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DNA
Double helix
Stores genetic code as a linear
sequence of bases
20 in diameter
Human genome 3.3 x 109 bp
25,000 genes
Richard Lavery
Institut de Biologie Physico-Chimique, Paris
Chemical bond
(10-10 m)
Amino acid
10
(10-9 m)
Globular protein
100
(10-8 m)
Virus
1000 (10-7 m)
Cell nucleus
1 m
(10-6 m)
Bacterial cell
5 m
(10-5 m)
Chromosome DNA
10 cm
(10-1 m)
DNA BASES
OH ribose
H deoxyribose
Nucleoside
Nucleotide
Richard Lavery
Institut de Biologie Physico-Chimique, Paris
Richard Lavery
Institut de Biologie Physico-Chimique, Paris
N7
C5
C4
C6
C8
N1
N9
C4
C2
C5
C6
N3
C2
N1
N3
Purine (Pur / R)
Pyrimidine (Pyr / Y)
Base families
Richard Lavery
Institut de Biologie Physico-Chimique, Paris
NH2
7
N
9N
NH
8
H
Purine
N
H
N
H
Adenine (A)
Guanine (G)
NH2
4
5
NH2
H3C
NH
NH
2
N1
H
Pyrimidine
Natalia Tretyakova
College of Pharmacy, U. of Minnesota
N
H
Cytosine (C)
N
H
N
H
Thymine (T)
Uracil (U)
(DNA only)
(RNA only)
Purine Bases
The 9 atoms that make up the fused rings (5 carbon, 4 nitrogen) are numbered 1-9.
All ring atoms lie in the same plane.
Richard B. Hallick
Introductory Course in Biology or Biochemistry
Purine Nucleotides
Natalia Tretyakova
College of Pharmacy, U. of Minnesota
Pyrimidine Bases
All pyrimidine ring atoms lie in the same plane.
Richard B. Hallick
Introductory Course in Biology or Biochemistry
Pyrimidine Nucleotides
Natalia Tretyakova
College of Pharmacy, U. of Minnesota
Nomenclature of nucleobases, nucleosides,
and mononucleotides
nucleobase
(Deoxy)
nucleoside
Adenine (A)
2-Deoxyadenosine
(dA)
2- Deoxyguanosine
(dG)
2- Deoxythymidine
(dT)
2- Deoxycytidine
(dC)
Uridine (U)
Guanine (G)
Thymine (T)
Cytosine (C)
Uracil (U)
Natalia Tretyakova
College of Pharmacy, U. of Minnesota
5-mononucleotide
Deoxyadenosine 5-monophosphate
(5-dAMP)
Deoxyguanosine 5-monophosphate
(5-dGMP)
Deoxythymidine 5-monophosphate
(5-dTMP)
Deoxycytidine 5-monophosphate
(5-dCMP)
Uridine 5-monophosphate (5-UMP)
RNA
O
O
H3C
NH
NH
N
O
H
Uracil (U)
N
O
H
Thymine (T)
HO
CH2
Base
CH2
2'-deoxyribose
Natalia Tretyakova
College of Pharmacy, U. of Minnesota
HO
Base
OH
ribose
Deoxyribose Sugar
The hydroxyl groups on the 5'- and 3'carbons link to the phosphate groups
to form the DNA backbone.
Richard B. Hallick
Introductory Course in Biology or Biochemistry
Nucleosides
A nucleotide is a nucleoside with one
or more phosphate groups covalently
attached to the 3'- and/or 5'-hydroxyl
group(s).
Richard B. Hallick
Introductory Course in Biology or Biochemistry
NH2
N
N
HO
N
O
HO
OH
OH
Syn conformation
Anti conformation
Sugar puckers:
5.9 A
HO
2'
5'
7.0 A
O
3'
BASE
1'
H (OH)
HO
Natalia Tretyakova
College of Pharmacy, U. of Minnesota
HO HO
5'
3'
BASE
1'
H (OH)
3' endo (RNA)
HO
O
P O
HO
HO
O
Base
Kinase
ATP
OH
Base
OH
Mo no ph osphate
ATP
O
O
O
HO P O P O P O
HO
OH OH
O
OH
Triphosp ha te
Natalia Tretyakova
College of Pharmacy, U. of Minnesota
Base
Kinase
ATP
O
O
HO P O P O
HO
OH
Kinase
O
OH
Di phosphat e
Base
Thymine -Adenine
Cytosine -Guanine
Richard B. Hallick
Introductory Course in Biology or Biochemistry
To
y
ox
e
d
os
b
ri
To
Minor groove
Natalia Tretyakova
College of Pharmacy, U. of Minnesota
de
ox
y
r ib
ose
Backbone structure:
Richard B. Hallick
Introductory Course in Biology or Biochemistry
B-DNA STRUCTURE
B-DNA Structure
20
GC
AT
CG
CGCGTTGACAACTGCAGAATC
34
TA
TA
GC
AT
Major
Groove
TA
3.4
Strands are
antiparallel
Richard Lavery
Institut de Biologie Physico-Chimique, Paris
Minor
Groove
CG
CG
GC
AT
GC
R.H. helix
Natalia Tretyakova
College of Pharmacy, U. of Minnesota
Natalia Tretyakova
College of Pharmacy, U. of Minnesota
B-DNA
right handed helix
helical axis passes through
base pairs
23.7 A
7.0 A
BASE
1'
H (OH)
HO
2'
5'
HO
OH
Helical pitch = 34 A
DNA grooves
Richard Lavery
Institut de Biologie Physico-Chimique, Paris
To deoxyribose-C1
Base
C1 -To deoxyribose
Base
Major groove
Major groove
H2N
NH
N
N
y
ox
e
od
o
rib
C-1
e
s
Natalia Tretyakova
College of Pharmacy, U. of Minnesota
N
N
C-1
N
NH2
Minor groove
NH2
C-1
To
d
O
HN
O
eox
yr i
bo
se
Minor groove
N
C-1
H2
N
NH
N
N
To
de
os
ib
r
y
ox
NH2
e C-1
C-1T
NH2
N
N
C-1
O
HN
O
Natalia Tretyakova
College of Pharmacy, U. of Minnesota
eox
Minor groove
od
N
C-1
yr i
bo
se
CH2
Base
OH
ribose
steric clash
Natalia Tretyakova
College of Pharmacy, U. of Minnesota
A-DNA STRUCTURE
De-hydration
Hydration
5
3
3
5
Antiparallel
strands
R.H. helix
25.5 A
Top View
Natalia Tretyakova
College of Pharmacy, U. of Minnesota
O
2'
5'
7.0 A
O
3'
BASE
1'
H (OH)
O
2' endo (3' exo) B-DNA
Natalia Tretyakova
College of Pharmacy, U. of Minnesota
O
5'
3'
BASE
1'
O
2'
H (OH)
3' endo (A-DNA)
Major groove
O H2N
To
se N
o
ib
yr
x
o
de
NH
N
NH2
Minor groove
Major groove
N To d
eo
xy
rib
os
e
Helix axis
To
B-DNA
Natalia Tretyakova
College of Pharmacy, U. of Minnesota
O H2N
e
os
ir b
y
ox
e
d
NH
N
NH2
Minor groove
A-DNA
N To d
eo
xy
rib
os
e
Z-DNA STRUCTURE
L.H. helix
Natalia Tretyakova
College of Pharmacy, U. of Minnesota
N
HO
2'
5'
O
3'
HO
C
Natalia Tretyakova
College of Pharmacy, U. of Minnesota
N
1'
HN
O
H2N
HO HO
5'
N
3'
1'
Natalia Tretyakova
College of Pharmacy, U. of Minnesota
NH2
H3C
N
N
H
5-methylcytosine (5-Me-C)
Natalia Tretyakova
College of Pharmacy, U. of Minnesota
Backbone Dihedrals
Backbone dihedrals - I
Richard Lavery
Institut de Biologie Physico-Chimique, Paris
+10
+60
Staggered
Eclipsed
gauche +
gauche -
trans
Favoured conformations
Richard Lavery
Institut de Biologie Physico-Chimique, Paris
O3 P O5 C5
g-
P O5 C5 C4
O5 C5 C4 C3
g+
C5 C4 C3 O3
g+
C4 C3 O3 P
C3 O3 P O5
g-
(Y) :
O4 C1 N1 C2
(R) :
O4 C1 N9 C4
Backbone dihedrals - II
Richard Lavery
Institut de Biologie Physico-Chimique, Paris
g-
C5
Base
ENDO
EXO
Sugar pucker
described as
pseudorotation
North : C3-endo
East : O4-endo
South : C3-endo
"2 B or not 2 B ...."
W. Shakespeare 1601
tan P = (4 - 1) - (3 - 0)
22 (Sin 36 + Sin72)
1
Amp = 2 / Cos P
Pseudorotation Equations
Altona et al. J. Am. Chem. Soc. 94, 1972, 8205
Base
Reversed Watson-Crick
Watson-Crick
Hoogsteen
Reversed Hoogsteen
Richard Lavery
Institut de Biologie Physico-Chimique, Paris
Richard Lavery
Institut de Biologie Physico-Chimique, Paris
Quadruplex DNA
Richard Lavery
Institut de Biologie Physico-Chimique, Paris
Richard Lavery
Institut de Biologie Physico-Chimique, Paris
Holliday junction
DNA cruciform
Richard Lavery
Institut de Biologie Physico-Chimique, Paris
Richard Lavery
Institut de Biologie Physico-Chimique, Paris
Richard Lavery
Institut de Biologie Physico-Chimique, Paris
Richard Lavery
Institut de Biologie Physico-Chimique, Paris
Parallel-stranded DNA
Single strands
TM
duplex
70
80
90
100
T, C
Duplex stability is affected by DNA length, % GC base pairs, ionic strength, the
presence of organic solvents, pH
Natalia Tretyakova
College of Pharmacy, U. of Minnesota
Books on DNA
Richard Lavery
Institut de Biologie Physico-Chimique, Paris
HISTORY of DNA
1865
1869
1892
1920
1938
Gregor Mendel publishes his work on plant breeding with the notion
of "genes" carrying transmissible characteristics
"Nuclein" is isolated by Johann Friedrich Miescher Tbingen
in the laboratory of Hoppe-Seyler
Meischer writes to his uncle "large biological molecules composed
of small repeated chemical pieces could express a rich language in
the same way as the letters of our alphabet"
Recognition of the chemical difference between DNA and RNA
Phoebus Levene proposes the "tetranucleotide hypothesis"
William Astbury obtains the first diffraction patters of DNA fibres
History of DNA
Richard Lavery
Institut de Biologie Physico-Chimique, Paris
1944
History of DNA
Richard Lavery
Institut de Biologie Physico-Chimique, Paris
1950
History of DNA
Richard Lavery
Institut de Biologie Physico-Chimique, Paris
1953
Watson and Crick propose the double helix as the structure of DNA
based on the work of Erwin Chargaff, Jerry Donohue, Rosy Franklin
and John Kendrew
History of DNA
Richard Lavery
Institut de Biologie Physico-Chimique, Paris
Rosalind Franklin
Natalia Tretyakova
College of Pharmacy, U. of Minnesota
Francis Crick
Jim Watson
Double helix ?
Richard Lavery
Institut de Biologie Physico-Chimique, Paris
Nucleic Acids
DNA
RNA
(ribonucleic acids)
(deoxyribonucleic acids)
replication
DNA
RNA
Proteins
transcription translation
DNA
Natalia Tretyakova
College of Pharmacy, U. of Minnesota
Cellular Action