Orotidine 5′-monophosphate decarboxylase catalyses the decarboxylation of orotidine 5′-monophosphate to uridine 5′-monophosphate (UMP) without the aid of any metal ions or cofactors. This reaction is the last step in the de novo synthesis of pyrimidine nucleotides.
We have determined an apo-structure of orotidine 5′-monophosphate decarboxylase from Vibrio cholerae. Two chains of the protein in the asymmetric unit form a closely bound homodimer. Each subunit of the dimer folds as an alpha/beta-barrel with eight central beta-strands flanked by eleven alpha helices. There is one active sites per subunit located at the C termini of the beta-strands of the barrel. Residues from both chains contribute to formation of each active site. A conserved unique motif Lys-Asp-Lys-Asp of the active site is present in the V. cholerae decarboxylase. Structures of binary complexes with UMP and known inhibitor 1-(5′-phospho-beta-D-ribofuranosyl)barbituric acid (BMP) can help to elucidate the mechanism of the reaction catalyzed by the protein.