FIGURE 3.

A diagram illustrating the distribution of conformational sub-states as a function of temperature in ht-ADH. Reproduced with permission from Ref. 40, copyright (2011) National Academy of Sciences, U.S.A. a–c indicate the redistribution of enzyme from an inactive region of the conformational landscape (state 4) into the regions that can support hydride transfer (states 1-3) as the temperature is raised above 30 °C. The mathematical model treats the rate as a function of a temperature-dependent equilibration, K_eq, and the rate constant, k_intrinsic. d shows the ability to achieve A_observed = 10²⁵ s⁻¹ via a compensatory increase in ΔH^‡ and TΔS^‡. The extrapolation to A_intrinsic is shown by the dashed line, and the extrapolation to A_observed is shown by the solid line.