2. Nucleotides and nucleic acids
1
Nucleotides are the building blocks of nucleic acids
Nucleotides also play other important roles in the cell
Nucleotide
DNARNA
3. Roles of nucleotides
2
• Building blocks of nucleic acids (RNA, DNA)
•Analogous to amino acid role in proteins
• Energy currency in cellular metabolism (ATP:
adenosine triphosphate)
• Allosteric effectors
• Structural components of many enzyme
cofactors (NAD: nicotinamide adenine
dinucleotide)
4. Roles of nucleic acids
3
• DNA contains genes, the information needed to
synthesize functional proteins and RNAs
• DNA contains segments that play a role in regulation of
gene expression (promoters)
• Ribosomal RNAs (rRNAs) are components of ribosomes,
playing a role in protein synthesis
• Messenger RNAs (mRNAs) carry genetic information
from a gene to the ribosome
• Transfer RNAs (tRNAs) translate information in mRNA
into an amino acid sequence
• RNAs have other functions, and can in some cases
perform catalysis
5. Structure of nucleotides
10/10/05
4 Fig. 8-1
A phosphate group
Nucleotides have three characteristic components:
A nitrogenous base
(pyrimidines or purine)
A pentose sugar
11. Structure of nucleotides
10/10/05
9
Below is the general structure of a nucleotide. The
pentose sugar, the base, and the phosphate moieties
all show variations among nucleotides.
Know this!
13. Ribose
10/10/0511
Fig. 8-3
• Ribose (b-D-furanose) is
a pentose sugar (5-
membered ring).
• Note numbering of the
carbons. In a nucleotide,
"prime" is used (to
differentiate from base
numbering).
5
1
23
4
14. Ribose
10/10/0512
Fig. 8-3
• An important derivative of
ribose is 2'-deoxyribose,
or just deoxyribose, in
which the 2' OH is
replaced with H.
• Deoxyribose is in DNA
(deoxyribonucleic acid)
• Ribose is in RNA
(ribonucleic acid).
• The sugar prefers
different puckers in DNA
(C-2' endo) and RNA C-3'
endo).
18. Major bases in nucleic acids
10/10/05
16 Fig. 8-2
• Among the pyrimidines, C
occurs in both RNA and
DNA, but
• T occurs in DNA, and
• U occurs in RNA
Know these!
• The bases are
abbreviated by their first
letters (A, G, C, T, U).
• The purines (A, G) occur
in both RNA and DNA
19. Some minor bases
10/10/05
17
Fig. 8-5
• 5-Methylcytidine occurs in DNA of animals and higher plants
• N6-methyladenosine occurs in bacterial DNA
Fig. 8-5
21. Variation in phosphate group
10/10/05x
Fig. 8-6, 8-42
• Adenosine 3', 5'-cyclic
monophosphate (cyclic AMP,
or cAMP) is an important
regulatory nucleotide.
• In hydrolysis of RNA by
some enzymes,
ribonucleoside 2',3'-cyclic
monophosphates are isolable
intermediates;
ribonucleoside 3'-
monophosphates are end
products
• Another variation - multiple
phosphates (like ATP).
cAMP
19 10/10/05
22. Nucleotides in nucleic acids
10/10/05
20
• Bases attach to the C-1' of ribose or deoxyribose
• The pyrimidines attach to the pentose via the N-1 position of
the pyrimidine ring
• The purines attach through the N-9 position
• Some minor bases may have different attachments.
23. Deoxyribonucleotides
10/10/0521
Fig. 8-4
2'-deoxyribose sugar
Deoxyribonucleotides are abbreviated (for example) A, or
dA (deoxyA), or dAMP (deoxyadenosine monophosphate)
Phosphorylate the 5' position
and you have a nucleotide(here,
deoxyadenylate or
deoxyguanylate)
with a base (here, a purine,
adenine or guanine)
attached to the C-1'
position is a
deoxyribonucleoside
(here deoxyadenosine and
deoxyguanosine).
25. Ribonucleotides
10/10/05
23 Fig. 8-4
• The ribose sugar with a
base (here, a pyrimidine,
uracil or cytosine) attached
to the ribose C-1' position
is a ribonucleoside (here,
uridine or cytidine).
• Phosphorylate the 5'
position and you have a
ribonucleotide (here,
uridylate or cytidylate)
• Ribonucleotides are abbreviated (for example) U, or UMP
(uridine monophosphate)
29. Nucleic acids
10/10/05
27 Fig. 8-7
Nucleotide monomers
can be linked together via a
phosphodiester linkage
formed between the 3' -OH
of a nucleotide
and the phosphate of the
next nucleotide.
Two ends of the resulting poly-
or oligonucleotide are defined:
The 5' end lacks a nucleotide at
the 5' position,
and the 3' end lacks a nucleotide
at the 3' end position.
30. Sugar-phosphate backbone
10/10/05
28
Berg Fig. 1.1
• The polynucleotide or nucleic acid backbone thus consists of
alternating phosphate and pentose residues.
• The bases are analogous to side chains of amino acids; they vary
without changing the covalent backbone structure.
• Sequence is written from the 5' to 3' end: 5'-ATGCTAGC-3'
• Note that the backbone is polyanionic. Phosphate groups pKa ~ 0.
31. The bases can take syn or anti positions
10/10/05
29 Fig. 8-18b
32. Sugar phosphate backbone conformation
10/10/05
30 Fig. 8-18a
• Polynucleotides have
unrestricted rotation about most
backbone bones (within limits of
sterics)
• with the exception of the sugar
ring bond
• This behavior contrasts with the
peptide backbone.
• Also in contrast with proteins,
specific, predictable interactions
between bases are often formed:
A with T, and G with C.
• These interactions can be
interstrand, or intrastrand.
33. Compare polynucleotides and polypeptides
10/10/05
31
• As in proteins, the sequence of side chains
(bases in nucleic acids) plays an important
role in function.
• Nucleic acid structure depends on the
sequence of bases and on the type of ribose
sugar (ribose, or 2'-deoxyribose).
• Hydrogen bonding interactions are
especially important in nucleic acids.
35. DNA structure determination
10/10/0533
• Franklin collected x-ray
diffraction data (early 1950s)
that indicated 2 periodicities
for DNA: 3.4 Ă… and 34 Ă….
• Watson and Crick proposed a 3-
D model accounting for the data.
36. DNA structure
10/10/05
34
Fig. 8-15
• DNA consists of two helical
chains wound around the
same axis in a right-handed
fashion aligned in an
antiparallel fashion.
• There are 10.5 base pairs, or
36 Ă…, per turn of the helix.
• Alternating deoxyribose and
phosphate groups on the
backbone form the outside
of the helix.
• The planar purine and
pyrimidine bases of both
strands are stacked inside
the helix.
37. DNA structure
10/10/05
35
Fig. 8-15
• The furanose ring usually is
puckered in a C-2' endo
conformation in DNA.
• The offset of the
relationship of the base pairs
to the strands gives a major
and a minor groove.
• In B-form DNA (most
common) the depths of the
major and minor grooves are
similar to each other.
38. Base stacking in DNA
10/10/05
36
Berg Fig. 1.4; 5.13
• C-G (red) and A-T (blue) base
pairs are isosteric (same shape
and size), allowing stacking along
a helical axis for any sequence.
•Base pairs stack
inside the helix.
39. DNA strands
10/10/05
37
Fig. 8-16
• The antiparallel strands of DNA are
not identical, but are complementary.
• This means that they are positioned
to align complementary base pairs: C
with G, and A with T.
• So you can predict the sequence of
one strand given the sequence of its
complement.
• Useful for information storage and
transfer!
• Note sequence conventionally is given
from the 5' to 3' end
40. B,A and Z DNA
10/10/0538
Fig. 8-19
• B form - The most common
conformation for DNA.
• A form - common for RNA
because of different sugar
pucker. Deeper minor groove,
shallow major groove
• A form is favored in conditions
of low water.
• Z form - narrow, deep minor
groove. Major groove hardly
existent. Can form for some
DNA sequences; requires
alternating syn and anti base
configurations.
36 base pairs
Backbone - blue;
Bases- gray
42. RNA has a rich and varied structure
10/10/05
40 Fig. 8-26
Watson-
Crick base pairs
(helical segments;
Usually A-form).
Helix is secondary
structure.
Note A-U pairs in
RNA.
DNA can
form
structures
like this as
well.
