A current problem in modern medicine is the development of drug resistance mutations. This occurs when a mutation arises in a disease-causing microbe making it resistant to a drug and thus rendering the drug useless in treating a specific disease. Many useful drugs are competitive inhibitors of specific enzymes, and the drug-resistance mutations prevent the binding of the drug. These types of mutations, in addition to preventing competitive inhibitor binding, can also sometimes reduce the activity of the enzyme. Why is that the case?

Question

A.  Binding to the competitive inhibitor is essential for the function of the enzyme
B.  These mutations most likely affect an allosteric site on the enzyme
C.  These mutations lower the activation energy of the reaction catalyzed by the enzyme
D.  These mutations most likely change the shape of the active site of the enzyme

Clarify Question
What is the key concept addressed by the question?
What type of thinking is required?

  Gather Content
  What do you already know about enzymes and how their activity is regulated? How does this drug affect enzyme activity under normal circumstances? What other information is related to the question?

  Choose Answer
Do you have all necessary information to analyze how drug resistance would reduce enzyme activity?  

  Reflect on Process
Did your problem-solving process lead you to the correct answer? If not, where did the process break down or lead you astray? How can you revise your approach to produce a more desirable result?

Answer 1

D.  These mutations most likely change the shape of the active site of the enzyme

Clarify Question
What is the key concept addressed by the question?
        · The question asks you ascertain how drug resistance development in bacteria is related to reduced enzyme activity.   
What type of thinking is required?
        · You are being asked to break down, or analyze, a possible means by which drug resistance in bacteria might work to reduce enzyme activity.   

  Gather Content
  What do you already know about enzymes and how their activity is regulated? How does this drug affect enzyme activity under normal circumstances? What other information is related to the question?
        · Remember that the activity of an enzyme is directly related to its structure and function. Recall that there are several structural elements of an enzyme that affect its function; these include the active site and the allosteric site. These structural elements as well as inhibitors influence an enzyme’s ability to facilitate reactions. The question also indicates that the drug acts as a competitive inhibitor of the enzyme. Considering the structure and function of enyzmes, which most directly affected by bacterial drug resistance that reduces enzyme activity?

  Choose Answer
Do you have all necessary information to analyze how drug resistance would reduce enzyme activity?  
        · The first major clue in this question is that the drug is a competitive inhibitor of the enzyme, and that microbial changes in the enzyme’s structure render the drug ineffective. Recall that competitive inhibitors mimic the shape of a substrate, which binds to the active site. This information implies that the shape of the drug was a close match to the substrate in order to be competitive inhibitor in the first place.
        · A second major clue is the mutation in the bacterium that also renders the drug ineffective.
        · These two lines of evidence imply that the active site of the enzyme must be directly involved, since neither the allosteric site nor the activation energy of the enzyme would be affected.

  Reflect on Process
Did your problem-solving process lead you to the correct answer? If not, where did the process break down or lead you astray? How can you revise your approach to produce a more desirable result?
        · This question asked you to analyze possible reasons for why a previously-effective drug that works as a competitive inhibitor is rendered ineffective by bacterial mutation.     
        · If you got the answer correct, well done! If you got an incorrect answer, were you able to break down the structural elements of the enzyme into the active and allosteric sites? Were you able to correlate the two lines of evidence of the drug being a competitive inhibitor and the bacterial mutation eliminating drug effectiveness? Were you able to infer from this evidence that the active site was the most likely aspect of the enzyme to be affected?