Question

Imagine there is an enyzme that is critical for the progression of the viral disease Dramatic Chipmunk has. (Note: it is irrelevant which specific viral disease Dramatic Chipmunk has). Scientists know the substrates, products, and a chemical mechanism for this enzyme, but there are no known inhibitors. If an organic chemist is asked to synthesize some inhibitors, they will almost always try to make competitve inhibitors for it. However, if a natural product chemist was asked to look for enzyme inhibitors in libraries of molecules isolated from plants/fungi, they will likely find that competitve, mixed and uncompetitive inhibitors all exist in nature in fairly equal amounts.

Why does the organic chemist synthesize competitive inhibitors alone when any other kind of inhibitor would be just as good? Is there a scientific reason most organic chemists don't try to synthesize mixed/uncompetitive inhibitors? Explain your answer.

Answer 1

The competitive inhibitor binds the same active site of the enzyme where the substrate binds. The mechanism is reversible, that is, if the concentration of the substrate is increased, the inhibition is reversed. The Vmax of the reaction remains unaltered.

In case of noncompetitive inhibitors, it binds to an allosteric site, which is not the binding site for the substrate. Therefore, the conformational change induced by allosteric binding decreases enzyme efficiency. It decreases the rate of reaction. Uncompetitive inhibitor binds only to the enzyme-substrate complex. It makes the substrate/prodcut bound to the enzyme for a longer time period and thus decreases the efficacy of the enzyme.

Organic chemists try to synthesize competitive inhibitors since it is easy to predict the structure of the inhibitor based on the structure of the substrate. Since both bind to the same location, some initial idea about the structure of the substrate provides insights for what should be the structure of the inhibitor. However, this could not be done for other inhibitors as the structure of binding sites cannot be predicted that easily.