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.
Wu
Ning
N
Department of Biochemistry, University of Toronto, Ontario M5S 1A8, Canada.
Pai
Emil F
EF
D019943:Amino Acid Substitution; D001665:Binding Sites; D018360:Crystallography, X-Ray / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D017014:Methanobacterium / Q000201:enzymology*; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D009964:Orotidine-5'-Phosphate Decarboxylase