NUCLEIC ACID STRUCTURE
Nomenclature
The two types of bases:
purine = short name = large base = adenine and guanine
pyrimidine = long name = small base = uracil, thymine and cytosine
A nucleoside = base + sugar
purine = adenosine and guanosine
pyrimidine = cytidine, uridine, thymidine
A nucleotide = base + sugar + phosphate
In polymerized form:
polynucleotides (many) oligonucleotides (few)
Primary structure
Polynucleotides have two important features: direction and sequence
The base sequence is the carrier of cellular information (what, when, and how much of catalytic, regulatory, and structural and proteins to make)
How to make the bond? What type is it?
DG of hydrolysis of a nucleotide bond = - 25 kJ/mol (vs. - 31 for ATP)
its spontaneous hydrolysis is very slow (i.e. the bond is metastable) in the absence of catalyst
this enables scientists to recover DNA from insects preserved in amber (thousands of years old)
polymerization of nucleosides into DNA results from the removal of water between phosphate (acid) and ribose (alcohol) to produce the bond.
How does this occur biochemically? Cells use NTP's + enzymes
x NTP's ---> ologonucleotides + x PPi -----> 2x Pi (DG = - 31 kJ/mol)
Direction, 5' ---> 3' , comes from the numbering of the sugar ring.
5' ACGTTA 3'
Secondary structure/Watson-Crick
History of DNA:
Miescher --> Griffith (pneumococci) ---> Avery, MacLeod, and McCarty --->
Chargaff ---> Watson and Crick ---> Hershey and Chase
Story of the Double Helix
What was the situation in 1952 when this new model was developed? What other models were under consideration? What were the novel contributions of Watson and Crick?
Chargaff's rules, which had been published in 1950, and said that A = T and G = C
1. Pauling and Corey (American) had proposed a model of 3 chains, with
phosphates to the middle
2. Fraser - 3 chains, bases hydrogen-bonded
3. Furberg - bases inside, sugar + phosphate outside
Watson and Crick (after seeing X-ray data of Rosalind Franklin) drew structure on napkin in pub (Genentech started in a similar manner)
Their model:
1. Two polynucleotide chains are coiled around a common axis (from X-rays) and running in opposite directions
2. Bases on inside of helix - sugar phosphates outside
3. 10 residues per turn of helix = 0.34 nm/base pair
4. Base pairing: A(a purine) with T (a pyrimidine), and G(purine) with C(pyrimidine), from Chargaff
5. Sequence of bases not restricted and carries the genetic information.
Recognition of the specificity of hydrogen bonding between the bases was one of the most important contributions of Watson and Crick's model to the understanding of the functioning of DNA.