Nucleotides and nucleic acids

1
Nucleotides are the building blocks of nucleic acids
Nucleotides also play other important roles in the cell
Nucleotide
DNA RNA
Roles of nucleotides
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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)
Roles of nucleic acids
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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
Structure of nucleotides
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Fig. 8-1
A phosphate group
Nucleotides have three characteristic components:
A nitrogenous base
(pyrimidines or purine)
A pentose sugar
Structure of nucleosides
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Remove the phosphate group, and you have a nucleoside.
H
ATP is a nucleotide - energy currency
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DG = -50 kJ/mol
triphosphate
Base (adenine)
Ribose sugar
NAD is an important enzyme cofactor
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Fig. 13-15
NADH is a hydride transfer agent,
or a reducing agent.
Derived from Niacin
nicotinamide
Nucleotides play roles in regulation
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Fig. 6-30
Structure of nucleotides
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Below is the general structure of a nucleotide. The
pentose sugar, the base, and the phosphate moieties
all show variations among nucleotides.
Know this!
The ribose sugar
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Ribose
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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
2 3
4
Ribose
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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).

The purine or pyrimidine base
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Pyrimidine and purine
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Fig. 8-1
Know these!
Nucleotide bases in nucleic acids are pyrimidines or purines.
Pyrimidine and purine
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Nucleotide bases in nucleic acids are pyrimidines or purines.
Major bases in nucleic acids
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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
Some minor bases
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Fig. 8-5
5-Methylcytidine occurs in DNA of animals and higher plants
N
6
-methyladenosine occurs in bacterial DNA
Fig. 8-5
The phosphate
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Variation in phosphate group
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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
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Nucleotides in nucleic acids
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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.
Deoxyribonucleotides
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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).
The major deoxyribonucleotides
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Fig. 8-4
Ribonucleotides
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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)
The major ribonucleotides
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Fig. 8-4
Nucleotide nomenclature
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Nucleotide nomenclature
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Fig. 8-39
Nucleic acids
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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.
Sugar-phosphate backbone
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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.
The bases can take syn or anti positions
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Fig. 8-18b
Sugar phosphate backbone conformation
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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.
Compare polynucleotides and polypeptides
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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.
Interstrand H-bonding between DNA bases
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Fig. 8-11
Watson-Crick base pairing
DNA structure determination
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Franklin collected x-ray
diffraction data (early 1950s)
that indicated 2 periodicities
for DNA: 3.4 and 34 .
Watson and Crick proposed a 3-
D model accounting for the data.
DNA structure
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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 , 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.
DNA structure
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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.

Base stacking in DNA
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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.
DNA strands
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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

Nucleic acids
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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
Nucleic acids
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Fig. 8-19
RNA has a rich and varied structure
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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.
RNA displays interesting tertiary structure
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Fig. 8-28 Fig. 8-25
Single-
stranded
RNA
right-
handed
helix
T. thermophila intron,
A ribozyme (RNA enzyme)

(1GRZ)
Hammerhead ribozyme
(1MME)
Yeast tRNA
Phe
(1TRA)
The mother of all biomolecules
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1ffk
Large subunit of the ribosome
(proteins at least)