MBB 222 Study Guide - Midterm Guide: Protein Folding, Hydrogen Bond, Equilibrium Constant

Some proteins, once folded “associate” to form higher order structures (i.e., quaternary structure). Within these structures the single protein chain is known as a “subunit” (not to be confused with a protein domain). If two identical protein chains fold and associate, the quaternary structure is named “homodimer” (and the individual subunits are sometimes referred to as “monomers”); for three “homotrimer” and so on. If, on the other hand, the two protein chains that associate have different primary structures, the quaternary structure is named “heterodimer”. Using the dimer as an example, we know that the respective regions of the protein subunit surfaces that are interfaced, are responsible for the “favorable energy of interaction” which stabilizes the dimeric protein complex.

(a). Although, noncovalent bonding interactions are used both for stabilization of the folded protein molecule and its dimerization, the contribution of the “hydrophobic effect” to chain folding is significantly greater than its contribution to subunit association. Define the “hydrophobic effect” and explain why you would expect it to have a more pronounced role in chain folding compared to dimerization of the folded molecules.

(b) As the protein chain folds to the native structure, it loses entropy. Upon dimerization, more protein entropy is lost. Compare and contrast the source of protein entropy loss, which occurs with folding, with that which occurs with dimerization.

Problem A: This is a very simpllistic approach to protein folding, which ignores solvent and volume effects, but it allows us to practice what we have learned about thermodynamics and kinetics. Enzymes are long chains of amino acids that have to fold in the proper way so as to exhibit enzyme activity. They can catalyze certain reactions. Let us pick a reaction in the human body at 37 C, we will call it enzyme X.

1) What is the expected sign of delta G for the reaction that forms enzyme X starting from the long chain of amino acids at 37 C?

2)What is the value of K(eq) for the reaction at 37C, assuming the system is reversible?

3)Based purely on the drawing (unfolded and folded (native form)) what is the expected sign of delta S for the reaction that forms enzyme X at 37 C?

4)What is the expected sign of delta H for the reaction that forms enzyme X at 37 C?

5) Under what conditions is the folded form NOT thermodynamically favored? always favored, high temperatures, never favored, low temperatures

6)Let's say that enzyme X is the catalyst responsible for breaking starch down to individual glucose molecules. What of the following things can happen to the starch and enzyme system if you rainse the temperature?

a-the rate of the reaction of starch going to glucose will increase

b-nothing should happen since a catalyst does not affect the equilibrium

c-the enzyme could stop working effectively becauset the folded form would stop being made and would start to unravel if the process is reversible

d-the equilibrium constant will get bigger to favor the glucose side more.