Uridine Monophosphate Synthetase - Structure and Function

Structure and Function

This bifunctional enzyme has two main domains, an orotate phosphoribosyltransferase (OPRTase, EC 2.4.2.10) subunit and an orotidine-5’-phosphate decarboxylase (ODCase, EC 4.1.1.23) subunit. These two sites catalyze the last two steps of the de novo uridine monophosphate (UMP) biosynthetic pathway. After addition of ribose-P to orotate by OPRTase to form orotidine-5’-monophosphate (OMP), OMP is decarboxylated to form uridine monophosphate by ODCase. In microorganisms, these two domains are separate proteins, but in multicellular eukaryotes, the two catalytic sites are expressed on a single protein, uridine monophosphate synthetase.

UMPS exists in various forms, depending on external conditions. In vitro, monomeric UMPS, with a sedimentation coefficient S_20,w of 3.6 will become a dimer, S_20,w = 5.1 after addition of anions such as phosphate. In the presence of OMP, the product of the OPRTase, the dimer changes to a faster sedimenting form S_20,w 5.6. These separate conformational forms display different enzymatic activities, with the UMP synthase monomer displaying low decarboxylase activity, and only the 5.6 S dimer exhibiting full decarboxylase activity.

It is believed that the two separate catalytic sites fused into a single protein to stabilize its monomeric form. The covalent union in UMPS stabilizes the domains containing the respective catalytic centers, improving its activity in multicellular organisms where concentrations tend to be 1/10th of the separate counterparts in prokaryotes. Other microorganisms with separated enzymes must retain higher concentrations to keep their enzymes in its more active dimeric form.