Question

1. Given that Dr. Bleu appears to have been killed by an inhibitor to XYZase, there is now sufficient cause to search the labs of Drs. Greene, Ploum, and Mustard so that you can recover and test samples of the compounds they are each developing. You interview each suspect and learn that XYZase is a 547 kDa protein with an N-terminal regulatory domain and a large C-terminal catalytic domain that contains the enzyme’s active site. Each suspect also describes how their inhibitor works with respect to XYZase. Use the interviews below to answer the following questions-

Dr. Greene- Dr. Greene works on an inhibitor of XYZase that acts by binding an Asp residue in the N-terminal domain of XYZase. She has solved crystal structures which reveal that the inhibitor can bind to this site both in the presence and absence of substrate.

Dr. Mustard- Dr. Mustard is studying a compound that binds to a site on the protein approximately 40 angstoms away from the active site. He has solved crystal structures of XYZase with and without its substrate bound. Data from these structures show an α-helix blocks the inhibitor binding site when substrate is not bound to XYZase. The binding of substrate to XYZase results in a conformational change that shifts this α-helix to allow the inhibitor to bind.

Dr. Ploum- Dr. Ploum is studying the effects of a molecule that mimics the structure of XYZase substrate, Compound A. She has solved crystal structures that confirm the inhibitor binds non-covalently in the active site, as expected.

a. What type of reversible inhibitor is Dr. Greene studying?

b. What type of reversible inhibitor is Dr. Mustard studying?

c. What type of reversible inhibitor is Dr. Ploum studying?

2. Which scientist is the murderer? Explain how you drew this conclusion.

Answer 1

Dr. Greene is studying the uncompetitive type of reversible inhibitors as his inhibitor can bind to the enzyme in presence or absence of substrate.

Dr. Mustard is studying Non-competitive type of reversible inhibitor as the inhibitors bind to the site other than the substrate binding site

Dr. Ploum is studying the competitive type of reversible inhibits as his inhibitors compete with the substrate for active site

B- Dr. Greene is the murderer. All the other type of inhibition can be overcome by adding more substrate but not the inhibitors that Dr. Greene has designed.