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- The complete OWLS solutions set: OWLSsolutionstoallproblems.pdf
- Final review session TODAY led by En-wei in CS24 from 3-4:20pm- Final Exam:
- - Each part is worth 100 points and you will have a total of 3 hours to complete both parts (you can work on them in any order you choose, or go back and forth between them).
- - Part A will cover all the "new" material since Midterm 2.- - Part B will be comprehensive and will cover the
entire course. Practice on old exams! http://www.chem.ucla.edu/harding/14C/14C_s12/14C_s12_syl.html#exams
- Your final exam will be on Wednesday, June 13 from 8-11am.Last name A-C: Please go to Young 2200Last name D-Z: Please go to CS50
- You may use your model kits! You will be provided with all the information you were given on Midterm 1 and Midterm 2
Biomolecules Survey Part 4: Nucleic AcidsLecture Supplement page 248
Early History
1869: Friedrich Miescher isolates “nuclein” from white blood cells
Phosphoric acid
O
PHO
OH
OH
Heterocyclic baseHeterocycle: Has a least one ring which includes an atom other than carbon
Pyrimidines Cytosine (C) Thymine (T) DNA Uracil (U) RNA
Purines Adenine (A) Guanine (G)
N
N
N
NN
N
H
N
N
H
O
NH2
N
N
H
O
O
H3C H
N
N
H
O
O
H
N
NN
N
H
H
O
NH2N
NN
N
H
NH2
Early 20th century: Nuclein found to consist of three fundamental components
X = OH, D-riboseX = H, 2-deoxy-D-ribose
CHO
CH X
CH OH
CH OH
CH2OH
Adenosine (a nucleoside)
O
XHO
HO
N
NN
N
NH2
Nucleosides and Nucleotides
1920’s: Carbohydrate + heterocyclic base = nucleoside
•Heterocyclic base nitrogen bonded to ribofuranose anomeric carbon
•Carbohydrate = ribose (X = OH) in ribonucleic acid (RNA)
= deoxyribose (X = H) in deoxyribonucleic acid (DNA)
•Nucleoside + phosphoric acid = nucleotide (nucleoside with phosphate on 3' or 5' carbon)
Adenylic acid (a nucleotide)
orO
XHO
O
N
NN
N
NH2
PHO
O
HO
O
XO
HO
N
NN
N
NH2
P
O
HO
HO
1'2'3'
4'
5'
DNA is a Polymer1939: DNA is a polymer of many nucleosides linked by 3', 5'-phosphodiesters
•1957 Nobel Prize in Chemistry to Lord Alexander Todd "for his work on nucleotides and nucleotide co-enzymes" (nobelprize.org)
•Nucleotide sequence = DNA or RNA primary structure (compare protein primary structure)
OOP
O
O
O
O
O
OP
O
O
O
N
NN
N
NH2
N
NH
O
O
H3C
OOP
O
O
O
O
OP
O
O
O
N
NN
N NH2
H
O
N
N
NH2
O
5' end
3' end
DNA Carries the Genetic Code
Before 1944: Proteins believed to carry genetic information
DNA is not much more than a biological curiosity
1944: DNA demonstrated to be the cellular molecule that carries genetic information:
Avery, Macleod and McCarty: Studies on the Chemical Nature of the Substance
Inducing Transformation of Pneumococcal Types: Induction of Transformation by a
Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III, Journal of
Experimental Medicine, 1944, 79, 137-158.
After 1944: DNA is the hot topic in biology
Chargaff's Rules1950's: Erwin Chargaff studies heterocyclic base ratios in DNA from various organisms
Chargaff's Rules: In DNA of all organisms...
Species G A C T (G+A)/(C+T) A/T G/C
S. aureus 21.0 30.8 19.0 29.2 1.11 1.05 1.11
E. coli 24.9 26.0 25.2 23.9 1.08 1.09 0.99
Wheat germ 22.7 27.3 22.8 27.1 1.00 1.01 1.00
Bovine thymus 21.5 28.2 22.5 27.8 0.96 1.01 0.96
Human thymus 19.9 30.9 19.8 29.4 1.01 1.05 1.01
Human liver 19.5 30.3 19.9 30.3 0.98 1.00 0.98
•Base ratios random in RNA
•G/C ratio ~1:1
•A/T ratio ~1:1
•(G+A)/(C+T) = (purines)/(pyrimidines) ratio ~1:1
The Problem Solved1953:
} Not compatible with single helix
•James Watson and Francis Crick combine...Franklin's x-ray dataChargaff's rulesExamination of molecular models
} DNA is a base-paired double helix
•Rosalind Franklin: X-ray studies of DNA show helical structureDiameter = 20 ÅLength = 34 Å per 360o turnCalculated density
Watson and Crick made extensive use of models to study molecular structure. Follow their example!
Franklin's Photo 51. The X pattern is characteristic of a helical structure
= secondary structure of DNA
Watson-Crick Base Pairs
•Heterocyclic bases associate via two or three hydrogen bonds
Adenine-ThymineN
N
N
N
H N
N
N H O
deoxyriboseO
deoxyribose
H
CH3
Guanine-CytosineN
N
N
N
H N
N
HN
O H N
H
deoxyriboseO
H
deoxyribose
•Base pairs similar size and shape efficient packing into double helix
same size
Based-Paired Double Helix
DNA strands are antiparallel
Space-filling model: Atoms represented at their van der Waals radii (electron cloud volumes)
sugar-phosphatebackbone
minorgroove
majorgroove
360o turn
~10 base pairs
34
Pi stacking5' end 3' end
3' end 5' end
Hydrogen bondseasily disassembled
Strong
Based-Paired Double HelixPublication: Watson and Crick, Molecular Structure of Nucleic Acids: A Structure for
Deoxyribose Nucleic Acid, Nature 1953, 171, 737-738
"It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."
"We have also been stimulated by a knowledge of the general nature of the unpublished experiment results and ideas of ... Dr. R. E. Franklin..."
1962 Nobel Prize in Physiology or Medicine: to Wilkins, Watson, and Crick "for their discoveries concerning the molecular structure of nuclear acids and its significance for information transfer in living material"
Optional reading: The Double Helix: A Personal Account of the Discovery of the
Structure of DNA (Watson)
The DNA Space Problem•Human genome = 3 x 109 base pairs (bp)•(3 x 109 bp) x (34 Å per 10 bp) x (10-10 m per Å) = ~1 meter in length
•Solution: DNA tertiary structure = supercoiling
Memorize DNA Structure?
CTGGAAGTACGTCTA
Leu LeuGlu Val Arg
LeuTTA TTG CTACTT CTC CTG
CTAGAAGTACGTCTT
Something
Something Alive
Something Alive (and complex!)
Origin of Universe
Origin of Life Variations
of Life
Nothing