Figure 3.

Representation of 2D Energy landscape of TLL diffusional states sampling and its biasing by regulatory cues and lid mutations. (A) Cartoon representation of free energy landscape based on functional states, for the native enzyme and L2 shows the three distinct sampled states and the energy barrier between them, as well as the forbidden states within our experimental time frame. (see Table S3, Fig. S10 for all rates). (B) State occupancies for all lipase mutants and their dependence on environmental regulatory cues and mutations. The fast mode is only observed in the highly active native and L3 variants. Intermediate activity variant L2 or product inhibitions, operate via eliminating sampling of the fast diffusional and sampling of an intermediate state instead. (C) Model with native TLL diffusional states displaying the microscopic transition rates and its redistribution by product inhibition (see Fig. S12 for all conditions). Product Inhibition of TLL operates by rerouting conformational sampling pathways.