Crystal structures of inhibitor complexes reveal an alternate binding mode in orotidine-5'-monophosphate decarboxylase.

The crystal structures of the enzyme orotidine-5'-monophosphate decarboxylase from Methanobacterium thermoautotrophicum complexed with its product UMP and the inhibitors 6-hydroxyuridine 5'-phosphate (BMP), XMP, and CMP are reported. A mutant version of the protein, in which four residues of the flexible phosphate-binding loop (180)Gly-Gly(190) were removed and Arg(203) was replaced by alanine, was also analyzed. The XMP and CMP complexes reveal a ligand-binding mode that is distinct from the one identified previously with the aromatic rings located outside the binding pocket. A potential pathway for ligand binding is discussed.