Figure 1: Allosterism and inhibition.
(A) Allostery offers several major advantages over orthostery. Whereas both allostery and orthostery offer potency (IC50) for regulating inhibition, allostery (especially partial allostery) offers efficacy (% ΔY) in addition for controlling protease inhibition. (B) Thrombin, a soluble monomeric protease, is a highly plastic enzyme that displays multiple conformational isoforms in its ground state19,21,57. These conformational forms, labeled 1 through 4, are in equilibrium, which can theoretically be enriched through small molecules that bind at an allosteric site. Such allosteric agents may display partial inhibition of the protease at saturation, a phenomenon not known for monomeric proteases.
