Why is that a higher affinity leads to increased effectiveness of a drug inhibitor?
Also, most importantly why do enzymes bind more tightly to transitions state analog inhibitors?
what is stickase?? and why are people's explanations using a bent 'rod stick' as an example
Hi there,
The answer is because enzymes wouldn't be enzymes if they wouldn't be able to stabilize the transition state in order to increase the rate of the reaction (by lowering the energy barrier between substrates and products and therefore by increasing the probability to get over this energy barrier). The theory of abzymes (catalytic antibodies) has proved that this higher affinity for the transition state is absolutely required for antibody to exhibit significant catalytic activity. The fact that transition state analogs are generally good inhibitors just validate the fact that enzymes binds tightly the transition state. The stickase example is only made to show that transition state is structuraly different from both substrate and product.
Enzymes are catalysts. Catalysts accelerate reactions by lowering the activation energy barrier between reactants and products. The transition state is the state with the highest energy along the reaction coordinate. By binding with the highest affinity to the transition state, the enzyme lowers the free energy of the transition state, thereby reducing the activation energy.
Here is a wiki article on the subject:
https://en.wikibooks.org/wiki/Structural_Biochemistry/Enzyme/Transition_state
Following paper will help you to get a clearer concept:
http://www.utdallas.edu/~son051000/comp/TS_Schramm.pdf
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