Structural and mechanistic studies of Trypanosoma brucei ornithine decarboxylase.

Ornithine decarboxylase (ODC) is a pyridoxal-5'-phosphate (PLP)-dependent enzyme that catalyzes the first committed step in the biosynthesis of polyamines. The polyamines are ubiquitous cell growth factors and the biosynthetic enzymes have been of interest as potential drug targets for the treatment of proliferative diseases. X-ray structural analysis of the eukaryotic ODCs shows that the enzyme is a homodimer with two identical active sites that are formed at the dimer interface. A number of active site residues have been identified that have similar mechanistic roles to the analogous residues in other PLP-dependent enzymes, whereas others provide the basis for the reaction and substrate specificity required by ODC.