Kusum Yadav

Department of Biochemistry
Email: [email protected] For M. Sc. Biochemistry Sem I

Structure and Properties of Nucleic Acids

Nucleic acids are polymers of nucleotides linked through phosphodiester linkages. Two types of nucleic
acids; Deoxyribonucleic acid (DNA) and Ribonucleic acid (RNA) are present in the cell. Among these
DNA act as a genetic material and inherit the information from one generation to next. RNA comprises
of several types namely messenger RNA (mRNA), ribosomal RNA (rRNA) and transfer RNA (tRNA).
RNA play many other roles like rRNA is component of ribosomes while mRNA contains codons that
are translated into proteins. tRNA transfers corrects amino acid on the growing polypeptide chain by
reading the codons of mRNA.
Nucleotides of DNA and RNA are made up of nitrogenous bases, sugar and phosphate. The sugar that is
present in nucleic acids is pentose sugar which is of two types; one that present in DNA is 2-deoxy-D-
ribose and the other present in RNA is D-ribose. Both the pentoses are present as closed five membered
ring (β-furanose form) (Figure 1).

1
CHO
2
H C OH OH5CH2 O OH5CH2 O
OH OH
3
H C OH 4 1 4 1

4 HO H HO H
H C OH 3 2 3 2
5
CH2OH OH OH OH H
D-Ribose sugar (a pentose) β-D-ribofuranose 2-deoxy-D-ribofuranose
Figure 1: Structure of pentose sugars present in nucleic acids.
Nitrogenous bases are of two types; purines and pyrimidines. The two purine bases of DNA and RNA
are adenine (A) and guanine (G). Among pyrimidines cytosine (C) is present in both DNA and RNA,
thymine (T) is present in DNA only and uracil (U) is present in RNA only. The structure of five major
bases is shown in (Figure 18). The purines and pyrimidens bases contain aromatic ring having
conjugated double bonds structures which absorb light a wavelength near 260nm.

NH2 O

N N N NH

N N N N NH2
Adenine (A) Guanine (G)

NH2 O O

N CH3 NH NH

N O N O N O
H H H
Cytosine (C) Thymine (T) Uracil (U)

Figure 1: Structure of nitrogenous bases present in nucleic acids.

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 Kusum Yadav
Department of Biochemistry
Email: [email protected] For M. Sc. Biochemistry Sem I

The bases, sugar and phosphate linked together to form nucleotide. N-9 (nitrogen 9) of purine bases
form an N-β-glycosyl bond to the C-1 (carbon 1) of the pentoses while N-1 of pyrimidine bases form an
N-β-glycosyl bond to the C-1 of the pentoses. A phosphate molecule is esterified to the 5´ carbon of the
pentose. The nucleotides in DNA are called deoxyribonucleotides or deoxyribonucleosides-5´-
monophosphates form the structural unit of DNA. They are of four types namely; deoxyadenylate
(deoxyadenosine-5´-monophosphate), deoxyguanylate (deoxyguanosine-5´-monophosphate),
deoxycytidylate (deoxycytidine-5´-monophosphate) and deoxythymidylate (deoxythymine-5´-
monophosphate) (Figure 2).

NH2
O
N N N NH
O N N O N N
NH2
-O P O CH2 O -O
P O CH2 O
O
O
OH H
OH H
Deoxyadenylate (deoxyadenosine-5´-monophosphate) Deoxyguanylate (deoxyguanosine-5´-monophosphate)

O
NH2
CH3
NH
N O
O N O
N O -O P O CH2 O
-O P O CH2 O
O
O OH H
OH H
Deoxycytidylate (deoxycytidine-5´-monophosphate) Deoxythymidylate (deoxythymine-5´-monophosphate)
Figure 2: The nucleotides present in DNA.
The nucleotides in RNA are called ribonucleotides or ribonucleotide-5´- monophosphate and are the
structural units of RNA. There are four types of ribonucleotides namely; adenylate (adenosine-5´-
monophosphate), guanylate (guanine-5´-monophosphate), cytidylate (cytidine-5´-monophosphate) and
uridylate (uridine-5´-monophosphate) (Figure 3).
NH2 O

N N N NH
O N O N NH2
N N
-O P O CH2 O -O P O CH2 O
O O
OH OH OH OH

Adenylate (adenosine-5´-monophosphate) Guanylate (guanine-5´-monophosphate)

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Kusum Yadav
Department of Biochemistry
Email: [email protected] For M. Sc. Biochemistry Sem I

NH2 O

N NH
O O
N O N O
-O P O CH2 O -O P O CH2 O

O O
OH OH OH OH
Cytidylate (cytidine-5´-monophosphate) Uridylate (uridine-5´-monophosphate)
Figure 3: The nucleotides present in RNA.

Primary structure of nucleic acids

Nucleotides of both DNA and RNA are covalently linked by phosphate group in which the 5 ′-
phosphate group of one nucleotide unit is attached to the 3 ′ hydroxyl group of the next nucleotide,
forming a phosphodiester linkage. Thus the alternating phosphate and pentose residues form the
covalent backbones and nitrogenous bases form side groups joined to the backbone at regular intervals
(Figure 4). The backbone of both DNA and RNA are hydrophilic as –OH groups of sugar residues form
hydrogen bonds with water. All ends of linear polynucleotide chain has a specific polarity i.e. distinct 5 ′
and 3′ends. The 5′ end has phosphate group at C-5′ of sugar while 3′ end has free -OH group of ribose.
The covalent backbone of RNA is hydrolyzed rapidly in alkaline condition. The 2 ′-OH group acts
nucleophilically on adjacent phosphate group thus hydrolyzing the RNA backbone. Since DNA
backbone lacks 2′-OH, it is stable under similar conditions.

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Kusum Yadav
Department of Biochemistry
Email: [email protected] For M. Sc. Biochemistry Sem I

(A.) Primary structure of DNA (B.) Primary structure of RNA

5’ End 5’ End

O O
-O O- -O O-
P P
O O
Adenine Adenine
CH2 CH2
O O
Phosphodiester
bond
O O OH
-O P -O P
O O

O Cytosine O Cytosine
CH2 O CH2 O

O O OH
-O P O -O P O
O O
O Guanine O Guanine
CH2 O CH2 O

O O OH
-O -O
P O P O
O O
O Thymine O Uracil
CH2 O CH2 O

O O OH
-O P O -O P O
O O
O O

3’ End 3’ End

Figure 4: Primary structure of DNA (A.) and RNA (B.).

The polynucleotide of upto 50 nucleotides is referred as an oligonucleotide. A larger nucleic acid is

called as polynucleotide.
Secondary structure of DNA
James Watson and Francis Crick in 1953 described the three dimensional structure of DNA. It consists
of two polynucleotide chains of DNA wound around the same axis to form right handed double helix

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Kusum Yadav
Department of Biochemistry
Email: [email protected] For M. Sc. Biochemistry Sem I

(Figure 5). The two strands are oriented antiparallel i.e. their 3 ′ and 5′ phosphodiester bonds run in
opposite directions. The sugar and phosphate backbone forms the outer circumference of the double
helix therefore exposed to polar environment having water. The bases of both the strands are stacked
inside the core of the helix makes it hydrophobic. The rings of bases are planer and perpendicular to the
helix axis. The surface of DNA double helix has two grooves, one is called major groove and other is
minor groove. Within the helix each nucleotide base of one strand makes hydrogen bonds in the same
plane with a base of the other strand. A of one strand forms two hydrogen bonds with T of the other
strand and vice versa and G on the one strand forms three hydrogen bonds with Con the other strand
vice versa. So two hydrogen bonds can form between A=T and T=A, and three hydrogen bonds can
form between G≡C and C≡G. Because of these three hydrogen bonds separation of DNA helices needs
more energy when ratio of GC to AT bp is higher.
The two antiparallel polynucleotide chains of DNA helix are not identical but they are complementary
to each other. Whenever A occurs in one strand, T will be present in the other strand and vice versa
similarly whenever G occurs in one chain, C will be present in the other strand and vice versa. The
distance between the stacked bases double helix is 3.4 A °. The distance for making one complete helix
turn is 34 A°. The number of base pairs in each complete turn of double helix is 10.5.The double helix
of DNA is held together by two forces. One is hydrogen bonding between the complementary bases
pairs and second is the base stacking interaction.

5´
3´
Complementary
base pairng
between bases Major
groove

34 Å

Minor
groove

3´
5´

20 Å

Figure 5: Double helical structure of DNA.

The Watson-Crick structure of DNA is also known as B-DNA. There are few deviations from Watson-
Crick DNA double helix structures. The B-DNA is the most stable form of DNA. The two other
structural variations are A-DNA and Z-DNA. A-DNA occurs in solutions that are devoid of water. A-
DNA is right handed double helix. Helix is wider and numbers of base pairs per helix are 11. Z-DNA is
left handed helix and occur when DNA strands contain alternatively G and C repeats. The surface of
helix is zigzag. It is more slender and elongated having 12 base pairs per turn.
mRNA
Whereas DNA contain genetic information, RNA act as an intermediary by using the information coded
in DNA to specify amino acid sequence of a protein. DNA is present in nucleus and protein synthesis
takes place on ribosomes in cytosol. mRNA carries the message from DNA to protein synthesizing
machinery of the ribosome which is present in the cytosol. mRNA is synthesized from DNA through a
process known as transcription. mRNA provides template that specify amino acid sequences in
polypeptide chains.
rRNA

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Kusum Yadav
Department of Biochemistry
Email: [email protected] For M. Sc. Biochemistry Sem I

rRNA are components of ribosomes. The prokaryotic ribosome is made up of two subunits; small
subunit is called 30S subunit and 50S subunit. Small subunit contain 16SrRNA while large subunit
contain 23SrRNA and 5S rRNA. Eukaryotic ribosomes are made up of small (40S) and large (60S)
subunits. Small subunit contain 18S rRNA while large subunit contain 28S rRNA, 5.8S rRNA. RNA
can base pair with complementary regions of either RNA or DNA. G base pairs with C and A base pairs
with U. The paired strands in RNA-RNA or RNA-DNA duplexes are antiparallel. The three
dimensional structures of many RNAs include weak interactions like base-stacking interactions which
stabilize its structure. The RNA double strands are not perfectly complementary. Unlike DNA which
has B-form helix RNA attain A-form of helix. RNA helix contain breaks caused by mismatch or
unmatched bases in one or both the strands which result in bulges or internal loops. Hairpin loops are
also formed between nearby self complementary sequences.

tRNA
tRNA are the small RNA which function as adapter molecules during protein synthesis. Amino acids
are linked covalently at one end while its other end base pair with mRNA. Secondary structure of tRNA
is clover leaf structure made up of four stem loop structure. The aminoacyl stem attaches its cognate
amino acid covalently, the D arm contain the modified base dihydrouridine, the antcodon arm contain
the three anticodons which base pair with the codons on the mRNA, and the TC are which contain
modified base pseudouridine. the three dimensional structure of tRNA is L-shaped structure in which
one leg of the L is formed by acceptor and T stems folded into a continuous A form of double helix. The
other leg is composed of D arm and the anticodon arm. About 25% bases of tRNA are modified or
hypermodified.