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Biochemistry 430/530 Andrew MacMillan andrew.macmillan@ualberta MedSci 4-39 (by appointment)

Biochemistry 430/530 Andrew MacMillan andrew.macmillan@ualberta.ca MedSci 4-39 (by appointment) 492-3813 http://www2.biochem.ualberta.ca/MacMillanLab/ “Course Notes”. Medicine/Physiology. Chemistry. Szostak, Greider, Blackburn. Steitz, Ramakrishnan, Yonath.

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Biochemistry 430/530 Andrew MacMillan andrew.macmillan@ualberta MedSci 4-39 (by appointment)

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  1. Biochemistry 430/530 Andrew MacMillan andrew.macmillan@ualberta.ca MedSci 4-39 (by appointment) 492-3813 http://www2.biochem.ualberta.ca/MacMillanLab/ “Course Notes”

  2. Medicine/Physiology Chemistry Szostak, Greider, Blackburn Steitz, Ramakrishnan, Yonath 2006 Andrew Z. Fire, Craig C. Mello 1993 Richard J. Roberts, Phillip A. Sharp 1989 Sidney Altman, Thomas R. Cech

  3. Classical Gene Regulation

  4. 1) RNA Structure/Reactivity (1) 2) Ribozymes/Riboswitches(2) 3) pre-mRNA Splicing (3) 4) RNA Degradation/RNAi(2)

  5. RNA information structure function

  6. Central Dogma

  7. Central Dogma

  8. Central Dogma

  9. RNAi (siRNA, miRNA)

  10. Hammerhead Ribozyme

  11. Ribosome - Large Subunit H. marismortui -2833 nt -27 proteins Science (2000) 289:920-30

  12. Chemistry Review!

  13. RNA Structure and Reactivity 7 6 5 1 8 4 2 9 5’ 3 4’ 1’ 2’ 3’ 4 3 5 6 2 1

  14. Nucleic Acids Chemical Functionalities -Hydrogen Bonding -Metal Coordination -Acid/Base -Nucleophilic Reactions

  15. Hydrogen Bonding ~3-5 kcal/mol D A

  16. Hydrogen Bonding ~3-5 kcal/mol (excluding entropy - how much is this worth?) D A

  17. Metal Coordination Na+, K+, Mg2+, Mn2+

  18. Acid/Base

  19. Acid/Base pKa ~ 12 pKa ~ 14

  20. Nucleophilic Reactions I

  21. Nucleophilic Reactions I

  22. Nucleophilic Reactions II

  23. B-Form DNA Dickerson and coworkers

  24. A-Form RNA

  25. Base-Pairing in RNA Watson-Crick Hoogsteen

  26. Base-Pairing in RNA Major Minor Watson-Crick Hoogsteen

  27. Higher Order Structure in Nucleic Acids From Non-WC Base-Pairs

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