NUCLEIC ACIDS

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OBJECTIVES

Identify/ recognize nucleic acid  Components in nucleic acid – monosaccharide, nucleobases, phosphoric acid  Differentiate - between 2 types of nucleic acids, DNA and RNA - between nucleotide and nucleoside  Definition – nucleotide, nucleoside, DNA and RNA

Nucleic Acids

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Nucleic acid:

a biopolymer containing three types of monomer units – a nitrogenous base (nucleobases), either purine or pyrimidine – a monosaccharide (aldopentose), either D-ribose or 2 deoxy-D-ribose – phosphoric acid/phospharyl group  Two types - RNA (Ribonucleic Acid) - DNA (Deoxyribonucleic Acid)

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Nucleobases

Nonpolar Heterocylic compounds containing C, H, N, and O Purine and pyrimidine methyl

1 ring structure (C) (T) (U) (G) 2 ring structure (A)

Monosaccharide/sugar

Polar  2 type of aldopentoses found - Ribose (RNA)

Only



anomer present in nucleic acid

- 2-deoxyribose (DNA)  Deoxyribose, derivative of ribose – lacks an oxygen atom at C2

Nucleosides

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Nucleoside:

a compound that consists of D-ribose or 2-deoxy D-ribose (monosaccharide) covalently bonded to a nucleobase by a  N-glycosidic bond  Covalent linkage forms between N9 of purines or N1 pyrimidines to of C1 (anomeric carbon of ribose or 2-deoxyribose) Lack phosphate group Pyrimidine Purine

Nucleotides

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Nucleotide:

a nucleoside in which a molecule of phosphoric acid/phosphoryl group is esterified with an -OH of the monosaccharide, at the 5’-OH  As constituents of cofactors, Coenzyme A (CoA), flavin adenine dinucleotide (FAD) & nicotinamide adenine dinucleotides (NAD) Nucleobase, aldopentose sugar and phosphoryl group Phosphoric acid - polar

5’ = attach to C5 of pentose SUGAR?

NOMENCLATURE of Nucleotide

Based on the nucleoside, plus the phosphate group

Nucleotide Sequence

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Gene: Sequence of nucleotides that encodes a polypeptide, eventually forming a functional protein

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Gene: a discrete unit of hereditary information consisting of a specific nucleotide sequence in DNA (RNA in some viruses)

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The nucleotide sequence is depending on the bases (nucleobases) present

Nucleic Acid:

Biopolymer, nucleotide as monomer DNA RNA Nucleoside 1. Bases = ATGC 2. Aldopentose = Ribose 3. Phosphoryl group 1. Bases = AUGC 2. Aldopentose = Deoxyribose 3. Phosphoryl group Naming of nucleotide: if Base adenine  Deoxyadenosine monophosphate 5’ Naming of nucleotide: if Base adenine  Adenosine 5’monophosphate

Nucleic Acid - DNA and RNA

 DNA stands for deoxyribonucleic acid . It is the genetic code molecule for most organisms.

 RNA stands for ribonucleic acid genetic material.

. RNA molecules are involved in converting the genetic information in DNA into proteins. In retroviruses, RNA is the

NUCLEIC ACIDS ARE POLYMERS OF NUCLEOTIDES

Nucleic Acids

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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 turn is

translated transcribed

into RNA which in into the corresponding protein

DNA

transcription

RNA

translation

protein

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DNA

DNA and RNA are polymers whose monomer units are nucleotides = polynucleotides Polynucleotide = DNA and RNA

Hydrolysis – break bond Condensation – form bond

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Deoxyribonucleic acids,

DNA: a biopolymer that consists of a backbone of alternating units of 2 deoxy-D-ribose and phosphoryl group the 3’-OH of one nucleotide is joined to the 5’ P of the next nucleotide by a phosphodiester bond 3’ 5’ -phosphodiester bond

DNA structure

 Levels of structure – 1° structure : the order of bases on the polynucleotide sequence; the order of bases specifies the genetic code – 2° structure : the three-dimensional conformation of the polynucleotide backbone = double helix structure – 3° structure : supercoiling – 4° structure : interaction between DNA and proteins

DNA - 1 ° Structure

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Primary Structure :

the sequence of bases along the pentose phosphodiester backbone of a DNA molecule – base sequence is read from the 5’ end to the 3’ end – System of notation single letter (A,G,C and T)

Pg 237, Campbell and Farrel. READ!

5’ – G G C A T T G C G C - 3’

On the right 3’ 5’ -phosphodiester bond

Segment of DNA Chain 5’-end

N O C C N H 2 N -2 O 3 PO C CH H H N 2 O C N H H CH N

guanine

O C C CH 3

thymine

CH O P

3’-5’

O O O H O CH 2 O H H C N H H N

cytosine link

O O P

3’-end

O O H O CH 2 O C H H N H H OH H NH 2 C CH CH

• 5’ end – phosphate group is free • 3’end – 3’ OH in deoxyribose is free

DNA - 2 ° Structure

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Secondary structure :

the ordered arrangement of nucleic acid strands 

Double helix:

a type of 2 ° structure of DNA molecules in which two antiparallel polynucleotide strands are coiled in a right-handed manner about the same axis • The chains run antiparallel and are held together by hydrogen bonding between complementary base pairs : A=T, G=C.

DNA double helix

DNA structural elements

 2 right-handed, helical, polynucleotide chains , coiled around a common axis to form a double helix

OH P

 2 characteristic: Major groove and minor groove – binding site for drug or polypeptide  2 strands run in opposite direction (antiparallel) 3’,5’-phosphodiester bridges run in opposite direction  1 base (purine) from single strand link to 1 base (pyrimidine) from other stand (complimentary)  Bases are perpendicular to helix axis  Polarity and non-polarity regions  Aqueous environment – polar, charged, covalent backbone deoxyribose and phosphate groups outside of the helix  Hydrophobic purine and pyrimidine bases avoid water by turning towards the inside of the structure

Groovy DNA

DNA-protein interaction

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T-A Base Pairing

Base pairing is complementary: A=T, G 

C

 A major factor stabilizing the double helix is base pairing by hydrogen bonding between T-A and between C-G  T-A base pair comprised of 2 hydrogen bonds Complementary base pairing

G-C Base Pair

 G-C base pair comprised of 3 hydrogen bonds  G-C base pair comprised of 3 hydrogen bonds

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Forms of DNA

B-DNA

– considered the physiological form – a right-handed helix, inside diameter 11Å – 10 base pairs per turn (34Å) of the helix

A-DNA

– a right-handed helix, but thicker than B-DNA – 11 base pairs per turn of the helix – has not been found in vivo

Z-DNA

• • a left-handed double helix may play a role in gene expression • Z-DNA occurs in nature, usually consists of alternating purine-pyrimidine bases • Methylated cytosine found also in Z-DNA

Structural features of A-, B-, and Z- DNA Type Helical senses Diameter (Å) Base pairs/turn Major groove Minor groove

Pg 294, Concepts in Biochemistry. 3/e 2006 John Wiley & Sons

A-DNA right handed ~26 11 narrow/deep wide/shallow B-DNA right handed ~20 10 wide/deep narrow/deep

20 Å

Z-DNA left handed ~18 12 Flat narrow/deep

DNA - 3 ° Structure

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Tertiary structure:

the three-dimensional arrangement of all atoms of a nucleic acid; commonly referred to as supercoiling 

Supercoiling-

Further coiling and twisting of DNA helix.

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DNA

DNA can forms tertiary structure by twist into complex arrangement – supercoil 

Circular DNA:

a type of double-stranded DNA in which the 5’ and 3’ ends of each strand (2 polynucleotide chains) are joined by phosphodiester bonds  Can be found in microorganisms (bacteriophages, bacteria)  Circular twisted into supercoiled DNA -

3 ° Structure

 Supercoil - results of extra twisting in the linear duplex form

DNA

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Circular DNA:

In microorganisms (bacteriophages, bacteria)  Circular twisted into supercoiled DNA -

3 ° Structure

 In eukaryotes , the 3 ° structure involves histone (protein)-

Chromatin:

DNA molecules wound around particles of histones in a beadlike structure

PROPERTIES OF SUPERCOIL

 Supercoiled is less stable than the relaxed form  Compact hence it more easily stored in the cell  Play a regulatory role in DNA replication

Bacteriophage : DNA – threadlike structure

Super DNA Coiled Topology

  Double helix can be considered to a 2-stranded, right handed coiled rope Can undergo positive/negative supercoiling

Counterclockwise clockwise

DNA - 4 ° Structure

 Four stranded form of DNA (quadruplex DNA)  Role in regulating and stabilizing telomeres and in regulation of gene expression  Small molecules such as porphyrins and anthraquinones present, to stabilize the structure G-quadruplex