Figure 7.

Proposed mechanism of Schiff base formation. (a) DHQD adopts an open loop conformation in the absence of ligand. (b) DHQ binds to the open loop conformational state, as observed in protomer B of the shikimate complex. (c) Closure of the loop requires Arg213 and DHQ to shift deeper into the active site. The presence of Lys170 in the wild-type enzyme sterically disallows the K170M binding mode (black box), forcing the DHQ 3-carbonyl to pivot away from Lys170 and generating a prenucleophilic attack state like that described by Pan et al.²¹ (d) The reactive carbonyl is positioned at a stereoelectronically reasonable nucleophilic approach angle in the prenucleophilic attack state that allows reaction with Lys170 to generate the Schiff base intermediate.