Thioester Hydrolysis and CC Bond Formation by Carboxymethylproline Synthase from the Crotonase Superfamily

Enzyme in action: Labeling studies and the finding that carboxymethylproline synthase catalyzes production of deuterated (2S,5S)-6,6′-dimethyl-trans-carboxymethylproline (3) from dimethylmalonyl-CoA (1) and labeled l-pyrroline-5-carboxylate (2) limit possible mechanisms of CC bond formation and thioester hydrolysis. A key feature in the catalysis is that intermediates are stabilized by hydrogen bonds in the “oxy-anion hole” of the enzyme (dark curve in scheme).