Steve Ealick's Research Group

Orotidine 5′-Monophosphate Decarboxylase

PDB file: 1DBT


Orotidine 5′-monophosphate decarboxylase(OMPDC) is the most proficient enzyme that has yet been analyzed. It functions without a cofactor to facilitate the final step in the de novo biosynthesis of uridine monophosphate. X-ray crystallographic studies caused us to discard three prior proposed mechanisms for the enzyme's action. Instead, we proposed an unprecedented SE2mechanism to agree with the observed structural and kinetic data.

The monomer unit of the enzyme utilizes a triose phosphate isomerase (TIM) barrel fold.
Note the bound uridine monophosphate product in the active site.


Click the image to enlarge.

The active form of the enzyme is a dimer of identical subunits, which exhibit an extensive set of contacts between twofold related TIM barrels. This rotation places the top of each barrel in close contact to each other.

The active site is located at the end of a barrel near the interface of the two monomers.
Note the bound uridine monophosphate product in the active site.


Click the image to enlarge.

About 18 residues line the active site cavity, so the active site stretches nearly across one end of the barrel. Of the active site residues, 15 are contributed by one monomer and three by the adjacent monomer. Click here to see a schematic representation of the active site. Only charged and hydrophilic residues are included. Hydrogen bonds are shown as dashed lines.


Appleby TC, Kinsland C, Begley TP, and Ealick SE. The crystal structure and mechanism of orotidine 5′-monophosphate decarboxylase. Proc. Nat. Acad. Sci. USA 97:2005 (2000).

This work was also featured in an article in Chemical and Engineering News:

Rouhi AM. The buzz about a remarkable enzyme. C&EN 78:42-46 (2000).

The OMPDC Team

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