Chapter 19 Nucleic Acids

1. Chapter 19 Nucleic Acids • Nucleic acids represent the fourth major class of biomolecules (proteins, carbohydrates, fats) Like other Macromolecules- contain multiple similar monomeric units covalently joined to produce large polymers Ch 19 Nucleic Acids Ch 20 DNA Replication Ch 21 Transcription and RNA Processing Ch 22 Protein Synthesis Read the chapters

2. Chapter 19 Nucleic Acids • Nucleic acids represent the fourth major class of biomolecules (proteins, carbohydrates, fats) • Genome - the genetic information of an organism Like other Macromolecules- contain multiple similar monomeric units covalently joined to produce large polymers 1889: Isolated acidic molecule from nuclei (nucleic acid) 1944: DNA is the mol that carries genetic information Oswald Avery 1953: Watson/Crick determine structure of DNA

3. 1953: James Watson and Francis Crick determine structure of DNA Feb. 28th 1953: Eagle pub in Cambridge “we have found the secret of life”

4. Information specifying protein structure F. Crick 1958: Central dogma • Informationflow: • DNA RNA PROTEIN Reverse transcriptase (retro-viruses) • Transcription - copying of the DNA sequence information into RNA • Translation - Information in RNA molecules is translated during polypeptide chain synthesis

5. Nucleotides Are the Building Blocks of Nucleic Acids • Nucleic acids are polynucleotides • Nucleotides have three components: (1)A five-carbon sugar(2)A weakly basic nitrogen base(3)Phosphate Unsaturated (double bonds) Planar and absorb UV

6. Nucleotides Are the Building Blocks of Nucleic Acids • Nucleotides have three components: • five-carbon sugar • weakly basic nitrogen base • Phosphate What type of bond?

7. Nucleotides Are the Building Blocks of Nucleic Acids Nucleic acids are polynucleotides Nucleotides have three components: A five-carbon sugarA weakly basic nitrogen basePhosphate

8. keto enol Tautomeric forms in equilibrium Amino and Lactam (keto) forms more stable and predominate

9. Fig 19.6 • Hydrogen bond sites in nucleic acids X

10. Hydrogen bond sites in nucleic acids

11. Nucleosides RNA

12. Nucleosides RNA DNA

13. Nucleotides phosphate esters of nucleosides Potential sites of phosphate: • Ribonucleosides contain three • hydroxyl groups • (2’, 3’ and 5’) • Deoxyribonucleosides can be phosphorylated at the • 3’ and 5’ positions AMP=pA ATP=pppA A nucleotide is assumed to be 5’-phosphate unless specified otherwise

14. Thymine Cytosine Guanine Purine vrs Pyrimidine Uracil Adenine

15. Thymine Cytosine Guanine Purine vrs Pyrimidine Uracil Adenine

16. Nucleoside vrs Nucleotide

17. Nucleoside vrs Nucleotide Macromolecules Tues Quiz: Know the difference between nucleoside/nucleotide, purine/pyrimidine Be able to identify and name the base structures (adenine etc) Name the nucleoside (adenosine etc)

19. Anti form predominates

20. Nucleotides joined by 3’-5’ phosphodiester linkages

21. The Free Energy of ATP Phosphoanhydride vrs Phosphoester linkage

22. Nucleotides joined by 3’-5’ phosphodiester linkages Structure of the tetranucleotide pdApdGpdTpdC Primary structure Extended conformation Long and thin Directionality 5’-3’ Backbone: phosphate and 3’,4’ and 5’ carbon and 3’ oxygen

23. DNA Is Double-Stranded Erwin Chargaff: Chargaff rules: A and T are present in equal amounts in DNA Same with G and C A=T G=C Ratio of purine/pyrimidine always 1:1 DNA is double stranded and A pairs with T (and C with G) Watson and Crick used all the data---- double helix DNA structure

24. Two Antiparallel Strands Form a Double Helix Two strands run in opposite directions Bases in opposite strands pair by complementaryhydrogenbonding Adenine (A) - Thymine (T) Guanine (G) - Cytosine (C) Equal distance between backbone (Purine/pyrimidine 1:1) Complementary:can serve as template For other strand

25. Complementary base pairing and stacking in DNA Stacking of bases Stabilizes dsDNA Cooperative non-covalent Within hydrophobic interior Helix allows effective stacking

26. Three dimensional structure of DNA • A double helix has two grooves of unequal width: major groove and minor groove • Within each groove base pairs are exposed and are accessible to interactions with other molecules • DNA-binding proteins can use these interactions to “read” a specific sequence Structure of helix allows access to info • B-DNA is a right-handedhelix, diam. = 2.37nm • Rise (distance between stacked bases) =0.33nm • Pitch (distance to complete one turn) = 3.40 nm • 10.4 base pairs per turn

27. Conformations of Double-Stranded DNA B Z A Two alternative structures to B-DNA:A-DNA (forms when DNA is dehydrated)Z-DNA (when certain sequences are present) A-DNA is more tightly wound than B-DNA, and has grooves of similar width Z-DNA has no grooves and a left-handed helix Both A-DNA and Z-DNA exist in vivo in short regions of DNA G/C rich regions dG residue: base is in Syn conformation

28. Race to determine the structure of DNA 1944 realized DNA carried genetic info DATA: Chargaff rules ; A=T and G=C 1953 Card board cut out puzzle Proper tautomeric forms of bases Evidence for helical nature What data did they collect on their own ????? Watson and Crick model 1947 Crick knew no biology, little organic chemistry or crystallography 1951 met Watson 1953 determined structure of DNA 1954 finished PhD on X-ray diffraction of proteins 1962 Nobel prize

29. Race to determine the structure of DNA 1953 Watson and Crick model 1953 “Photo 51” Rosalind Franklin Two-fold symmetry (not triple) Cross-like reflections of helix Linus Pauling----wrong !! 1953 paper incorrect triple helical model 1951 solved alpha helix Diff sizes of bases—had to be on outside Did not have good x ray data—Wilkins turned him down Did not visit Franklin 1951 same triple helical model thrown out by W/C Rosalind tore it apart…it ignored her data How to pack neg charge in center? 10x more water in molecule than the model would allow

30. Rosalind Franklin Dies 1958 (ovarian cancer) Nobel prize 1962

31. Linus Pauling----wrong !!