BIBC 100 / Structural Biochemistry
In the Class Reader please
read chapter 1.1 on water structure, molecular dipole moment, hydration
shells, and the hydrophobic effect.
1. What molecular properties determine the solubility of polar molecules in water?
2. Which type of non covalent interaction is involved in the presence of hydrogenated oxygen, nitrogen, but not carbon atoms?
3. Which amino acid residues should you avoid when designing a mono disperse, water soluble peptide?
4. How does your amino acid selection differ from the previous question if asked to design a signal sequence peptide?
5. How many amino acids do you need in a peptide to span a distance of 30 Angstroms in alpha helical conformation ( a so called transmembrane spanning alpha helix)?
6. Which high resolution structure technique can be used to determine if a hair-pin motif consists of antiparallel, parallel, or both types of beta sheet structures? Explain which structural property of a beta sheet allows this distinction. What would you find in a protein with a jelly role motif?
7. Describe the process and driving force of an alpha helical bundle formation in aqueous solution.
8. What stabilizes the supramolecular structure of a phospholipid membrane? Define the interior of the membrane with the dielectric property of the system. What does 'amphipathic' mean, and how does this property relate to the stability of membranes?
9. Why do protein units in a protein crystal need to be ordered? Why is ordering not necessary for protein solutions during NMR analysis?
10. Describe the water structure around a:
a)Na+ ion
b)oil droplet
11. Describe the quaternary structure of a B-DNA oligonucleotide. What GC content would you expect if this oligonucleotide is designed to bind TBP (TATA box binding protein)?
12. What is the structural principle of a leucine zipper; what general feature of an alpha helix does it follow?
13. Explain the function of Zn++ ions in Zn-finger proteins.
14. What is the importance of having regions of high variability, like the CDR, on antibodies? On T-cell receptors?
15. How can the X-ray structure of the immunoglobulin fold of a variable domain help us understand why the CDR regions don't compromise the overall stability of the Ig domain (compare this problem to the non related structures found in the chymotrypsin superfamily of serine proteases)?
16. What biochemical 'trick' was needed to solve the X-ray structure of immunoglobulins?
17. Which of the following protein(s) is not a membrane protein: class
I MHC, T-cell receptor, IgG, IgM, muscarinic Acetylcholine Receptor, Myoglobin?
18. Discuss the location of amphipathic helices on the surface of proteins/at the center of ion channel complexes like the nicotinic acetyl cholin receptor?
19. Ion channels can be compared to enzymes, even though they do not catalyze a chemical reaction. Describe the 'catalytic' mechanism of a ligand gated ion channel.
20. Explain the allosterism of the nicotinic acetylcholine receptor.
21. Bacterial porins contain 16 anti-parallel beta strands that form a beta barrel pore structure. What could you say about the distribution of amino acids along the sequence that stabilize the barrel in membranes while allowing ion flux across the membrane?
22. Why is the helix of gramicidin A called a beta helix? What is unusual about its amino acids?
23. What are the major core monosaccharide constituents of an N-linked oligosaccharide?
24. You study a new plasma membrane protein and predicted 7 potential transmembrane spanning helices. Based on the amino acid sequence analysis, how could you predict the inside-to-outside orientation of the protein, i.e., if the N-terminal domain is extra- or intracellular? To which superfamily of proteins does the new protein likely belong?
25. What is the mechanism of lectin binding to other proteins? Can it bind any kind of protein?
26. Cadherins are one type of protein receptor family involved in cell-cell interaction. Explain all potential analogies to the PDGF receptor based on their domain structure and function.
27. How does a cell recognize if a newly synthesized protein has to be processed by the endoplasmatic reticulum proteins?
28. Which redox molecule in the photosynthetic reaction center couples
electron and H+ transport?
29. What biological role(s) distinguishes Ca++ ions from other (divalent) metal ions? (Use roles discussed in this class only).
30. A Hill plot is used to determine if a protein shows cooperativity between subunits or not. How do you determine the Hill constant from the plot and how would the curve for a non-cooperative enzyme complex look like? Draw a Hill-plot for an enzyme with negative cooperativity.
32. How do the T and R conformation of the hemoglobin quaternary structure
support a symmetric model of allostery?
33. Explain the name 'serine/aspartate/cystein protease' (consult the chapter on the HIV protease for aspartate proteases).
34. What are the basic concentration conditions of enzyme and substrate needed to determine ½Vmax of enzymatic catalysis? What is the substrate concentration called at ½Vmax?
35. You analyzed amino acid composition of the specificity pocket of a new type of serine protease and found lysine at the bottom of the pocket. What is your prediction about the sequence specificity of the protease?
36. How can a protease inhibitor be a potential drug suppressing the
proliferation of HIV but not affect the host physiology?
37. Why are cystein residues in globular proteins advantageous for the study of protein folding pathways in vitro?
38. The melting curve of a protein shows a sigmoidal transition from the native fold to the unfolded conformation. What is the mechanism behind this type of curve?
39. What is the driving force of self-assembly systems / protein-folding in water?
40. Thermal motion is important in enzymatic activity? Explain.