Question

Two antibiotics, A and B, alter the activity of peptidoglycanase, an enzyme used to synthesize cell walls in bacteria. One acts through competitive inhibition, the other through non-competitive inhibition. What is the difference between these two mechanisms of control? Which antibiotic would the bacteria be more likely to develop resistance against? Why?

Answer 1

Mechanism of competitive inhibition:
This kind of antibiotic inhibits the enzyme by resembling their structure with the substrate and binds directly to the active site of the enzyme, involving reversible and non-covalent interactions with the enzyme. So when the concentration of antibiotic is more than the concentration of the actual substrate of the enzyme, antibiotic will bind to the active site of the free enzyme and will not allow the substrate to bind. Hence, the enzyme-substrate complex will not form and no product will be formed.

Mechanism of Non-competitive inhibition
The antibiotic which inhibits the enzyme activity by non - competitive inhibition, needs not to resemble the structure of the substrate because it does not inhibit by binding to the active site of the enzyme. These kinds of antibiotics bind to the site other than the active site and can bind to either the free enzyme or even to the enzyme-substrate complex. Binding of the antibiotic will change the 3-D conformation of the enzyme, changing the structure of the active site. Hence, either it will not allow the enzyme-substrate complex to form or if it will form, at a very slow rate eventually leading to inhibition of product formation. Most of the non-competitive inhibitors bind irreversibly to the enzyme mainly by covalent interactions and are found to be more effective.
This is how any antibiotic which inhibits the enzyme by non-competitive inhibition will inhibit the enzyme peptidoglycanase.

Below picture helps you to understand better

The antibiotic which inhibits the enzyme by binding to the active site that is, which inhibits competitively will let the bacteria to develop resistance against it easily because bacteria will after some time will change the structure of the enzyme in a way to not allow the antibiotic to bind to it by mutations and also bacteria will eventually be forced to produce an enzyme which will inactivate the antibiotic by binding to it irreversibly.
This will not occur in the case of non-competitive inhibition because antibiotic does not bind directly to the active site of the enzyme.

Hope this will help you