Nucleic Acids: Structure and Functionprofkatz.com/courses/.../06/Lecture-19-Nucleic-Acid...Nucleic...
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Nucleic Acids: Structure and Function
Transcript of Nucleic Acids: Structure and Functionprofkatz.com/courses/.../06/Lecture-19-Nucleic-Acid...Nucleic...
Nucleic Acids: Structure and Function
Components of Nucleotides
Hydrolysis of nucleotides gives
phosphoric acid, a pentose sugar, and heterocyclic nitrogenous bases:
HO P
O
OH
OH
-O P
O
O-
O-
H3PO4,Phosphoric Acid PO43-,Phosphate
The building blocks (monomers) of the nucleic acids are called nucleotides.
The pentose sugar found in DNA is 2-deoxy-D-ribose; that found in RNA is D-ribose.
The heterocyclic bases found in DNA are
N
NNH
N
NH2
N
NH
NH2
O
NH
NNH
N
O
NH2
NH
NH
O
O
H3C
adenine cytosine guanine thymine
The heterocyclic bases found in RNA are
N
NNH
N
NH2
N
NH
NH2
O
NH
NNH
N
O
NH2
NH
NH
O
O
adenine cytosine guanine uracil
H
OH
H
CH2
HO H
H HO
HO
H
OH
H
CH2
HO OH
H HO
HO
Structure of a “Nucleoside”
Structure of a “Nucleotide”
Biosynthesis of NucleotidesThe net result of nucleotide biosynthesis can be represented as two dehydration (condensation) reactions:
H
OH
H
CH2
HO H
H HO
HOP
O
OH
OHHO
N
N
NH2
O
H
-2 H2O
Dehydrations
HH
CH2
HO H
H HO
P
O
OH
HO
N
N
NH2
OO
Nucleotide
HH
CH2
HO H
H HO
P
O
OH
HO
N
N
NH2
OO
1’
2’3’
4’
5’ 1
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Note that primed numbers are used for substituents on the sugar ring and unprimed numbers are used for substituents on the heterocyclic ring.
Nucleotide Numbering
Nucleotide NomenclatureNucleotides derived from ribose are called ribonucleotides; those from deoxyribose are called deoxyribonucleotides.
Nucleotide names are usually abbreviated: Deoxy- becomes: d- Heterocyclic base names become: A, C, G, T, U 5’-Monophosphate becomes: MP
dCMP
N
N
NH2
O
HH
CH2
HO H
H HO
P-O
O
O-
AMP
HH
CH2
HO OH
H HO
P-O
O
O-
N
NN
N
NH2
Nucleic Acid Formation from Nucleotides
Nucleic Acid Formation from NucleotidesThe assembly of nucleotides into polynucleotides, or nucleic acids, can be thought of as a dehydration reaction between the 3’-OH of one nucleotide and the phosphate group of a second nucleotide to form a phosphodiester bond.
By convention, nucleotide sequences are named in the 5‘ 3’ direction (a nucleic acid has one 5’-end and one 3’-end).
There may be a phosphate group attached at the 5’-end of the chain or at the 3’-end.
NH
O
ON
O
H
OH
H
HO
HH
CH2OP
HO
O
OH
N
NH2
ON
O
H
OH
H
HO
HH
CH2OP
HO
O
OHDehydration
-H2O
NH
O
ON
O
H
OH
H
O
HH
CH2OP
HO
O
OH
N
NH2
ON
O
H
OH
H
HO
HH
CH2OP
HO
O
NH
O
ONO
HHO
HO
HH
CH2OP
O
O
O
O
HHO
HO
HH
CH2OP
O
O
N
NH2
ONO
HHO
H
O
HH
CH2OP
O
O
O
HHO
HHO
HH
CH2OP
O
O
N
N
N
NH
O
NH2
N
N
N
N
NH2
NH
O
ONO
HH
HO
HH
CH2OP
O
O
O
O
HH
HO
HH
CH2OP
O
O
N
NH2
ONO
HH
H
O
HH
CH2OP
O
O
O
HH
HHO
HH
CH2OP
O
O
N
N
N
NH
O
NH2
N
N
N
N
NH2
H3C
PolynucleotidesDNA Polynucleotide Chain RNA Polynucleotide Chain
T
G
C
A
U
G
C
A
The Three-Dimensional Structure of DNA
The three-dimensional structure of DNA was first deduced by James Watson and Francis Crick in 1953, on the basis of two key pieces of data:
Chargoff rules:
moles of A = moles of T and moles of C = moles of G
for the DNA of any species.
The percentage of A+T or C+G varied from species to species.
DNA x-ray diffraction photographs obtained by Maurice Wilkins and Rosalind Franklin.
The Three-Dimensional Structure of DNA
The three-dimensional structure of DNA is
called the double helix.
In the double helix, two strands of DNA coil about each other, running in opposite directions.
The deoxy-sugars and phosphate groups are located on the outside of the helix and the heterocyclic bases are stacked on
top of each other on the inside of the helix.
Base Pairing
The heterocyclic bases are stacked in pairs, each A across from a T (a), and
each C across from a G (b). The pairs of bases are
held together by hydrogen bonds: two for
an AT base pair, and three for a CG base pair.
SugarPhosphateBackbone
SugarPhosphateBackbone
SugarPhosphateBackbone
SugarPhosphateBackbone
Base Pairing
Illustrating Base Pairing with Electrostatic Diagrams
The Three-Dimensional Structure of DNA
The two deoxynucleotide strands in DNA are complementary to each other: the sequence of bases on the 5‘→3’ strand and the 3‘ →5’ strand are always matched: AT, TA, CG, or GC.
Hydrophobic interactions between the stacked base pairs also contribute significant stability to the double helix.
DNA in the Cell
DNA strands have molecular masses estimated to be from a few billion to 100 billion.
The human genome contains 23 pairs of chromosomes containing 3.2 billion base pairs.
Each DNA molecule is compacted by folding about a structure called a nucleosome core.
Each nucleosome core consists of two pairs each of four different proteins called histones.
DNA in the Cell
Each nucleosome core consists of two pairs each of four different proteins called histones.
Each DNA molecule wraps around the nucleosome cores to form a chain of nucleosomes, each containing 150-200
base pairs.
The chain of nucleosomes is coiled to higher and higher levels to form a compact, highly supercoiled chromatin
fiber.
Structure of RNA
Ribonucleic acids exist as single-stranded molecules. Several types of RNA exist:
Messenger RNA - carries genetic information from DNA to the site of protein synthesis (the ribosome)
Transfer RNA - helps in decoding genetic information by carrying specific amino acids to the ribosome
Ribosomal RNA - forms structural component of the ribosome
Catalytic RNAs - catalyze transformations of other RNAs
Ribonucleic acids exist as single-stranded molecules but have extensive “secondary” and “tertiary” structure. A
good example are the transfer RNA’s.
Artist’s Rendition of Transfer RNA’s
Ribosomal RNA Secondary Structure
Information Flow from DNA to Protein
The Central Dogma of Molecular Biology
Replication is the copying of DNA in the course of cell division.
Transcription is the synthesis of RNA from DNA.
Translation is the synthesis of polypeptides through the combined efforts of rRNA, mRNA, and tRNA.
Approximately 2% of the nucleotides in DNA result in the formation of polypeptides. These regions in the DNA are called coding regions. The remaining
98% of the nucleotides do not appear to have any function and are called junk DNA.
Basic Model of Replication
Semiconservative Replication
