2014 Volume 56 Issue 4 Pages 236-240
Crystallographic investigation combined with QM/MM simulation and biochemical analysis is the powerful tool to elucidate the enzyme mechanisms. Here, orotidine 5'-monophosphate decarboxylase (ODCase) is selected as a representative example of intensively investigated enzymes. This enzyme accelerates the conversion of orotidine 5'-monophosphate into uridine 5'-monophosphate by 17 orders of magnitude, and is known as one of the most proficient enzymes. Although the decarboxylation reaction is an electrophilic-like reaction, ODCase also catalyzes nucleophilic-like reactions at the same catalytic site with the decarboxylation. Our crystallographic analysis at 1.0−1.8 Å resolution combined with ab initio calculation and biochemical assays elucidated the catalysis of ODCase utilizes the substrate distortion in addition to the transition state stabilization.