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Model for different binding sites of GSMs and GSIs. The active site of γ-secretase is represented by a pair of scissors. GSMs alter the “handle” of the scissors, thereby manipulating the way the enzyme cuts and/or the location of the cleavage sites. In contrast, an allosteric GSI will shut the blades, whereas a transition state analog (TSA) will block the blades of the scissors, preventing substrate binding and cleavage of the substrate.
