1. Proteins: Amino Acid Chains DNA Polymerase from E. coli Standard amino acid backbone: Carboxylic acid group, amino group, the alpha hydrogen and an R group (L)-alanine, the natural form

2. Importance of Chirality in Biological Systems (L)-thalidomide is an effective sedative for expectant mothers while (D)-thalidomide causes severe birth defects (L)-

3. Hydrophobic Amino Acids Non-polar side chains that interact very weakly with water. What type of bonding forces might contribute significantly for these AAs?

4. Polar Amino Acids Where might these AAs be located in a polypeptide? Amino acid side chains readily interact with water

5. Charged Amino Acids Always charged under physiological pH What is the predicted pKa values for these acids and bases?

6. Ionizible Amino Acids at Physiological pH Values Cysteine (Cys) Histidine (His) Imidazolium ion Thiol group Are these oxidation/reduction reactions? Thiolate anion

7. pK a Values of Ionizable Amino Acids ca. pK a 3 4 6 8 9 10 12

8. Disulfide Bond Formation Polypeptide stabilization Oxidation/reduction reaction

9. Amino Acid Coupling via Dehydration Synthesis What is the Nucleophile, Electrophile and Leaving Group in this reaction?

10. Levels of Polypeptide Organization

11. A polypeptide Primary Structure: Amino Acid Order or Sequence Coding convention: N- to C-terminus from left to right

12. Bond Length Indicates a Hybrid Bond Number of ca. 1.5 C-N single bond 1.45 Å C=N double bond 1.25 Å Peptide resonance

13. Peptide Bond Forms a Planar Unit Steric hindrance favors trans configuration

14. Rotation in a Polypeptide Restricted to the Cα Phi Psi

15. Ramachandran Diagram Shows Permitted Angles in Green - 60 +120 What is phi and psi?

16. What is the environmental condition favorable for a polypeptide to form an alpha helix? Where in the polypeptide would an α-helix be located? α-Helix is a Coiled Polypeptide: Secondary Structure

17. Hydrophobic Strip Formed on the Surface of alpha- Keratin

18. n + 4 Hydrogen-Bonding Scheme for an Alpha Helix

19. Ribbon Depiction of Ferritin: an Iron Storage Protein

20. Beta-Sheet Polypeptide: Secondary Structure Antiparallel Parallel Which configuration would be more stable ?

21. Is the distance of 7 Å reasonable? What do the green spheres represent? What is the green spheres orientation relative to the β-sheet? What is a favorable environment for beta-sheets formation? Beta-Sheet Backbone

22. Beta-Sheet Configurations: Super-Secondary Structure Twisted-Sheet Beta-BarrelReverse Turn

23. CD4 Surface Protein in HIV with Four Similar beta-Sheet Domains

24. Alpha-Helix Configuration: Super-Secondary Structure Common motif in DNA-binding proteins

25. Overall Configuration of a Single Polypeptide: Tertiary Structure Oxygen Transporter in Muscles: Myoglobin

26. Polypeptide Amino Acid Distribution: charged (blue), hydrophobic (yellow) & other (white) Space-Filling Model of Myoglobin Cross-Sectional ViewSurface

27. Overall Configuration of Multiple Polypeptides: Quaternary Structure Ball and Stick Ribbon Representation α-Keratin – primary component of wool, hair and nails Parallel alpha double helix with 7 AA 1,4 hydrophobic strip Rich in cysteine residues that can form disulfide bridges 2 right-handed double helices coil in an anti-parallel fashion to form a left-handed super-helix: a coiled-coiled protein Length of ca.1000 Å What causes the hardness of the fibrous protein keratin?

28. Hydrophobicity Scale Free energy change in transferring from an organic to aqueous solution

29. Hydrophobic Effect In Protein Folding Minimizing H 2 O-nonpolar interactions

30. Protein Folding by Progressive Stabilization of Intermediates All conformations are not sampled Exergonic process Hydrophobic interactions a major driver Chaperonin-assisted protein folding

31. Chapter 4 Problems: 1-5, 7, 10, 11, 12, 13, 23, 29, 35, 37, 51, 55 and 57