Orotidine 5'-phosphate decarboxylase

OMP decarboxylase has been a frequent target for scientific investigation because of its demonstrated extreme catalytic efficiency and its usefulness as a selection marker for yeast strain engineering.

To put this in perspective, the uncatalysed reaction which would take 78 million years to convert half the reactants into products is accelerated to 18 milliseconds when catalyzed by OMP decarboxylase.

(See figure of enzyme bound to BMP) Several mechanisms for enzymatic decarboxylation of OMP have been proposed, including protonation at O2 to form a zwitterionic species as an intermediate,[6] anion stabilization of O4,[7] or nucleophilic attack at C5.

This mechanism was suggested from studies investigating kinetic isotope effects in conjunction with competitive inhibition and active site mutagenesis.

This bifunctional enzyme is named UMP synthase and it also catalyzes the preceding reaction in pyrimidine nucleotide biosynthesis, the transfer of ribose 5-phosphate from 5-phosphoribosyl-1-pyrophosphate to orotate to form OMP.

Schematic of reaction catalyzed by OMP decarboxylase
Image representing the structure of the active site of OMP decarboxylase when bound to the inhibitor BMP. Note the Lys and Asp residues surrounding the 6-hydroxyl of the substrate. (Image captured from pymol viewer snapshot of 1LOR crystal structure) [ 5 ]
Reaction schematic showing the mechanism of OMP decarboxylase catalysis through a putative vinyl carbanion at the C6 position. This carbanion is likely stabilized by the nearby protonated lysine residue. The Lys93 and Asp91 residue numbering corresponds to the sequence for OMP decarboxylase from S cerevisiae. [ 13 ]