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?

The fact that these mutated drugs work as inhibitor of specific enzymes shows that they operate based on enzyme mechanism of enzyme-substrate complex. Therefore the drugs must have an active sites which fits in perfectly to the substrate to undergo competitive inhibition with specific enzyme forming enzyme-substrate complex in the microbes.

Thus if these drugs failed to bind with substrates for competitive inhibition with specif enzymes, in the microbes, definitely the active active site of these drugs is affected by the mutation. Thus the drugs have lost the specificity for binding with specific enzymes; disrupting the enzyme-substrate complex during drug reactions leading to loss of drug potency, and rise in resistance

Generally the specificity of an enzyme depends on the 3-Dimensional tertiary structure of the active sites. Any alteration in the 3 - Dimensional shape of the active site renders the enzyme inactive and non specific. Therefore loss of shape of active sites in the drugs to mutation leads to loss of specificity of the drugs for enzymatic reactions, and thus loss of activity, and increase in drug resistance by microbes.