DNA

DNA
• Discovered in 1869 by German
doctor Friedrich Miescher, 10-years
after publication of species Darwin’s
Origin of Species & 4-years after
Mendel’s “Experiments in Plant
Hybridization”
•Friedrich Miescher isolated a
substance he called “nuclein” from
large nuclei of white blood cells
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 Source of cells was pus from soiled
surgical bandages

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 DNA

•DNA - a polymer of deoxyribo

nucleotides

•found in chromosomes, mitochondria and

chloroplasts

• carries the genetic information

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Components of a nucleotide

Base

Sugar

Phosphate

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 Base

Phosphate
Sugar
X=H: DNA
X=OH: RNA
Nucleoside
Nucleotide
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 Basic structure of
pyrimidine and purine

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 Purines and Pyrimidines are
nitrogenous bases that make up the two
different kinds of nucleotide bases in
DNA and RNA. The two-carbon nitrogen
ring bases (adenine and guanine)
are purines, while the one-carbon
nitrogen ring bases (thymine and
cytosine) are pyrimidines.

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 Pyrimidines

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 Purines

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 A nucleoside consists of a nitrogenous
base covalently attached to a sugar
(ribose or deoxyribose) but without the
phosphate group. A nucleotide consists
of a nitrogenous base, a sugar (ribose or
deoxyribose) and one to three
phosphate groups.

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Nomenclature of Nucleic Acid Components
Base Nucleoside Nucleotide Nucleic
acid

Purines
Adenine Adenosine Adenylate RNA
Deoxyadenosine Deoxyadenylate DNA
Guanine Guanosine Guanylate RNA
Deoxy guanosine Deoxyguanylate DNA
Pyrimidines
Cytosine Cytidine Cytidylate RNA
Deoxycytidine Deoxycytidylate DNA
Thymine Thymidine Thymidylate DNA
(deoxythymidine) (deoxythymidylate)
Uracil Uridine Biochemistry for Medics
Uridylate RNA 12
 Nucleoside and base analogs can be
used as anti-cancer and anti-virus drugs

Anticancer agents

5-Fluorouracil 6-Mercaptopurine

Antiretroviral agents

Azidothymidine Dideoxyinosine
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DNA structure

 Primary structure

 Secondary structure

 Tertiary structure

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 The primary structure of
DNA is the sequence
5’ end

5’

3’

Phosphodiester
linkage

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3’ end 15
Traditionally, a DNA sequence is
drawn from 5’ to 3’ end.

A shorthand notation for this

sequence is ACGTA
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The secondary structure of
DNA is the double helix

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 The secondary structure of
DNA

Two anti-parallel polynucleotide

chains wound around the same axis.

Sugar-phosphate chains wrap

around the periphery.

Bases (A, T, C and G) occupy the

core, forming complementary A · T
and G · C Watson-Crick base pairs.

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The DNA double helix is held together
mainly by- Hydrogen bonds

 hydrogen bonding;
 base stacking

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 Hydrogen bond

a chemical bond in which a hydrogen atom of

one molecule is attracted to an electronegative
atom, especially a nitrogen, oxygen, or fluorine
atom, usually of another molecule.

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Two hydrogen bonds between A:T pairs
Three hydrogen bonds between C: G paired
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 Base Stacking
The bases in DNA are
planar and have a
tendency to "stack".

Major stacking forces:

hydrophobic interaction
van der Waals forces.

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Biochemistry for Medics 23
Biochemistry for Medics 24
Variations in DNA
• Most of the DNA is in the classic Watson-Crick
model simply called as B-DNA or B-form DNA.
• In certain condition ,different forms of DNAs
are found to be appeared like A-DNA,Z-DNA,C-
DNA,D-DNA,E-DNA.
• This deviation in forms are based on their
structural diversity.
 DNA is generally double stranded, but is single
stranded exceptionally in some Viruses viz.
ȹ- 174 & S-13

 Both strands of DNA are right handed spirals

except Z DNA ( Left handed spiral )

Alternative Forms of DNA

DNA can exist in several conformational isomers
B form is the “normal” conformation
A form is found in high salt conc
Z form Left-handed helix and 12 bp/turn (Z for zigzag)
 DIFFERENT FORMS OF DNA

• X-ray analysis of DNA crystals at atomic resolution have revealed

that DNA exhibits much more structural diversity than formly
envisaged. Such variations are:
 B-DNA: Most common ,originally deduced from X-ray diffraction
of sodium salt of DNA fibres at 92% relative humidity.
 A-DNA: Originally identified by X-ray diffraction of analysis of
DNA fibres at 75% relative humidity .
 Z-DNA: Left handed double helical structure winds to the left in
a zig- zag pattern .
 C-DNA: Formed at 66% relative humidity and in presence of Li+
and Mg2+ ions.
 D-DNA: Rare variant with 8 base pairs per helical
turn ,form in structure devoid of guanine .
 E- DNA: Extended or eccentric DNA.
 A-DNA


 Observed in active site of DNA polymerase

 Gram+ bacteria undergoing sporulation.

 Deep major groove & shallow minor groove.

 Observed under dehydrating conditions.

 B-DNAA-DNA (Reversible).

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A-DNA
• A-DNA is one of the possible double helical
structure which DNA can adopt along with
other two biologically active helix structure(B-
DNA,Z-DNA).
• Right handed double helix .
• Short and fat compared to B-DNA.
• Occur only in dehydrated sample of DNA ,Such
those used in crystallographic experiments.
 B-DNA


 Most common DNA.

 Each base pair has same width.

 Minor groove is narrow & major groove is wide.

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B-DNA
• Described by James D. Watson & Francis crick.
• Commonly found in DNA.
• DNA molecule consists of 2 helical polynucleotide
chains coiled around common axis.
• 2 helices are wound in such a way so as to
produce 2 interchain spacing or groove –
• Major/wide groove(width 12A°,depth 8.5A°)
• Minor /narrow groove(width 6A°,depth 7.5A°)
• These grooves provide surface with which
proteins,chemicals,drugs can interact.
• 2 helical wind along the molecules.
• 2 chains run in opposite direction ,they are
antiparallel ,the plane of bases are perpendicular
to helix axis.
• Right handed twisting .
• Uniform diameter(20A°)
• Complementary base pairing.
• Base pair per turn is 10.4.
• Rise per base pair is 3.4A°.
 Z-DNA


 Seen in conditions of high salt concentration.

 Deep minor groove.

 No discernible major groove.

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Z-DNA
• One of the many possible DNA double helix
structure.
• Left handed double helix structure winds to
left in zig-zag manner.(DNA backbone were in
zig-zag manner)so they are termed as Z-DNA.
• Discovered by Rich, Nordheim &Wang in 1984.
• It has antiparallel strands as B-DNA.
• It is long and thin as compared to B-DNA.
THE ABZs OF DNA

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 TYPES OF DNA
DNAs are of various types A B C D E & Z , of which B
DNA is the most common form . The different types
of DNA differ in number of base pairs per turn, pitch,
angle, diameter of Helix and handed ness etc.

TYPE HANDED BASE PITCH DIAMETE Angle

NESS PAIRS R Between
/TURN 2 bp
A RIGHT 11 28º 23Aº 32.7º

B RIGHT 10 34º 20Aº 36º

Z LEFT 12 69º 18Aº 30º

C RIGHT 9.33 31º 19Aº 38.6º

 DNA CONFIRMATION OF A-,B-&Z-DNA
A B Z
RIGHT HANDED RIGHT HANDED LEFT HANDED
HELIX
WIDEST INTERMEDIATE NARROWEST
WIDTH
PERPENDICULAR TO PERPENDICULAR TO PERPENDICULAR TO
PLANE OF HELIX AXIS HELIX AXIS HELIX AXIS
BASE

6A° HOLES ALONG TINY CENTRAL NO INTERNAL

CENTRAL HELIX AXIS SPACE
AXIS

NARROW & DEEP WIDE &DEEP NO MAJOR GROOVE

MAJOR AXIS
CONFIGURATIONAL DIFFERENCE BETWEEN B-&Z-DNA
B-DNA Z-DNA

COILING RIGHT HANDED LEFT HANDED

NO.OF GROOVE 2 (MAJOR&MINOR) 1(MINOR)

BASE PAIR PER TURN 10.5 12

HELICAL PITCH 34° 44.6°

HELICAL DIAMETER 20° 18°

NUCLEOTIDE ALL ANTI PURINES:SYN

CONFIRMATION CONFIRMATION PYRAMIDINES:ANTI
CHARACTRISTICS A-DNA B-DNA C-DNA Z-DNA

CONDITIONS 75% RELATIVE 92% R.H:;LOW ION 60%R.H;Li/Mg IONS VERY HIGH SALT CONC.
HUMIDITY;NA+,K+,C STRENGTH
s IONS

SHAPE BROADEST INTERMEDIATE NARROW NARROWEST

HELIX SENSE RIGHT RIGHT RIGHT LEFT

HELIX DIAMETER 25.5A° 20.7A° 19.0A° 18.4A°

RISE PER BASE 2.3A° 3.4A° 3.32A° 3.8A°

PAIR(H)

BASE PAIR PER 11 10.4 9.33 12

TURN(N)

HELIX PITCH(H×N) 25.5A° 35.36A° 30.97A° 45.60A°

ROTATION PER BASE +32.72° +34.61° +38.58° -60°

PAIR

BASE PAIR TILT 19° 1° 7.8° 9°

GLYCOSIDIC BOND ANTI ANTI _ ANTI FOR C,T. SYN FOR A,G.

MAJOR GROOVE NARROW &VERY WIDE & QUITE DEEP _ NO

DEEP

MINOR GROOVE VERY BROAD & NARROW & QUITE _ VERY NARROW & DEEP
SHALLOW DEEP
A-DNA

B-DNA

Z-DNA
C-DNA
• C-DNA formed at 66% relative humidity (low)in
presence of Li+ or Mg2+.
• Right handed ,with axial rise of 3.32A° per base
pair .
• 9.33 base pairs per turn.
• Helical pitch 3.32A°×9.33°A=30.97A°.
• Base pair rotation=38.58°.
• Has diameter of19A°,smaller than that of A-&B-
DNA.
• The tilt of base is 7.8°
D-DNA
• Extremely rare variant with only 8base pairs per
helical turn .
• This forms of DNA found in some DNA molecules
devoid of guanine.
• Axial rise of 3.03A°per base pairs .Tilt of 16.7° from axis
of helix.
• Actually 2 different forms of D-DNA
1. D(A):Takes part in D-A-B transition.
2. D(B):Associated with D-B change of confirmation.
• 2 DNA structure have same helical parameters.
E-DNA
• Cytosine methylation of or bromination of DNA
sequence d(GGCGCC)2 is to induce a novel
extended &eccentric double helix, which we call
E-DNA.
• E-DNA has a long helical axis rise and base
perpendicular to the helical axis.
• Deep major groove and shallow minor groove.
• E-DNA allowed to crystallize for a period time
longer, the methylated sequence forms standard
A-DNA.