Chapter 19 (part 1)

Nucleic Acids

• Information encoded in a DNA molecule is transcribed via synthesis of an RNA molecule

• The sequence of the RNA molecule is "read" and is translated into the sequence of amino acids in a protein.

Nucleic Acids Are Essential For Information Transfer in Cells

Central Dogma of Biology

Nucleic Acids

• First discovered in 1869 by Miescher.

• Found as a precipitate that formed when extracts from nuclei were treated with acid.

• Compound contained C, N, O, and high amount of P.

• Was an acid compound found in nuclei therefore named nucleic acid

Nucleic Acids

• 1944 Oswald, Avery, MacLeod and McCarty demonstrated that DNA is the molecule that carrier genetic information.

• 1953 Watson and Crick proposed the double helix model for the structure of DNA

Nucleic Acids• Nucleic acids are long polymers of

nucleotides.• Nucleotides contain a 5 carbon

sugar, a weakly basic nitrogenous compound (base), one or more phosphate groups.

• Nucleosides are similar to nucleotides but have no phosphate groups.

Pentoses of Nucleotides

• D-ribose (in RNA) • 2-deoxy-D-ribose (in

DNA) • The difference - 2'-

OH vs 2'-H • This difference

affects secondary structure and stability

Nitrogenous Bases

Bases are attached by -N-glycosidic linkages to 1 carbon of pentose sugar – (Nucleoside)

Nucleosides• Base is linked via a -N-

glycosidic bond • The carbon of the

glycosidic bond is anomeric

• Named by adding -idine to the root name of a pyrimidine or -osine to the root name of a purine

• Conformation can be syn or anti

• Sugars make nucleosides more water-soluble than free bases

Anti- conformation predominates in nucleic acid polymers

Nucleotides• Phosphate ester of nucleosides

The plane of the base is oriented perpendicular to the plane of the pentose group

Other Functions of Nucleotides

• Nucleoside 5'-triphosphates are carriers of energy

• Bases serve as recognition units • Cyclic nucleotides are signal

molecules and regulators of cellular metabolism and reproduction

• ATP is central to energy metabolism

• GTP drives protein synthesis • CTP drives lipid synthesis • UTP drives carbohydrate

metabolism

• Nucleotide monomers are joined by 3’-5’ phosphodiester linkages to form nucleic acid (polynucleotide) polymers

• Nucleic acid backbone takes on extended conformation.

• Nucleotide residues are all oriented in the same direction (5’ to 3’) giving the polymer directionality.

• The sequence of DNA molecules is always read in the 5’ to 3’ direction

Nucleic Acids

Bases from two adjacent DNA strands can hydrogen bond

•Guanine pairs with cytosine

•Adenine pairs with thymine

Base pairing evident in DNA compositions

H-bonding of adjacent antiparallel DNA strands form double helix structure

Properties of DNA Double Helix

• Distance between the 2 sugar-phosphate backbones is always the same, give DNA molecule a regular shape.

• Plane of bases are oriented perpendicular to backbone

• Hydrophillic sugar phosphate backbone winds around outside of helix

• Noncovalent interactions between upper and lower surfaces of base-pairs (stacking) forms a closely packed hydrophobic interior.

• Hydrophobic environment makes H-bonding between bases stronger (no competition with water)

• Cause the sugar-phosphate backbone to twist.

View down the Double Helix

Sugar-phosphatebackbone

Hydrophobic Interior with

base pair stacking

Structure of DNA Double

Helix• Right handed

helix• Rise = 0.33

nm/nucleotide• Pitch = 3.4 nm /

turn• 10.4 nucleotides

per turn• Two groves –

major and minor

• Within groves, functional groups on the edge of base pairs exposed to exterior

• involved in interaction with proteins.

Factors stabilizing DNA double Helix

• Hydrophobic interactions – burying hydrophobic purine and pyrimidine rings in interior

• Stacking interactions – van der Waals interactions between stacked bases.

• Hydrogen Bonding – H-bonding between bases

• Charge-Charge Interactions – Electrostatic repulsions of negatively charged phosphate groups are minimized by interaction with cations (e.g. Mg2+)