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Exploring Nucleic Acid Structures

Exploring Nucleic Acid Structures . Nucleic Acid Building Blocks: Nucleotides. Base. Sugar. Phosphate. Bases. Pyrimidines and purines Positions of hydrogens key to recognition. DNA vs. RNA. Bases Purines and Pyrimidines Bases in DNA (dA, dT, dG, dC) Bases in RNA (A, U, G, C) Sugars

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Exploring Nucleic Acid Structures

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  1. Exploring Nucleic Acid Structures

  2. Nucleic Acid Building Blocks: Nucleotides Base Sugar Phosphate

  3. Bases • Pyrimidines and purines • Positions of hydrogens key to recognition

  4. DNA vs. RNA Bases Purines and Pyrimidines Bases in DNA (dA, dT, dG, dC) Bases in RNA (A, U, G, C) Sugars DNA has deoxy ribose sugar RNA has ribose sugar deoxy-ribose ribose

  5. Tautomeric structures • Keto vs inol • Different hydrogen bonding patterns

  6. pK of nucleotides • Affects hydrogen bonding possibilities N1 adenine-3.5 N3 cytosine-4.2 N7 of adenine 1.0

  7. Watson Crick Base Pairs Geometry of A:T and G:C base pairs are isosteric

  8. Diversity of hydrogen bonding geometries

  9. Hydrogen bonding if WC base pair • Definition of Major and Minor groove • Mechanisms of recognition

  10. Basepair-base • C-G-C (C must be protonated) • T-A-T normal • Found in triple helices

  11. Amino acid - base pair

  12. Amino acid - base pair

  13. Amino acid - base pair

  14. Amino acid - base pair

  15. Base morphologyPropeller twist

  16. buckle

  17. Base pair twist

  18. roll

  19. Backbone conformation

  20. Anti vs. syn

  21. Change in sugar conformation affects the backbone

  22. Ribose ring is never flat

  23. C4’-C5’-g+

  24. Conformation wheel for nucleotides • -3 values • -3 values • -3 values • -two ranges • C3’ endo • C2’ endo • -trans,g- • -3 values

  25. Common building blocksSmall changes leading to big differences

  26. ds DNA types B-DNA A-DNA Z-DNA

  27. Polymer Characteristics

  28. Canonical DNA structures

  29. A DNAB DNA

  30. B-DNA

  31. B DNA View down helix axis

  32. Space filling B DNA

  33. A DNA

  34. A DNA

  35. References Saenger, Wolfram. Principles of Nucleic Acid Structure. Springer-Verlag New York Inc., 1984, pp. 109, 113. Neidle, Stephen. Nucleic Acid Structure and Recognition. Oxford University Press, 2002, pp. 18, 21-22, 34, 36, 68, 90, 165-166. Voet, Donald and Judith G. Biochemistry. John Wiley & Sons, 1990, pp. 792, 797, 807-809.

  36. Defined sequence DNA CGCGAATTCGCG • High propeller in center • Narrow minor groove

  37. Spine of hydration

  38. Defined sequence A DNA

  39. Z DNA • Left handed • Very deep minor groove • Major groove on outside Voet, Donald and Judith G. Biochemistry. John Wiley & Sons, 1990, p. 802.

  40. Defined sequence CGCGCG

  41. Z DNA-2 nucleotide repeat

  42. Mismatches • Local changes • Global structure same as parent

  43. PNA Triple strand • DNA strand + Peptide nucleic acid sequence

  44. Quadruplex DNA

  45. G pairing in quadruplex

  46. Diversity of folds • Two different dimer folds • Also possible • Single strand • Four strands

  47. Holliday junction formed by 4 decamer strands

  48. 4 way junction

  49. RNA-DNA complex with a junction structure

  50. References Neidle, Stephen. Nucleic Acid Structure and Recognition. Oxford University Press, 2002, pp. 33-36, 76-77, 83, 97. Voet, Donald and Judith G. Biochemistry. John Wiley & Sons, 1990, pp. 796, 799, 800, 802.

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