Some of the following four amino acids : alanine, arginine, histidine, aspartic acid would provide a side chain for acid-base catalysis at physiological pH (assume pK of each amino acid is equal to pK value for the free amino acid in solution). Explain for each amino acid how and why each would or would not provide the side chain residue to support acid-base catalysis at physiological pH.

What is the first thing that must occur in order for the catalysis of the peptide bond to begin. What is a specificity pocket? What are the preferences of chymotrypsin due to its specificity pocket?

The enzyme creatine kinase catalyzes the ATP-dependent phosphorylation of creatine. Propose a mechanism for the reaction described using the curved arrow convention. Show the complete structure of the nucleotide.

Consider the reaction for assembly of a tetrapeptide from four amino acids: Serine + Proline + Alanine + Methionine ----> SPAM tetrapeptide Draw a free energy diagram for this reaction (you know, the one that is a line with a speed bump on it?). Remember to always label the axes on graphs, and label where the (actual) reactants and products free energies are on the curve. In addition, label activation energy and draw a dashed line showing the effect of an enzyme on the curve.

Patients suffering from sickle cell anemia have a mutation in the gene that codes for one of the hemoglobin chains, in which a single glutamate is replaced by a valine. Propose an explanation for why this substitution has such a striking effect on protein structure and function with explanation.  Suggest two other amino acids that would be less likely to cause such serious impairment of hemoglobin function if each was substituted for glutamate. Briefly explain your answer.

Compare and contrast the biological roles of the following amino acids the following pairs ofamino acids. Once you have documented these role state which member of the pair is most important and why.

This image is showing the conformations of ubiquitin superimposed. What do the structures in this figure tell us about the dynamics of enzymes? Discuss the limitations of crystal structures in the analysis of proteins. What are the benefits? What are the advantages of NMR structures?

A cytosolic protein has an important alpha amino group. The pKa of this group is approximately 8 when exposed to water outside of a protein. 1. What would happen to the pKa if this group was instead buried in the hydrophobic interior of the protein? Explain. 2. Let’s say in the hydrophobic interior of the protein, the group forms an ionic bond with a carboxylate group of the side chain of a charged Asparagine residue. How would the pKa of this alpha amino group compare with the pKa of the alpha amino group in the hydrophobic interior of the protein without a nearby Asparagine residue to form this ionic bond? Explain.

A family of proteins known as cupredoxins contain a single redoxactive Cu ion coordinated by a Cys, a Met, and two His residues. The reduction potentials of cupredoxins range from about 0.15 V to 0.68 V. What does this information reveal about the role of the protein component of the cupredoxins?

Consider a protein with two surface-exposed histidine residues: HisA is a “typical” histidine residue with a pKa = 6.2 HisB is involved in a stabilizing interaction (His-NH+ ..... -O2C-Glu) with a neighboring glutamic acid residue. For HisB, the Gibbs free energy of deprotonation at pH = 7.0 and T = 293K is ΔG'o = +15 kj mol-1. If you had a solution, at pH = 7.0 and T = 293K, containing this protein: a) What fraction of HisA residues are protonated? b) What fraction of HisB residues are protonated? c) What is the pKa of HisB?