Figure 3.

Proposed model of reaction-driven imidazole ring flip mechanism in serine hydrolases containing the catalytic triad. Shaded species are unproductive. Relative abundance of imidazole rotamers represented only qualitatively by magnitudes of double arrows, so arrow lengths should not be interpreted literally. The mechanism requires only an increasing trend in the flipped/normal ratio in moving from resting enzyme to TI-1 to acyl enzyme. See supplementary material for an animated video loop with sound effects.