OBJECTIVESOBJECTIVES Identify/ recognize nucleic acidIdentify/ recognize nucleic acid Components in nucleic acid – Components in nucleic acid –
monosaccharide, nucleobases, monosaccharide, nucleobases, phosphoric acidphosphoric acid
Differentiate - between 2 types of Differentiate - between 2 types of nucleic acids, nucleic acids, DNA and RNADNA and RNA
- between nucleotide and - between nucleotide and
nucleosidenucleoside Definition – nucleotide, nucleoside, DNA Definition – nucleotide, nucleoside, DNA
and and RNA RNA
Nucleic AcidsNucleic Acids Nucleic acid:Nucleic acid: a biopolymer containing three types of a biopolymer containing three types of
monomer unitsmonomer units
– a nitrogenous base (nucleobases), either purine or a nitrogenous base (nucleobases), either purine or pyrimidine pyrimidine
– a monosaccharide (aldopentose), either D-ribose or 2-a monosaccharide (aldopentose), either D-ribose or 2-deoxy-D-ribosedeoxy-D-ribose
– phosphoric acid/phospharyl groupphosphoric acid/phospharyl group Two types - RNA (Ribonucleic Acid)Two types - RNA (Ribonucleic Acid)
- DNA (Deoxyribonucleic Acid) - DNA (Deoxyribonucleic Acid)
NucleobasesNucleobases Heterocylic compounds containing Heterocylic compounds containing C, H, N, and OC, H, N, and O Purine and pyrimidinePurine and pyrimidine
1 ring structure
2 ring structure
methyl
Nonpolar
(C) (T) (U)
(A) (G)
2 type of aldopentoses found2 type of aldopentoses found
- Ribose (RNA)- Ribose (RNA)
- 2-deoxyribose (DNA)- 2-deoxyribose (DNA) Deoxyribose, derivative of ribose – lacks an Deoxyribose, derivative of ribose – lacks an
oxygen atom at C2oxygen atom at C2
Monosaccharide/sugarMonosaccharide/sugarPolar
Only anomer present in
nucleic acid
NucleosidesNucleosides
Lack phosphate groupLack phosphate group
Pyrimidine Purine
Nucleoside:Nucleoside: a compound that consists of a compound that consists of D-riboseD-ribose or or 2-deoxy-2-deoxy-D-riboseD-ribose (monosaccharide) covalently bonded to a nucleobase (monosaccharide) covalently bonded to a nucleobase by a by a --N-glycosidic bondN-glycosidic bond
Covalent linkage forms between Covalent linkage forms between N9 of purines or N1N9 of purines or N1 of of pyrimidinespyrimidines to to C1 (anomeric carbon of ribose or 2-deoxyribose)C1 (anomeric carbon of ribose or 2-deoxyribose)
NucleotidesNucleotides Nucleotide:Nucleotide: a a nucleoside nucleoside in in
which a molecule of which a molecule of phosphoric phosphoric acid/phosphoryl group acid/phosphoryl group is is esterified with an -OH of the esterified with an -OH of the monosaccharide, at monosaccharide, at the 5’-OHthe 5’-OH
As constituents of cofactors,As constituents of cofactors,
Coenzyme A (CoA), flavin Coenzyme A (CoA), flavin adenine dinucleotide (FAD) & adenine dinucleotide (FAD) & nicotinamide adenine nicotinamide adenine dinucleotides (NAD) dinucleotides (NAD)
Nucleobase, aldopentose sugar and phosphoryl group
Phosphoric acid - polar
NOMENCLATURE of NOMENCLATURE of NucleotideNucleotide
Based on the nucleoside, plus the phosphate group
Nucleotide SequenceNucleotide Sequence Gene: Sequence of nucleotides that Gene: Sequence of nucleotides that
encodes a polypeptide, eventually encodes a polypeptide, eventually forming a functional proteinforming a functional protein
Gene: a discrete unit of hereditary Gene: a discrete unit of hereditary information consisting of a specific information consisting of a specific nucleotide sequence in DNA (RNA in nucleotide sequence in DNA (RNA in some viruses)some viruses)
The nucleotide sequence is depending on The nucleotide sequence is depending on the bases (nucleobases) present the bases (nucleobases) present
Nucleic Acid:Nucleic Acid:
DNA RNA
1. Bases = ATGC2. Aldopentose =
Ribose3. Phosphoryl group
1. Bases = AUGC2. Aldopentose = Deoxyribose3. Phosphoryl group
Biopolymer, nucleotide as monomer
Naming of nucleotide: if Base adenine Deoxyadenosine 5’ monophosphate
Naming of nucleotide: if Base adenine Adenosine 5’monophosphate
Nucleoside
Nucleic Acid - DNA and RNANucleic Acid - DNA and RNA DNADNA stands for stands for deoxyribonucleic deoxyribonucleic
acidacid. It is the genetic code molecule . It is the genetic code molecule for most organisms.for most organisms.
RNARNA stands for stands for ribonucleic acidribonucleic acid. RNA . RNA molecules are involved in converting molecules are involved in converting the genetic information in DNA into the genetic information in DNA into proteins. In retroviruses, RNA is the proteins. In retroviruses, RNA is the genetic material.genetic material.
NUCLEIC ACIDS ARE POLYMERS OF NUCLEOTIDES
Nucleic Acids DNA or RNA
– consist of a chain of nucleotides joined together by phosphodiester bonds
DNA = material of inheritance, carrier of genetic information
RNA = DNA code is transcribed into RNA which in turn is translated into the corresponding protein
DNAtranscription translation
RNA protein
DNADNA DNADNA and and RNARNA are are polymers polymers
whose monomer unitswhose monomer units are are nucleotides = nucleotides = polynucleotidespolynucleotides
Deoxyribonucleic acids, Deoxyribonucleic acids, DNA:DNA: a biopolymer that a biopolymer that consists of a backbone of consists of a backbone of alternating units of 2-alternating units of 2-deoxy-D-ribose and deoxy-D-ribose and phosphoryl group phosphoryl group
– the 3’-OH of one the 3’-OH of one nucleotide is joined to nucleotide is joined to the 5’ P of the next the 5’ P of the next nucleotide by a nucleotide by a phosphodiester bondphosphodiester bond
Polynucleotide = DNA and RNA
3’ 5’ -phosphodiester bond3’ 5’ -phosphodiester bond
Hydrolysis – break bond
Condensation – form bond
DNA structureDNA structure Levels of structureLevels of structure
– 1° structure1° structure: the order of bases on the : the order of bases on the polynucleotide sequence; the order of polynucleotide sequence; the order of bases specifies the genetic codebases specifies the genetic code
– 2° structure2° structure: the three-dimensional : the three-dimensional conformation of the polynucleotide conformation of the polynucleotide backbone = backbone = double helix structuredouble helix structure
– 3° structure3° structure: supercoiling: supercoiling– 4° structure4° structure: interaction between DNA : interaction between DNA
and proteinsand proteins
DNA - 1° StructureDNA - 1° Structure Primary StructurePrimary Structure:: the the
sequence of bases along sequence of bases along the pentose-the pentose-phosphodiester backbone phosphodiester backbone of a DNA molecule of a DNA molecule – base sequence is read base sequence is read
from the 5’ end to the from the 5’ end to the 3’ end3’ end
– System of notation System of notation single letter (single letter (A,G,C A,G,C and Tand T))
5’ – G G C A T T G C G C - 3’5’ – G G C A T T G C G C - 3’On the right
3’ 5’ -phosphodiester bond3’ 5’ -phosphodiester bond
Pg 237, Campbell and Farrel. READ!
Segment of DNA ChainSegment of DNA Chain
NCCH
C
N
NC
C
N
O
NH2-2
O3POO
CH2
H
O
H
H
HH
NC CH
N
O
CC
O
CH3
O P
O
OO
CH2
H
O
H
H
HH
NC CH
N
O
CHC
NH2
O P
O
OO
CH2
H
OH
H
H
HH
5’-end
3’-end
guanine
thymine
cytosine3’-5’link
• 5’ end – phosphate group is free
• 3’end – 3’ OH in deoxyribose is free
DNA - 2° StructureDNA - 2° Structure Secondary structureSecondary structure:: the ordered the ordered
arrangement of nucleic acid arrangement of nucleic acid strandsstrands
Double helix:Double helix: a type of 2° a type of 2° structure of DNA molecules in structure of DNA molecules in which which two antiparallel two antiparallel polynucleotide strandspolynucleotide strands are coiledare coiled in a right-handed manner about in a right-handed manner about the same axis the same axis
• The chains run The chains run antiparallelantiparallel and are and are held together by hydrogen held together by hydrogen bondingbonding between between complementary complementary base pairsbase pairs: A=T, G=C.: A=T, G=C.
DNA double helix
DNA structural elementsDNA structural elementsOH P
2 right-handed, helical, polynucleotide chains2 right-handed, helical, polynucleotide chains, , coiled around a common axis to form a double helixcoiled around a common axis to form a double helix
2 characteristic: 2 characteristic: Major groove and minor groove Major groove and minor groove – – binding site for drug or polypeptidebinding site for drug or polypeptide
2 strands run in opposite direction 2 strands run in opposite direction
(antiparallel)(antiparallel)-3’,5’-phosphodiester bridges run in -3’,5’-phosphodiester bridges run in opposite directionopposite direction
1 base (purine) 1 base (purine) from single strand link tofrom single strand link to
1 base (pyrimidine) 1 base (pyrimidine) from other stand from other stand (complimentary) (complimentary)
BasesBases are are perpendicularperpendicular to helix to helix axisaxis Polarity and non-polarity regions Polarity and non-polarity regions Aqueous environment – polar, charged, covalent Aqueous environment – polar, charged, covalent
backbone deoxyribose and phosphate groups backbone deoxyribose and phosphate groups outside of the helixoutside of the helix
Hydrophobic purine and pyrimidine bases avoid Hydrophobic purine and pyrimidine bases avoid water by turning towards the inside of the structurewater by turning towards the inside of the structure
T-A Base PairingT-A Base Pairing Base pairing is complementary: Base pairing is complementary: A=T, GA=T, GCC
A major factor stabilizing the double helix is base A major factor stabilizing the double helix is base pairing by hydrogen bonding between T-A and pairing by hydrogen bonding between T-A and between C-Gbetween C-G
T-A base pairT-A base pair comprised of comprised of 22 hydrogen bondshydrogen bonds
Complementary base pairing
G-C Base PairG-C Base Pair
G-C base pair comprised of 3 hydrogen bondsG-C base pair comprised of 3 hydrogen bonds
G-C base pairG-C base pair comprised of 3 comprised of 3 hydrogen bondshydrogen bonds
Forms of DNAForms of DNA B-DNA B-DNA
– considered the considered the physiological formphysiological form– a right-handed helix, inside diameter 11Åa right-handed helix, inside diameter 11Å– 10 base pairs per turn (34Å) of the helix10 base pairs per turn (34Å) of the helix
A-DNAA-DNA– a right-handed helix, but thicker than B-DNAa right-handed helix, but thicker than B-DNA– 11 base pairs per turn of the helix11 base pairs per turn of the helix– has not been found has not been found in vivoin vivo
Z-DNAZ-DNA• a left-handed double helixa left-handed double helix• may play a role in gene expressionmay play a role in gene expression
• Z-DNA occurs in nature, usually consists of Z-DNA occurs in nature, usually consists of alternating purine-pyrimidine basesalternating purine-pyrimidine bases
• Methylated cytosine found also in Z-DNAMethylated cytosine found also in Z-DNA
Structural features of A-, B-, and Z- DNA
Type A-DNA B-DNA Z-DNAHelical senses right handed right handed left handedDiameter (Å) ~26 ~20 ~18Base pairs/turn 11 10 12Major groove narrow/deep wide/deep FlatMinor groove wide/shallow narrow/deep narrow/deep
Pg 294, Concepts in Biochemistry. 3/e 2006 John Wiley & Sons
20 Å
DNA - 3° StructureDNA - 3° Structure Tertiary structure:Tertiary structure: the the
three-dimensional three-dimensional arrangement of all atoms arrangement of all atoms of a nucleic acid; of a nucleic acid; commonly referred to as commonly referred to as supercoilingsupercoiling
Supercoiling-Supercoiling- Further Further coiling and twisting of coiling and twisting of DNA helix.DNA helix.
DNADNA DNA can forms tertiary structure by twist DNA can forms tertiary structure by twist
into complex arrangement – supercoilinto complex arrangement – supercoil Circular DNA:Circular DNA: a type of double-stranded a type of double-stranded
DNA in which the 5’ and 3’ ends of each DNA in which the 5’ and 3’ ends of each strand (2 polynucleotide chains) are strand (2 polynucleotide chains) are joined by phosphodiester bondsjoined by phosphodiester bonds
Can be found in Can be found in microorganisms microorganisms (bacteriophages, bacteria)(bacteriophages, bacteria)
Circular twisted into supercoiled Circular twisted into supercoiled
DNA - DNA - 3° Structure3° Structure Supercoil - results of extra Supercoil - results of extra
twisting in the linear duplex form twisting in the linear duplex form
DNA DNA Circular DNA:Circular DNA: In microorganisms In microorganisms
(bacteriophages, bacteria)(bacteriophages, bacteria)
Circular twisted into supercoiled Circular twisted into supercoiled DNA - DNA - 3° Structure3° Structure
In In eukaryoteseukaryotes, the 3° structure , the 3° structure involves histone (protein)- involves histone (protein)- Chromatin:Chromatin: DNA molecules DNA molecules wound around particles of wound around particles of histones in a beadlike structure histones in a beadlike structure
PROPERTIES OF PROPERTIES OF SUPERCOILSUPERCOIL
Supercoiled is less stable than the relaxed Supercoiled is less stable than the relaxed formform
Compact hence it more easily stored in the Compact hence it more easily stored in the cellcell
Play a regulatory role in DNA replicationPlay a regulatory role in DNA replication
Super DNA Coiled TopologySuper DNA Coiled Topology Double helix can be considered to a 2-stranded, Double helix can be considered to a 2-stranded,
right handed coiled roperight handed coiled rope Can undergo positive/negative supercoilingCan undergo positive/negative supercoiling
clockwise
Counterclockwise
DNA - 4° StructureDNA - 4° Structure Four stranded form of DNA (quadruplex DNA)Four stranded form of DNA (quadruplex DNA) Role in regulating and stabilizing telomeres and in Role in regulating and stabilizing telomeres and in
regulation of gene expressionregulation of gene expression Small molecules such as porphyrins and Small molecules such as porphyrins and
anthraquinones present, to stabilize the structureanthraquinones present, to stabilize the structure
G-quadruplex