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

Abstract

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 180Gly-Gly190 were removed and Arg203 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.