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?

Explanation:

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.

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