The transition state inhibitors are the inhibitors that resemble the transition state of an enzyme catalyzed reaction. It binds to the active site more strongly than either the substrate or the product using non covalent forces.
In HIV (Human immunodeficiency virus) protease catalyzed reaction, a nucleophilic mechanism is followed for the hydrolysis of peptide bond between neostigmine. This results in the formation of the bond with the carbonyl group. Further leads to the formation of an unstable intermediate that comprises of the tetrahedral center. The characteristics of the transition state inhibitor should be similar to the intermediate.
The similarities in Structure of neostigmine (Transition state inhibitor) to the HIV protease catalyzed reaction intermediate are as follows:
1. The tetrahedral centre bearing the alcohol group should be present in the intermediate.
2. The stability to the structure is provided by the presence of extra methylene group between the proline and tetrahedral center.
The above mentioned features make Structure of neostigmine fit the description of a Transition State Inhibitor. An IC50 6500 nM (nanomolar) means that the concentration of inhibitor required to inhibit the enzyme by 50% is 6500 nM. Lower the IC50 value, more potent the inhibitor.