Chapter 8

Nucleotides and Nucleic Acids

Part 1

Nucleotides and Nucleic Acids

Learning Goals
Biological function of nucleotides and nucleic
acids
Structures of common nucleotides
Structure of double-stranded DNA
Structures of ribonucleic acids
How Proteins bind to DNA

Functions of
Nucleotides and Nucleic Acids
Nucleotide Functions:
Energy for metabolism (ATP, GTP, CTP,
UTP)
Enzyme cofactors (NAD+, NADP+, FAD)
Signal transduction (cAMP, cGMP)
Nucleic Acid Functions:
Storage of genetic info (DNA)
Transmission of genetic info (mRNA)
Processing of genetic information
(ribozymes)

Nucleotides and Nucleosides

Nucleotide =
Nitrogeneous base
Pentose
Phosphate
Nucleoside =
Nitrogeneous base
Pentose
Nucleobase =
Nitrogeneous base

N-Glycosidic Bond
In nucleotides the pentose ring is attached to
the nucleobase via N-glycosidic bond
The bond is formed to the anomeric carbon of
the sugar in configuration
The bond is formed:
to position N1 in pyrimidines
to position N9 in purines
This bond is quite stable toward hydrolysis,
especially in pyrimidines
Bond cleavage is catalyzed by acid

Modified Nucleotides

Modified Nucleotides - More

Chemical Instability of RNA at

Alkaline pHs

UV Spectrum

ds DNA

ds DNA on
the English 2
Pound Coin

Watson and Crick Had Three Sets of

Data
1. Rosalind Franklins X-ray crystallography
2. Chargaffs Rules
3. Chemical Structures of Nucleotides

Rosalind Franklins X-ray Crystallography

Some of Chargaffs Rules

1. DNA base composition varies between species.
2. DNA from different tissues of same species has
the same base composition.
3. Base composition of a species does not vary with
age, nutritional state, or change in environment.
4. No matter what species A = T and G = C and
[purines] = [pyrimidines] which is A+G = T+C

Erwin Chargaff in the 1940s worked out methods

to measure each nucleotide in DNA. The rules
made sense when applied to the Watson-Crick
DNA structure.

DNA Bases Pairing

Suppose you isolated DNA from two unidentified
species of bacteria: species X and species Y.
You know that adenine makes up 32% of species X
DNA and 13% of species Y DNA.
How much of each nucleotide are present in these
two DNAs?

One species was isolated from a hot thermal spring,

which is the most likely one?

The Watson-Crick Structures

The Beauty of the

Watson-Crick
Structure was that
it gave a way to do
Hi-fidelity
Replication

DNA is not necessarily straight, and

it can bend.

Most DNA is in the anti-conformation

DNA can From Three Types of

Helices

Forces that hold two ssDNA dsDNA

1. H-bonds and 2. hydrophobic stacking
About equal in strength..look at the diagrams,
wheres the water?

DNA Helix Forms

Looking Down the DNA Helix

How Long is Your Book Laid Page by Page?

Lehninger 5th Edition is 1,263 printed pages + a few
blanks
pages are 21.5 cm wide x 27.5 cm high.
Placing the pages next to each other then the book is How
Long?
Answers = 271.5 meters side by side .. or
347.3 meters tops to bottoms
or in Sports terms:
About 2.7 to 3.5 and football fields long.
NOW
EOC Problem 3: How long is your DNA? The
average human has about 0.5 g DNA. The B-helix
weighs about 10-18 g/1000 nucleotide pairs. What

B-Z Junctions
How to Go from Right Handed to Left
Handed

Ha, et al. 2005. Crystal structure of

a junction between B-DNA and ZDNA reveals two extruded bases.
Nature. 437:1183-1186.
Samsung Biomedical Research
Institute, Seol, Korea
and Massachusetts Institute of
Technology, Cambridge, MA.

B-Z Junctions an AT pair flipped

inside out.

B-Z Junction Side View

Z DNA is a higher energy form of the double helix

stabilized by negative supercoiling (generated by
transcription or unwrapping from nucleosomes).
Z DNA near the promoter stimulates transcription.
Stabilized by proteinsKd in nM range.
Butcan relax back to the B helix.
Extruded bases may be site for DNA modification.

DNA Binding Proteins Its all in the

Grooves

EOC Problem 1 looks at H-bonding from the sides of the

DNA strand..through the grooves.

Proteins that Bind DNA Showing Major

Groove

Helix Turn Helix Motif Bacterial Lac

Repressor

Lac Repressor (grey) Bound to DNA (blue)

Minor Groove
is Also
Important
Minor Groove
narrowing with AT
tracts variation
in shape.
Enhances Arg
Binding

Rhosetal.Nature461:12482009

Things to Know and Do Before Class

1. Structure and chemistry of the nucleotides.
2. Essence of Chargaffs Rules.
3. Structure and properties of the dsDNA and dsRNA
helices.
4. BZ junctions.
5. How proteins bind to DNA.
6. EOC Problems: 1-3