.e., one strand runs in the 5′ → 3′ direction

and the other in the 3′ → 5′ direction m.

• Thus, of the two chains, one ascends and the other descends.
• They have reverse polarity, that is to say the sequence of the atoms in the two chains is
opposite to each other.
• This is analogous to 2 parallel streets, each running one way but carrying traffic in opposite
directions.
Characteristic features of A, B, C and Z DNA.
Q)Why do different forms of DNA exist?

Ans) There is simply not enough room for the DNA to be stretched out in a perfect, linear B-DNA
conformation. In nearly all cells, from simple bacteria through complex eukaryotes, the DNA must be
compacted by more than a thousand-fold in order even to fit inside the cell or nucleus.

A-form DNA:

• The right-handed A form is favoured in non aqueous solution

• Most DNA crystallize in this form due to dehydration from crystallization methods.

• The helix is wider than the B form and has 11 base pairs per helical turn (rather than 10.5)

• The plane of the base pairs is tilted about 20° with respect to the helix axis.

• Deeper major groove.

• Shallower minor groove.

• It appears that at least four purines (or pyrimidines) in a row are enough to set up a local A-DNA
helix, although of course certain purine stretches are more likely to form A-DNA than others. (For
example, the sequence AAAA crystallizes as B-DNA, not in the A helix.

• A-DNA helix is less stable than the B-DNA conformation.

• A-DNA is also more rigid than B-DNA, again because the off-centre stacking of the bases makes
them less flexible.
• The base-pair tilt is higher in A-DNA than in B-DN
• The right-handed A-helix is characterized by 11 base pairs per turn (111) symmetry), a rise per
base pair along the helix axis of 2.55 A.

B-form DNA:

• B-DNA is the Watson-Crick form of the double helix that most people are familiar with the right-
sided figure.
• They proposed two strands of DNA each in a right hand helix wound around the same axis. The
two strands are held together by H bonding between the bases (in anti-conformation).
• The two strands of the duplex are antiparallel and plectonemically coiled. The nucleotides
arrayed in a 5' to 3' orientation on one strand align with complementary nucleotides in the 3' to
5' orientation of the opposite strand.
• B-form is the most common form, present in most DNA at neutral pH and physiological salt
concentrations.
• This form is the most stable structure for a random-sequence DNA molecule under physiological
conditions..

• The two helices are wound in such a way so as to produce to interchain spacing or groove.

• Major/wide groove (width 12 A, depth 8.5 A).

• Minor/narrow groove (width 6 A, depth 7.5 A).
• These grooves provide surface with which protein, chemicals, drugs can interact.

Z-form DNA:

• The backbone of the left-handed helix takes on a zigzag appearance and the structure is more
slender and elongated. Z-DNA can form when the DNA is in an alternating purine- pyrimidine
sequence such as GCGCGC, and indeed the G and C nucleotides are in different conformations,
leading to the zig-zag pattern.

• There are 12 base pairs per helical turn.

• Prominent form when pyrimidines alternate with purine, especially alternating C and G. The
purine adopts a syn conformation while the pyrimidine is in the anti conformation.

• The major groove is barely apparent but minor groove is deepen yet narrow.

• It has antiparallel strands as B-DNA.

• It is long and thin compared to B-DNA.

• Does exist lovely though not abundantly.